Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel
© Burlina et al; licensee BioMed Central Ltd. 2011
Received: 15 November 2010
Accepted: 27 May 2011
Published: 27 May 2011
Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen.
An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain.
We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients.
Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate.
KeywordsDiagnosis Fabry Disease Neuropathy Pain Treatment
Possible early symptoms of Fabry disease
Reduced quality of life; reduced well-being; reduced school/work performance and engagement in leisure activities, including sports
Psychosocial and behavioral deficits
Poor weight gain
Chronic burning pain
Attacks of excruciating pain
Abdominal cramp, (post-prandial) diarrhoea, bloating, nausea
Tinnitus, hearing loss
Vascular lesions (angiokeratoma, Figure 1)
Corneal/lenticular opacities (seen on slit lamp examination, Figure 2)
Vascular tortuosity (retina, conjunctiva)
Impaired concentration ability
Increased urinary GL-3 excretion
Renal hyperfiltration (early), decrease in glomerular filtration rate
ECG abnormalities (for example, short PR interval)
Arrhythmias, hypertrophic cardiomyopathy (young adults)
The first neurologic symptoms reflect damage to the small fibers of the peripheral and autonomic nervous systems. Peripheral neuropathic pain in young patients with Fabry disease can manifest as chronic, burning pain and superimposed attacks of acute excruciating pain (described in more detail later), dysesthesias, thermal sensation deficits (primarily cold perception), and paresthesias (e.g., painless tingling) [12–14]. Symptoms related to autonomic nervous system dysfunction may include hypohidrosis, impaired pupillary constriction and saliva and tear production, gastrointestinal dysmotility (abdominal cramping pain, bloating, diarrhea, nausea), and sensory losses.
Luminal encroachment and occlusion of the vasa nervorum of the peripheral nerves due to endothelial GL-3 storage, disturbed balance between vasodilatative and vasoconstrictive mechanisms, and thrombotic complications are factors that may contribute to ischemic neural damage [28, 29]. Also, GL-3 accumulation in skin cells may interfere with the function of intradermal sensory receptors.
Although still insufficiently understood, peripheral nerve injury may induce a variety of peripheral and central mechanisms, e.g., axonal sensory hyperexcitability, ectopic spontaneous firing, and central sensitization that have been described elsewhere [12, 13, 30, 31]. The extent of overlap of these mechanisms in the various stages of Fabry disease is uncertain.
An International Expert Panel on Neuropathy in Fabry Disease convened on January 12th, 2009, in Rome, Italy. The Panel was composed of 8 experts (7 physicians/physician scientists, 1 scientist) in the area of Fabry disease and/or peripheral neuropathy from the US, Canada, South America, and Europe. The aim of the meeting (sponsored by Genzyme Corp.) was to develop guidance on the clinical evaluation of early stages of small fiber neuropathy in Fabry disease, focusing on simple diagnostic tools that can be quickly applied by the practitioner, and on treatment of the neuropathic pain. The recommendations are supported by a review of relevant medical literature published up to September 2010. Given the well manageable number of relevant publications, no specific criteria for literature review were used. Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate .
Clinical course of neuropathic pain in Fabry disease
Burning, nagging pain with a symmetric distribution pattern in the palms of the hands and soles of the feet of children or adolescents and peripheral dysesthesias are the first symptoms to raise alarm. Recurrent attacks of pain ("pain crises"), described as "excruciating", "agonizing", "lightning" or "stabbing" pain, often begin in the distal parts of the extremities and may radiate proximally [12, 32]. They can be so intense that the patient is confined to bed , and episodes can occur daily . They may be triggered by a rapidly changing core body temperature (e.g., fever, stress, physical activity) presumably due to a decreased ability to sweat [12, 32], although they have been noted even in patients with hyperhidrosis . Additional triggering factors include sudden exposure to cold, rapid changes in humidity, and fatigue . Deep ache, significant joint pain, bouts of unexplained fever, and elevated erythrocyte sedimentation rate can accompany a pain crisis [12, 35, 36].
Neuropathic pain was reported by ~60 and 80% of the affected boys enrolled in the two Fabry disease registries, usually beginning in childhood, and by ~40 to 60% of affected girls, often a few years later than in boys [1, 2]. Most adult males and 60 to 90% of females experience some form of Fabry pain [13, 37–39]. Over time, neuropathic pain appears to diminish, perhaps due to progressive loss of nerve fibers, but can also become more severe [40, 41].
It has recently been proposed to abandon the use of "acroparesthesia" in the description of Fabry neuropathic pain because, by definition, paresthesias are painless tingling sensations . In fact, paraesthesias appear to be rather uncommon in Fabry disease as they were reported by only ~10% of affected adults .
In children with Fabry small fiber neuropathy, reductions in feelings of well-being and in school attendance and a reluctance to participate in sports, gymnastics, and leisure activities are of particular concern. As the patient ages, the symptoms lead to increasing neurological disability and impairment of quality of life in both males and females [7, 10, 43–45].
As in other conditions with chronic neuropathic pain, pain medication dependence (e.g., opioids) and substance abuse can occur . Patients may develop social-adaptive or psychological functioning deficits [47, 48] and many become depressed, with the presence of neuropathic pain being the strongest predictor of depression . Suicidal ideation has been reported in patients with Fabry disease [49–51].
Small fiber dysfunction in Fabry disease
The pattern of small fiber dysfunction in Fabry disease is seen in various other diseases characterized by peripheral neuropathy, including diabetes mellitus [52, 53]. However, if provoked crises of excruciating pain occur, the diagnosis of Fabry disease should be highly suspected. The neuropathy in Fabry disease is a length-dependent neuropathy [12, 54] typically associated with a marked reduction of thinly myelinated Aδ fibers (mediating sharp pain, cold perception), unmyelinated C fibers (pain, warmth perception), and loss of unmyelinated autonomic fibers [17, 19, 21, 23, 24, 40, 55–59]. Female patients, even when asymptomatic, may also be affected by loss of small fiber function [39, 54, 60].
Disappearance of pain may not necessarily reflect nerve recovery but rather degeneration of nerve fibers and the sensory neuropathy may progress to numbness and hypoalgesia. Recently, an association between the severity of small fiber neuropathy, determined by cold perception in the feet, and progressive sensorineural hearing loss has been reported, both in male and female patients .
Autonomic small fiber damage in Fabry disease is likely to be related to the patients' gastrointestinal dysmotility (e.g., abdominal cramps, bloating, diarrhea, nausea), hypohidrosis, impaired pupillary constriction, decreased tear and saliva formation, Raynaud phenomena, sensory losses, reduced heart rate acceleration upon exercise and, in advanced stages, orthostatic hypotension [17, 37, 66]. The cutaneous response to scratch can be diminished [17, 67], and baroreflex-mediated vasoconstriction can be deficient due to sympathetic vasomotor nerve fiber dysfunction .
Pancreatic parasympathetic dysfunction may cause post-prandial diarrhea after consumption of a high-fat meal . Both autonomic sudomotor nerve fibers and sweat gland function are impaired in untreated patients [37, 70]. Hyperhidrosis can also be recognized in patients with Fabry disease, mainly in females. If present, it often manifests in childhood or adolescence .
Of note, the generally accepted assumption that autonomic neuropathy plays an important role in the pathophysiology of Fabry disease has recently been questioned by one group of investigators . The observation of nearly normal male sexual function and autonomic control of the cardiovascular system in patients with Fabry disease led the investigators to suggest that end-organ damage, rather than autonomic dysfunction, might play a prominent role in Fabry disease.
Large fiber dysfunction in Fabry disease
As large Aα and Aβ fiber modalities (e.g., motor function, position, and vibration sensation) are generally spared in early stages of Fabry disease, it is not surprising that the results of motor and sensory nerve conduction tests have mostly been normal [19, 21, 34, 36, 40, 57, 61, 66, 72, 73]. With progression of the disease, however, large fiber involvement with associated nerve conduction abnormalities may develop. Reductions of compound muscle action potential amplitudes are seen more often than the slowed conduction velocities . Impaired vibration perception may be a consequence of disturbed transmission of the synchronized impulse volleys in large myelinated afferent Aβ fibers, or by GL-3-induced dysfunction of intradermal corpuscles (mainly Pacinian corpuscles and Meissner bodies [74, 75]) mediating the vibratory stimuli [40, 73]. With age, more severe abnormalities involving large fibers are expected to occur as demonstrated by a significant influence of age on vibratory perception .
The mechanisms contributing to development of large nerve fiber abnormalities in a subset of patients are as yet unclear. It has been suggested that Schwann cell pathology due to GL-3 accumulation might account for slowing of conduction velocities . Uremia due to Fabry end-stage renal disease and overuse of alcohol may add to the large fiber pathology [40, 55, 66, 76].
Median nerve conduction abnormalities may indicate median nerve entrapment caused by GL-3 accumulation in carpal tunnel structures. A prevalence of carpal tunnel syndrome of ~25% has been reported for both male and female patients with Fabry disease [36, 55].
Diagnosis and simple assessments
The early neurologic manifestations of Fabry disease are initially often subtle and affected children are frequently misdiagnosed as having rheumatism, viral infection, growing pains, "bone problems", psychogenic pain, cryptogenic pain, food intoxication, or non-specific gastrointestinal pain . Although first symptoms appear in childhood, correct diagnosis may be delayed until well into adulthood. Data from the Fabry Registry shows that the mean diagnostic delay was approximately 11 years for both genders . While still undiagnosed and untreated, the disease increasingly impairs the young patient's well-being.
Medical history and examinations in young patients with Fabry disease
Decreased stamina and exercise; psychologic co-morbidities; school, work and sport participation and performance; smoking
SF-36® Health Survey or PedsQL™
Onset; quality; intensity; distribution; abnormal responses to stimuli; exacerbating factors; pain meds (past, current), McGill Pain Questionnaire, Brief Pain Questionnaire, Pediatric Pain Questionnaire
Abdominal cramps; (post-prandial) diarrhea; number of bowel movements/day; bloating; nausea
Renal/cardiac failure; TIA or stroke; early death
Complete physical examination
Including height; weight; pulse irregularity; supine and standing blood pressure; vascular skin lesions (Figure 1); cornea clouding (requires slit lamp exam, Figure 2)
Thermal perception (cold/warm water tubes, a cold and warm tuning fork or reflex hammer, or thermal discs at dorsal foot, e.g., "Minnesota Thermal Disks" )
Pain perception (pinprick to skin of limbs and trunk)
Light touch perception (cotton swab or lightly touching skin, e.g., on legs vs. feet, testing distal vs. proximal sensation)
Vibration perception (vibrating tuning fork (Rydell-Seiffer®) to 1st metatarsal bone)
Sensorineural hearing loss (Rinne test, three-tone audiometry)
α-Galactosidase A enzyme activity in leukocytes or whole blood in males
GLA mutation analysis in females (known family mutation testing or full gene sequencing)
Genetic risk assessment
Diagnosis should be followed by genetic testing of the entire family
A neuropathy pain assessment scale should be used at the initial assessment and follow up examinations. The Neuropathy Symptoms and Change Questionnaire evaluates the number, severity and change of symptoms, as well as motor, autonomic, large fiber and small fiber sensory nerve function . Other available neuropathic pain evaluation tools include the Leeds Assessment of Neuropathic Symptoms and Signs, Neuropathic Pain Questionnaire, Neuropathic Pain Symptom Inventory, Douleur Neuropathique en 4 questions, pain DETECT, and ID-pain . The Total Symptoms Score has been used for grading of neuropathic pain in clinical studies in diabetes and Fabry disease patients with peripheral neuropathy [73, 80].
The patients can also be asked to keep a (weekly) pain diary. A more general pain assessment can be performed by using, for example, the Pediatric Pain Questionnaire or the McGill Pain Questionnaire. The quick version, the Short-form McGill Pain Assessment Questionnaire , is particularly easy to administer. Quality of life can be assessed by using the Short Form-36 (SF-36®) Health Survey (http://www.sf-36.org) or Pediatric Quality of Life Inventory (PedsQL™) .
A complete physical examination should be performed as it may provide clues to the diagnosis of Fabry disease (Table 2). It should include measurement of height and weight, heart rate (irregular pulse) and supine and standing blood pressure to determine orthostatic hypotension (defined as a drop in systolic blood pressure by at least 20 mmHg, or in diastolic blood pressure by at least 10 mmHg, within the first three minutes upon active standing up from the sitting or supine position, or upon passive head-up tilt) . The skin should be inspected for presence of vascular skin lesions (angiokeratoma, Figure 1), particularly in the bathing trunk area. Cornea verticillata (Figure 2) is readily detectable by slit lamp examination and present in almost all males and 70% of females with Fabry disease [32, 84]. Routine blood work-up is usually normal. Albuminuria may be detected in young patients and is an antecedent to progressive Fabry nephropathy .
The neurologic examination in children, adolescents and young adults should focus on sensations mediated by peripheral small fibers, as overt central nervous system involvement is usually not yet present (Table 2). Relevant, easy to perform and non-invasive sensory perception tests include cold, heat, light touch, pinprick, pressure and vibration perception testing. Assessment of allodynia and hyperalgesia should preferably be carried out in the area of maximal pain. All tests should be performed under comfortable ambient conditions and temperature at the distal lower limbs.
Early in the course of small fiber neuropathy, impaired appreciation of thermal stimuli primarily involves cold perception rather than warm perception [39, 62]. A rather crude test of thermal perception consists of placing tubes filled with cold and warm water, a cold and warm tuning fork, the handle of a reflex hammer, or thermal discs with a polyvinyl surface on one side and a metal surface on the other side (similar to the "Minnesota Thermal Discs" ) on the patient's foot. Cold sensation can also be assessed by using acetone spray, or by immersing one leg up to the mid thigh (or one forearm) for 30 seconds into ice-cold water . Normal subjects report little discomfort to a brief immersion of a limb in ice water, but the Fabry patient experiences intense burning pain within 10-30 seconds.
Pain perception and hyperalgesia can be tested by applying just enough pressure with a sharp pin to indent the skin. Loss of discrimination between pinprick sensation and application of a blunt pressure sensation points towards small fiber neuropathy.
Perception of light touch and mechanical allodynia can be tested by lightly rubbing the skin with a cotton swab or by lightly squeezing the patient's leg. Vibration can be assessed by placing a scaled (8/8), vibrating 128 Hz tuning fork to the first metatarsal bone .
Symmetrical sensorineural hearing loss can be explored by performing the Rinne test. The stem of a vibrating tuning fork (512 or 256 Hz) is placed on the mastoid process until sound becomes inaudible; the fork is then immediately placed outside the ear. In case of sensorineural hearing loss, bone conduction and air conduction are both equally reduced. However, to reliably assess or rule out hearing loss, three-tone audiometric testing needs to be performed .
Abnormal results of the tests described above may lead to more comprehensive examinations trying to document the sensory abnormalities qualitatively and quantitatively. A standardized quantitative sensory testing (QST) protocol to assess the somatosensory profile within 30 minutes and diagnose a small fiber neuropathy is available [53, 56, 89]. The QST battery consists of 7 tests measuring thermal detection, thermal pain and mechanical detection thresholds and mechanical pain sensitivity. An abbreviated version of this protocol assessing cold and warm detection thresholds can be applied within approximately 10 minutes and may facilitate the development of new screening strategies for Fabry disease. Methods to test nerve conduction velocities, sympathetic skin response, quantitative sudomotor axon reflex sweating, saliva and tear formation, and other autonomic dysfunction are not further discussed in this manuscript that focuses on simple bedside tests. Given the availability of an accurate diagnostic laboratory test, nerve or skin biopsies are not required for diagnosing Fabry disease, although skin biopsy can detect small fiber disease in yet asymptomatic patients and may be used to quantify loss of skin innervation .
Measuring α-galactosidase A enzyme activity in leukocytes is the gold standard assay of diagnosis of Fabry disease in males . Many females with Fabry disease, however, may have enzyme activity levels within the normal range. Diagnosis in females, therefore, requires genetic studies to detect or confirm the Fabry mutation. Extended familial assessment identified, on average, five family members with Fabry disease for every proband . Therefore, the importance of taking a family history and genetic testing in all members of the family of a newly identified patient cannot be underestimated.
Evaluation and monitoring of the small fiber neuropathy are important as the elicited signs and symptoms may provide insight into possible pathophysiological mechanisms and, in turn, may provide guidance on optimal pain management. Given the progressive nature of Fabry disease, regular objective and comparable monitoring of the neuropathy and its progression using reproducible measures of staging is required for therapy adjustment. Particularly useful may be the neuropathy staging scheme developed by Dyck  as it scores sensory, autonomic, and motor components separately, and provides an overall stage. Other available methods to score severity include the Total Symptom Score for grading of pain [73, 80], and the Neuropathy Impairment Score .
Current management of pain in pediatric patients with Fabry disease appears to be inadequate. This is as illustrated by the fact that the majority of children in the Fabry Registry who had neuropathic pain reported not to have received any pain medication .
Given the episodic and provoked nature of many of the painful crises, it should be emphasized that identification of individual provocateurs is important for conservative management. Patients can change their lifestyle and take preventive measures to avoid exposure to, for example, rapid changes in temperature. The goal of pharmacological management of neuropathic pain should be to decrease pain to a tolerable and functional level and, thereby, to improve the patient's quality of life, activities of daily life, and psycho-social function.
We are not aware of any randomized controlled trial of an analgesic for the treatment of painful peripheral neuropathy in Fabry disease; only some empiric use of drugs has been reported [93–95]. However, a substantial body of evidence exists for the treatment of other types of painful neuropathy and this may serve as a guide for the physician treating the Fabry disease patient [96–99]. Pain treatment should generally consider the most likely mechanism in each case. However, in the attempt to achieve optimal pain management, multiple medications targeting different aspects of the complex pathways might be considered in patients with advanced disease. It is recommendable to start pain medication(s) at low dose, and to evaluate the tolerability and effectiveness of a change in medication(s) after 2-3 weeks.
Anticonvulsants are commonly used to reduce pain in neuropathic pain disorders, including diabetic neuropathic pain [96–99]. Carbamazepine alone , or in combination with pregabalin (rather than gabapentin) , is recommended as first-line treatment in Fabry neuropathic pain. Symptoms suggestive of autonomic dysfunction should be monitored as dose-dependent exacerbation of autonomic dysfunction has been reported . Antidepressants, particularly dual reuptake inhibitors of both serotonin and norepinephrine (SNRIs; venlafaxine, duloxetine; black-box warning for use in pediatric age group) are also viable options. Because of their anti-cholinergic effect, tricyclic anti-depressants have potential concomitant and difficult side-effects in Fabry patients (e.g. accentuation of autonomic instability). Prescription of opioids carries the risk of drug dependence or abuse. Although they should only be given if other therapeutic options are ineffective, opioids may be helpful in the acute management of intolerable pain crises [96–99]. Topical application of anesthetics may provide relief of burning pain or hyperalgesia.
With increasing disability and unpredictability and difficulty of controlling the pain, patients are at risk of chronic depression . Patients should be evaluated for psychosocial and behavioral deficits and appropriately treated.
Common non-neurologic symptoms of Fabry disease and risk factors should be carefully monitored and treated as outlined in the general guidelines for the management of Fabry disease patients . Co-morbidities must be addressed and smoking discouraged as it may aggravate airflow obstruction commonly found in patients with Fabry disease , and further increase the risk of cardiovascular and cerebrovascular events. Anti-platelet drugs (aspirin, clopidogrel) are recommended for patients at risk of thrombotic events. Dyslipidemia should be treated with statins , and recently the use of statins to prevent stroke in Fabry disease has been discussed .
Enzyme replacement therapies (ERTs) are available for treatment of patients with Fabry disease and several clinical studies have reported pain outcomes [45, 73, 103–112]. For example, the Total Symptom Score improved with biweekly ERT at the dose of 1 mg/kg for 18 or 23 months , and some adults were able to discontinue their pain medication(s), or doses of pain medications could be tapered [105, 112]. Improvements in the Bodily Pain scale of the SF-36 during 2 to 3 years of treatment with ERT (1 mg/kg), particularly in younger patients, have recently been reported . Signs of recovery of small nerve fibers have been noted. Significant improvements in vibration, heat-pain, and cold perception thresholds, indicating recovery of Aβ, Aδ- and C-fiber function, have been reported in adults treated biweekly with 1 mg/kg agalsidase beta for 18 or 23 months .
As for the renal [107, 113] and cardiac complications  of Fabry disease, early initiation of treatment may provide a better outcome, i.e., improvement or more optimal preservation of peripheral nerve function. Additional studies are needed in pediatric patients to assess if early-stage treatment can prevent the often devastating peripheral neurologic burden of Fabry disease.
Small fiber dysfunction accounts for many of the incapacitating complaints reported by most children, adolescents and young adults affected by Fabry disease. These early complaints (e.g., chronic burning peripheral pain, attacks of acute excruciating peripheral pain, and manifestations of autonomic dysfunction, such as gastrointestinal dysmotility and hypohydrosis) should prompt the clinician to consider the diagnosis Fabry disease and to perform appropriate tests. The burden of the progressive neurologic disease should be assessed early, comprehensively and regularly as the neurologic disability in Fabry disease increases with age, both in males and females. Adequate management of the pain is essential for improving the quality of life of young patients, as are multidisciplinary management and timely intervention with disease specific enzyme replacement therapy.
transient ischemic attack
Pediatric Quality of Life Inventory
enzyme replacement therapy.
The 1st International Expert Panel on Neuropathy in Fabry Disease was sponsored by Genzyme Corporation. The authors wish to thank Hans Ebels, MD, of Genzyme Corporation, for his assistance in preparing this manuscript for submission. The authors maintained full and independent responsibility for the content of this manuscript.
Written informed consent was obtained from patients for publication of the clinical photographs (Figures 1 and 2). Copies of the written consents are available for review by the Editor-in-Chief of this journal.
- Hopkin RJ, Bissler J, Banikazemi M, Clarke L, Eng CM, Germain DP, Lemay R, Tylki-Szymanska A, Wilcox WR: Characterization of Fabry disease in 352 pediatric patients in the Fabry Registry. Pediatr Res. 2008, 64: 550-555. 10.1203/PDR.0b013e318183f132.PubMedGoogle Scholar
- Ramaswami U, Whybra C, Parini R, Pintos-Morell G, Mehta A, Sunder-Plassmann G, Widmer U, Beck M: Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey. Acta Paediatr. 2006, 95: 86-92.PubMedGoogle Scholar
- Zarate YA, Hopkin RJ: Fabry's disease. Lancet. 2008, 372: 1427-1435. 10.1016/S0140-6736(08)61589-5.PubMedGoogle Scholar
- Desnick R, Ioannou Y, Eng C: alpha-Galactosidase A deficiency: Fabry disease. The Metabolic and Molecular Bases of Inherited Disease. Edited by: Scriver CR, Beaudet AL, Sly WS, Valle D. 2001, New York: McGraw-Hill, 3733-3774.Google Scholar
- Fellgiebel A, Muller MJ, Ginsberg L: CNS manifestations of Fabry's disease. Lancet Neurol. 2006, 5: 791-795. 10.1016/S1474-4422(06)70548-8.PubMedGoogle Scholar
- Linhart A, Kampmann C, Zamorano JL, Sunder-Plassmann G, Beck M, Mehta A, Elliott PM: Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J. 2007, 28: 1228-1235. 10.1093/eurheartj/ehm153.PubMedGoogle Scholar
- Schiffmann R, Warnock DG, Banikazemi M, Bultas J, Linthorst GE, Packman S, Sorensen SA, Wilcox WR, Desnick RJ: Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy. Nephrol Dial Transplant. 2009, 24: 2102-2111. 10.1093/ndt/gfp031.PubMedPubMed CentralGoogle Scholar
- Sims K, Politei J, Banikazemi M, Lee P: Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events: natural history data from the Fabry Registry. Stroke. 2009, 40: 788-794. 10.1161/STROKEAHA.108.526293.PubMedGoogle Scholar
- Wanner C, Oliveira JP, Ortiz A, Mauer M, Germain DP, Linthorst GE, Serra AL, Marodi L, Mignani R, Cianciaruso B, Vujkovac B, Lemay R, Beitner-Johnson D, Waldek S, Warnock DG: Prognostic indicators of renal disease progression in adults with Fabry disease: Natural history data from the Fabry Registry. Clin J Am Soc Nephrol. 2010, 5: 2220-2228. 10.2215/CJN.04340510.PubMedPubMed CentralGoogle Scholar
- Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, Sims K, Waldek S, Pastores GM, Lee P, Eng CM, Marodi L, Stanford KE, Breunig F, Wanner C, Warnock DG, Lemay RM, Germain DP: Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab. 2008, 93: 112-128. 10.1016/j.ymgme.2007.09.013.PubMedGoogle Scholar
- Wang RY, Lelis A, Mirocha J, Wilcox WR: Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med. 2007, 9: 34-45. 10.1097/GIM.0b013e31802d8321.PubMedGoogle Scholar
- Schiffmann R, Scott LJ: Pathophysiology and assessment of neuropathic pain in Fabry disease. Acta Paediatr Suppl. 2002, 91: 48-52.PubMedGoogle Scholar
- Moller AT, Jensen TS: Neurological manifestations in Fabry's disease. Nat Clin Pract Neurol. 2007, 3: 95-106. 10.1038/ncpneuro0407.PubMedGoogle Scholar
- Low M, Nicholls K, Tubridy N, Hand P, Velakoulis D, Kiers L, Mitchell P, Becker G: Neurology of Fabry disease. Intern Med J. 2007, 37: 436-447. 10.1111/j.1445-5994.2007.01366.x.PubMedGoogle Scholar
- Aerts JM, Groener JE, Kuiper S, Donker-Koopman WE, Strijland A, Ottenhoff R, van Roomen C, Mirzaian M, Wijburg FA, Linthorst GE, Vedder AC, Rombach SM, Cox-Brinkman J, Somerharju P, Boot RG, Hollak CE, Brady RO, Poorthuis BJ: Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci USA. 2008, 105: 2812-2817. 10.1073/pnas.0712309105.PubMedPubMed CentralGoogle Scholar
- Cable WJ, Dvorak AM, Osage JE, Kolodny EH: Fabry disease: significance of ultrastructural localization of lipid inclusions in dermal nerves. Neurology. 1982, 32: 347-353.PubMedGoogle Scholar
- Cable WJ, Kolodny EH, Adams RD: Fabry disease: impaired autonomic function. Neurology. 1982, 32: 498-502.PubMedGoogle Scholar
- Fukuhara N, Suzuki M, Fujita N, Tsubaki T: Fabry's disease on the mechanism of the peripheral nerve involvement. Acta Neuropathol. 1975, 33: 9-21. 10.1007/BF00685960.PubMedGoogle Scholar
- Kocen RS, Thomas PK: Peripheral nerve involvement in Fabry's disease. Arch Neurol. 1970, 22: 81-88.PubMedGoogle Scholar
- Pellissier JF, Van Hoof F, Bourdet-Bonerandi D, Monier-Faugere MC, Toga M: Morphological and biochemical changes in muscle and peripheral nerve in Fabry's disease. Muscle Nerve. 1981, 4: 381-387. 10.1002/mus.880040506.PubMedGoogle Scholar
- Sima AA, Robertson DM: Involvement of peripheral nerve and muscle in Fabry's disease. Histologic, ultrastructural, and morphometric studies. Arch Neurol. 1978, 35: 291-301.PubMedGoogle Scholar
- Thurberg BL, Randolph Byers H, Granter SR, Phelps RG, Gordon RE, O'Callaghan M: Monitoring the 3-year efficacy of enzyme replacement therapy in fabry disease by repeated skin biopsies. J Invest Dermatol. 2004, 122: 900-908. 10.1111/j.0022-202X.2004.22425.x.PubMedGoogle Scholar
- Toyooka K, Said G: Nerve biopsy findings in hemizygous and heterozygous patients with Fabry's disease. J Neurol. 1997, 244: 464-468. 10.1007/s004150050125.PubMedGoogle Scholar
- Vital A, Vital C, Maleville J: Fabry's disease: an ultrastructural study of muscle and peripheral nerve. Clin Neuropathol. 1984, 3: 168-172.PubMedGoogle Scholar
- Wraith JE, Tylki-Szymanska A, Guffon N, Lien YH, Tsimaratos M, Vellodi A, Germain DP: Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. J Pediatr. 2008, 152: 563-570. 10.1016/j.jpeds.2007.09.007.PubMedGoogle Scholar
- Kaye EM, Kolodny EH, Logigian EL, Ullman MD: Nervous system involvement in Fabry's disease: clinicopathological and biochemical correlation. Ann Neurol. 1988, 23: 505-509. 10.1002/ana.410230513.PubMedGoogle Scholar
- Somjen GG, Herman SP, Klein R, Brubaker PE, Briner WH, Goodrich JK, Krigman MR, Haseman JK: The uptake of methyl mercury (203 Hg) in different tissues related to its neurotoxic effects. J Pharmacol Exp Ther. 1973, 187: 602-611.PubMedGoogle Scholar
- Altarescu G, Moore DF, Pursley R, Campia U, Goldstein S, Bryant M, Panza JA, Schiffmann R: Enhanced endothelium-dependent vasodilation in Fabry disease. Stroke. 2001, 32: 1559-1562.PubMedPubMed CentralGoogle Scholar
- DeGraba T, Azhar S, Dignat-George F, Brown E, Boutiere B, Altarescu G, McCarron R, Schiffmann R: Profile of endothelial and leukocyte activation in Fabry patients. Ann Neurol. 2000, 47: 229-233. 10.1002/1531-8249(200002)47:2<229::AID-ANA13>3.0.CO;2-T.PubMedGoogle Scholar
- Baron R: Mechanisms of disease: neuropathic pain--a clinical perspective. Nat Clin Pract Neurol. 2006, 2: 95-106. 10.1038/ncpneuro0113.PubMedGoogle Scholar
- Birklein F: Mechanisms of neuropathic pain and their importance in Fabry disease. Acta Paediatr Suppl. 2002, 91: 34-37.PubMedGoogle Scholar
- Desnick RJ, Brady RO: Fabry disease in childhood. J Pediatr. 2004, 144: S20-26. 10.1016/j.jpeds.2004.01.051.PubMedGoogle Scholar
- Lidove O, Ramaswami U, Jaussaud R, Barbey F, Maisonobe T, Caillaud C, Beck M, Sunder-Plassmann G, Linhart A, Mehta A: Hyperhidrosis: a new and often early symptom in Fabry disease. International experience and data from the Fabry Outcome Survey. Int J Clin Pract. 2006, 60: 1053-1059. 10.1111/j.1742-1241.2006.01061.x.PubMedGoogle Scholar
- Hilz MJ, Stemper B, Kolodny EH: Lower limb cold exposure induces pain and prolonged small fiber dysfunction in Fabry patients. Pain. 2000, 84: 361-365. 10.1016/S0304-3959(99)00236-5.PubMedGoogle Scholar
- Lacomis D, Roeske-Anderson L, Mathie L: Neuropathy and Fabry's disease. Muscle Nerve. 2005, 31: 102-107. 10.1002/mus.20130.PubMedGoogle Scholar
- Luciano CA, Russell JW, Banerjee TK, Quirk JM, Scott LJ, Dambrosia JM, Barton NW, Schiffmann R: Physiological characterization of neuropathy in Fabry's disease. Muscle Nerve. 2002, 26: 622-629. 10.1002/mus.10236.PubMedGoogle Scholar
- Hilz MJ: Evaluation of peripheral and autonomic nerve function in Fabry disease. Acta Paediatr Suppl. 2002, 91: 38-42.PubMedGoogle Scholar
- MacDermot KD, Holmes A, Miners AH: Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J Med Genet. 2001, 38: 769-775. 10.1136/jmg.38.11.769.PubMedPubMed CentralGoogle Scholar
- Torvin Møller A, Winther Bach F, Feldt-Rasmussen U, Rasmussen A, Hasholt L, Lan H, Sommer C, Kolvraa S, Ballegaard M, Staehelin Jensen T: Functional and structural nerve fiber findings in heterozygote patients with Fabry disease. Pain. 2009, 145: 237-245. 10.1016/j.pain.2009.06.032.PubMedGoogle Scholar
- Dütsch M, Marthol H, Stemper B, Brys M, Haendl T, Hilz MJ: Small fiber dysfunction predominates in Fabry neuropathy. J Clin Neurophysiol. 2002, 19: 575-586. 10.1097/00004691-200212000-00011.PubMedGoogle Scholar
- Valeriani M, Mariotti P, Le Pera D, Restuccia D, De Armas L, Maiese T, Vigevano F, Antuzzi D, Zampino G, Ricci R, Tonali P: Functional assessment of A delta and C fibers in patients with Fabry's disease. Muscle Nerve. 2004, 30: 708-713. 10.1002/mus.20174.PubMedGoogle Scholar
- Weidemann F, Strotmann JM, Breunig F, Niemann M, Maag R, Baron R, Eggert AO, Wanner C: Misleading terms in Anderson-Fabry disease. Eur J Clin Invest. 2008, 38: 191-196. 10.1111/j.1365-2362.2008.01921.x.PubMedGoogle Scholar
- Gold KF, Pastores GM, Botteman MF, Yeh JM, Sweeney S, Aliski W, Pashos CL: Quality of life of patients with Fabry disease. Qual Life Res. 2002, 11: 317-327. 10.1023/A:1015511908710.PubMedGoogle Scholar
- Street NJ, Yi MS, Bailey LA, Hopkin RJ: Comparison of health-related quality of life between heterozygous women with Fabry disease, a healthy control population, and patients with other chronic disease. Genet Med. 2006, 8: 346-353. 10.1097/01.gim.0000223545.63012.5a.PubMedGoogle Scholar
- Watt T, Burlina AP, Cazzorla C, Schonfeld D, Banikazemi M, Hopkin RJ, Martins AM, Sims K, Beitner-Johnson D, O'Brien F, Feldt-Rasmussen U: Agalsidase beta treatment is associated with improved quality of life in patients with Fabry disease: Findings from the Fabry Registry. Genet Med. 2010, 12: 703-712.PubMedGoogle Scholar
- Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ, Portenoy RK, Rice AS, Stacey BR, Treede RD, Turk DC, Wallace MS: Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007, 132: 237-251. 10.1016/j.pain.2007.08.033.PubMedGoogle Scholar
- Crosbie TW, Packman W, Packman S: Psychological aspects of patients with Fabry disease. J Inherit Metab Dis. 2009, 32: 745-753. 10.1007/s10545-009-1254-1.PubMedGoogle Scholar
- Laney DA, Gruskin DJ, Fernhoff PM, Cubells JF, Ousley OY, Hipp H, Mehta AJ: Social-adaptive and psychological functioning of patients affected by Fabry disease. J Inherit Metab Dis.
- Cole AL, Lee PJ, Hughes DA, Deegan PB, Waldek S, Lachmann RH: Depression in adults with Fabry disease: a common and under-diagnosed problem. J Inherit Metab Dis. 2007, 30: 943-951. 10.1007/s10545-007-0708-6.PubMedGoogle Scholar
- Grewal RP: Psychiatric disorders in patients with Fabry's disease. Int J Psychiatry Med. 1993, 23: 307-312. 10.2190/JKFW-3WXK-QA7N-BYLN.PubMedGoogle Scholar
- Sadek J, Shellhaas R, Camfield CS, Camfield PR, Burley J: Psychiatric findings in four female carriers of Fabry disease. Psychiatr Genet. 2004, 14: 199-201. 10.1097/00041444-200412000-00006.PubMedGoogle Scholar
- Lacomis D: Small-fiber neuropathy. Muscle Nerve. 2002, 26: 173-188. 10.1002/mus.10181.PubMedGoogle Scholar
- Tanislav C, Kaps M, Rolfs A, Bottcher T, Lackner K, Paschke E, Mascher H, Laue M, Blaes F: Frequency of Fabry disease in patients with small-fibre neuropathy of unknown aetiology: a pilot study. Eur J Neurol. 2011, 18: 631-636. 10.1111/j.1468-1331.2010.03227.x.PubMedGoogle Scholar
- Liguori R, Di Stasi V, Bugiardini E, Mignani R, Burlina A, Borsini W, Baruzzi A, Montagna P, Donadio V: Small fiber neuropathy in female patients with fabry disease. Muscle Nerve. 2010, 41: 409-412. 10.1002/mus.21606.PubMedGoogle Scholar
- Laaksonen SM, Roytta M, Jaaskelainen SK, Kantola I, Penttinen M, Falck B: Neuropathic symptoms and findings in women with Fabry disease. Clin Neurophysiol. 2008, 119: 1365-1372. 10.1016/j.clinph.2008.02.004.PubMedGoogle Scholar
- Maag R, Binder A, Maier C, Scherens A, Toelle T, Treede RD, Baron R: Detection of a characteristic painful neuropathy in Fabry disease: a pilot study. Pain Med. 2008, 9: 1217-1223. 10.1111/j.1526-4637.2008.00470.x.PubMedGoogle Scholar
- Onishi A, Dyck PJ: Loss of small peripheral sensory neurons in Fabry disease. Histologic and morphometric evaluation of cutaneous nerves, spinal ganglia, and posterior columns. Arch Neurol. 1974, 31: 120-127.PubMedGoogle Scholar
- Ro LS, Chen ST, Tang LM, Hsu WC, Chang HS, Huang CC: Current perception threshold testing in Fabry's disease. Muscle Nerve. 1999, 22: 1531-1537. 10.1002/(SICI)1097-4598(199911)22:11<1531::AID-MUS7>3.0.CO;2-O.PubMedGoogle Scholar
- Scott LJ, Griffin JW, Luciano C, Barton NW, Banerjee T, Crawford T, McArthur JC, Tournay A, Schiffmann R: Quantitative analysis of epidermal innervation in Fabry disease. Neurology. 1999, 52: 1249-1254.PubMedGoogle Scholar
- Moller AT, Feldt-Rasmussen U, Rasmussen AK, Sommer C, Hasholt L, Bach FW, Kolvraa S, Jensen TS: Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin. J Peripher Nerv Syst. 2006, 11: 119-125. 10.1111/j.1085-9489.2006.00076.x.PubMedGoogle Scholar
- Syed NA, Sandbrink F, Luciano CA, Altarescu G, Weibel T, Schiffmann R, Floeter MK: Cutaneous silent periods in patients with Fabry disease. Muscle Nerve. 2000, 23: 1179-1186. 10.1002/1097-4598(200008)23:8<1179::AID-MUS4>3.0.CO;2-7.PubMedGoogle Scholar
- Hensel H: Functional and structural basis of thermoreception. Prog Brain Res. 1976, 43: 105-118.PubMedGoogle Scholar
- Hallin RG, Torebjork HE, Wiesenfeld Z: Nociceptors and warm receptors innervated by C fibres in human skin. J Neurol Neurosurg Psychiatry. 1982, 45: 313-319. 10.1136/jnnp.45.4.313.PubMedPubMed CentralGoogle Scholar
- Kenshalo DR: Correlations of temperature sensitivity in man and monkey, a first approximation. Sensory functions of the skin in primates with special reference to man. Edited by: Zottermann Y. 1976, Oxford: Pergamon Press, 305-330.Google Scholar
- Ries M, Kim HJ, Zalewski CK, Mastroianni MA, Moore DF, Brady RO, Dambrosia JM, Schiffmann R, Brewer CC: Neuropathic and cerebrovascular correlates of hearing loss in Fabry disease. Brain. 2007, 130: 143-150.PubMedGoogle Scholar
- Morgan SH, Rudge P, Smith SJ, Bronstein AM, Kendall BE, Holly E, Young EP, Crawfurd MD, Bannister R: The neurological complications of Anderson-Fabry disease (alpha-galactosidase A deficiency)--investigation of symptomatic and presymptomatic patients. Q J Med. 1990, 75: 491-507.PubMedGoogle Scholar
- Hilz MJ: Peripheral nervous system involvement in Fabry disease: role in morbidity and mortality. Clin Ther. 2007, 29: S11-12.PubMedGoogle Scholar
- Hilz MJ, Marthol H, Schwab S, Kolodny EH, Brys M, Stemper B: Enzyme replacement therapy improves cardiovascular responses to orthostatic challenge in Fabry patients. J Hypertens. 2010, 28: 1438-1448. 10.1097/HJH.0b013e328336a077.PubMedGoogle Scholar
- Schiffmann R: Fabry disease. Pharmacol Ther. 2009, 122: 65-77. 10.1016/j.pharmthera.2009.01.003.PubMedGoogle Scholar
- Lao LM, Kumakiri M, Mima H, Kuwahara H, Ishida H, Ishiguro K, Fujita T, Ueda K: The ultrastructural characteristics of eccrine sweat glands in a Fabry disease patient with hypohidrosis. J Dermatol Sci. 1998, 18: 109-117. 10.1016/S0923-1811(98)00032-2.PubMedGoogle Scholar
- Biegstraaten M, van Schaik IN, Wieling W, Wijburg FA, Hollak CE: Autonomic neuropathy in Fabry disease: a prospective study using the Autonomic Symptom Profile and cardiovascular autonomic function tests. BMC Neurology. 2010, 10: 38-10.1186/1471-2377-10-38.PubMedPubMed CentralGoogle Scholar
- Gomes I, Nora DB, Becker J, Ehlers JA, Schwartz IV, Giugliani R, Ashton-Prolla P, Jardim L: Nerve conduction studies, electromyography and sympathetic skin response in Fabry's disease. J Neurol Sci. 2003, 214: 21-25. 10.1016/S0022-510X(03)00172-2.PubMedGoogle Scholar
- Hilz MJ, Brys M, Marthol H, Stemper B, Dutsch M: Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy. Neurology. 2004, 62: 1066-1072.PubMedGoogle Scholar
- Goldberg JM, Lindblom U: Standardised method of determining vibratory perception thresholds for diagnosis and screening in neurological investigation. J Neurol Neurosurg Psychiatry. 1979, 42: 793-803. 10.1136/jnnp.42.9.793.PubMedPubMed CentralGoogle Scholar
- Tegner R, Lindholm B: Vibratory perception threshold compared with nerve conduction velocity in the evaluation of uremic neuropathy. Acta Neurol Scand. 1985, 71: 284-289.PubMedGoogle Scholar
- Pabico RC, Atancio BC, McKenna BA, Pamukcoglu T, Yodaiken R: Renal pathologic lesions and functional alterations in a man with Fabry's disease. Am J Med. 1973, 55: 415-425. 10.1016/0002-9343(73)90140-X.PubMedGoogle Scholar
- Marchesoni CL, Roa N, Pardal AM, Neumann P, Caceres G, Martinez P, Kisinovsky I, Bianchi S, Tarabuso AL, Reisin RC: Misdiagnosis in Fabry disease. J Pediatr. 2010, 156: 828-831. 10.1016/j.jpeds.2010.02.012.PubMedGoogle Scholar
- Dyck PJ, Davies JL, Litchy WJ, O'Brien PC: Longitudinal assessment of diabetic polyneuropathy using a composite score in the Rochester Diabetic Neuropathy Study cohort. Neurology. 1997, 49: 229-239.PubMedGoogle Scholar
- Bennett MI, Attal N, Backonja MM, Baron R, Bouhassira D, Freynhagen R, Scholz J, Tolle TR, Wittchen HU, Jensen TS: Using screening tools to identify neuropathic pain. Pain. 2007, 127: 199-203. 10.1016/j.pain.2006.10.034.PubMedGoogle Scholar
- Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schutte K, Gries FA: Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia. 1995, 38: 1425-1433. 10.1007/BF00400603.PubMedGoogle Scholar
- Dworkin RH, Turk DC, Revicki DA, Harding G, Coyne KS, Peirce-Sandner S, Bhagwat D, Everton D, Burke LB, Cowan P, Farrar JT, Hertz S, Max MB, Rappaport BA, Melzack R: Development and initial validation of an expanded and revised version of the Short-form McGill Pain Questionnaire (SF-MPQ-2). Pain. 2009, 144: 35-42. 10.1016/j.pain.2009.02.007.PubMedGoogle Scholar
- Varni JW, Limbers CA: The pediatric quality of life inventory: measuring pediatric health-related quality of life from the perspective of children and their parents. Pediatr Clin North Am. 2009, 56: 843-863. 10.1016/j.pcl.2009.05.016.PubMedGoogle Scholar
- Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Neurology. 1996, 46: 1470-
- Samiy N: Ocular features of Fabry disease: diagnosis of a treatable life-threatening disorder. Surv Ophthalmol. 2008, 53: 416-423. 10.1016/j.survophthal.2008.04.005.PubMedGoogle Scholar
- Ramaswami U, Najafian B, Schieppati A, Mauer M, Bichet DG: Assessment of renal pathology and dysfunction in children with Fabry disease. Clin J Am Soc Nephrol. 2010, 5: 365-370. 10.2215/CJN.08091109.PubMedPubMed CentralGoogle Scholar
- Dyck PJ, Curtis DJ, Bushek W, Offord K: Description of "Minnesota Thermal Disks" and normal values of cutaneous thermal discrimination in man. Neurology. 1974, 24: 325-330.PubMedGoogle Scholar
- Hilz MJ, Zimmermann P, Rosl G, Scheidler W, Braun J, Stemper B, Neundorfer B: Vibrameter testing facilitates the diagnosis of uremic and alcoholic polyneuropathy. Acta Neurol Scand. 1995, 92: 486-490.PubMedGoogle Scholar
- Germain DP, Avan P, Chassaing A, Bonfils P: Patients affected with Fabry disease have an increased incidence of progressive hearing loss and sudden deafness: an investigation of twenty-two hemizygous male patients. BMC Med Genet. 2002, 3: 10-PubMedPubMed CentralGoogle Scholar
- Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, Binder A, Birbaumer N, Birklein F, Botefur IC, Braune S, Flor H, Huge V, Klug R, Landwehrmeyer GB, Magerl W, Maihofner C, Rolko C, Schaub C, Scherens A, Sprenger T, Valet M, Wasserka B: Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006, 123: 231-243. 10.1016/j.pain.2006.01.041.PubMedGoogle Scholar
- Laney DA, Fernhoff PM: Diagnosis of Fabry disease via analysis of family history. J Genet Couns. 2008, 17: 79-83. 10.1007/s10897-007-9128-x.PubMedGoogle Scholar
- Dyck PJ: Detection, characterization, and staging of polyneuropathy: assessed in diabetics. Muscle Nerve. 1988, 11: 21-32. 10.1002/mus.880110106.PubMedGoogle Scholar
- Dyck PJ, Litchy WJ, Lehman KA, Hokanson JL, Low PA, O'Brien PC: Variables influencing neuropathic endpoints: the Rochester Diabetic Neuropathy Study of Healthy Subjects. Neurology. 1995, 45: 1115-1121.PubMedGoogle Scholar
- Ries M, Mengel E, Kutschke G, Kim KS, Birklein F, Krummenauer F, Beck M: Use of gabapentin to reduce chronic neuropathic pain in Fabry disease. J Inherit Metab Dis. 2003, 26: 413-414. 10.1023/A:1025127723729.PubMedGoogle Scholar
- Politei J: Intravenous lidocaine as treatment for the painful episodes in Fabry's disease. Rev Neurol. 2009, 49: 166-167.PubMedGoogle Scholar
- Filling-Katz MR, Merrick HF, Fink JK, Miles RB, Sokol J, Barton NW: Carbamazepine in Fabry's disease: effective analgesia with dose-dependent exacerbation of autonomic dysfunction. Neurology. 1989, 39: 598-600.PubMedGoogle Scholar
- Baron R, Binder A, Wasner G: Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010, 9: 807-819. 10.1016/S1474-4422(10)70143-5.PubMedGoogle Scholar
- Cruccu G, Sommer C, Anand P, Attal N, Baron R, Garcia-Larrea L, Haanpaa M, Jensen TS, Serra J, Treede RD: EFNS guidelines on neuropathic pain assessment: revised 2009. Eur J Neurol. 2010, 17: 1010-1018. 10.1111/j.1468-1331.2010.02969.x.PubMedGoogle Scholar
- Dworkin RH, O'Connor AB, Audette J, Baron R, Gourlay GK, Haanpaa ML, Kent JL, Krane EJ, Lebel AA, Levy RM, Mackey SC, Mayer J, Miaskowski C, Raja SN, Rice AS, Schmader KE, Stacey B, Stanos S, Treede RD, Turk DC, Walco GA, Wells CD: Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clinic proceedings. 2010, 85: S3-14.PubMedPubMed CentralGoogle Scholar
- Neuropathic pain: The pharmacological management of neuropathic pain in adults in non-specialist settings (NICE clinical guideline 96). 2010, Centre for Clinical Practice at NICE, [http://guidance.nice.org.uk/CG96]
- Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ, Bultas J, Lee P, Sims K, Brodie SE, Pastores GM, Strotmann JM, Wilcox WR: Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006, 8: 539-548. 10.1097/01.gim.0000237866.70357.c6.PubMedGoogle Scholar
- Rosenberg DM, Ferrans VJ, Fulmer JD, Line BR, Barranger JA, Brady RO, Crystal RG: Chronic airflow obstruction in Fabry's disease. Am J Med. 1980, 68: 898-905. 10.1016/0002-9343(80)90224-7.PubMedGoogle Scholar
- Politei JM: Can we use statins to prevent stroke in Fabry disease?. J Inherit Metab Dis. 2009, 32: 481-487. 10.1007/s10545-009-1156-2.PubMedGoogle Scholar
- Breunig F, Weidemann F, Strotmann J, Knoll A, Wanner C: Clinical benefit of enzyme replacement therapy in Fabry disease. Kidney Int. 2006, 69: 1216-1221. 10.1038/sj.ki.5000208.PubMedGoogle Scholar
- Eng CM, Banikazemi M, Gordon RE, Goldman M, Phelps R, Kim L, Gass A, Winston J, Dikman S, Fallon JT, Brodie S, Stacy CB, Mehta D, Parsons R, Norton K, O'Callaghan M, Desnick RJ: A phase 1/2 clinical trial of enzyme replacement in fabry disease: pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet. 2001, 68: 711-722. 10.1086/318809.PubMedPubMed CentralGoogle Scholar
- Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, Caplan L, Linthorst GE, Desnick RJ: Safety and efficacy of recombinant human alpha-galactosidase A--replacement therapy in Fabry's disease. N Engl J Med. 2001, 345: 9-16. 10.1056/NEJM200107053450102.PubMedGoogle Scholar
- Eto Y, Ohashi T, Utsunomiya Y, Fujiwara M, Mizuno A, Inui K, Sakai N, Kitagawa T, Suzuki Y, Mochizuki S, Kawakami M, Hosoya T, Owada M, Sakuraba H, Saito H: Enzyme replacement therapy in Japanese Fabry disease patients: the results of a phase 2 bridging study. J Inherit Metab Dis. 2005, 28: 575-583. 10.1007/s10545-005-0575-y.PubMedGoogle Scholar
- Germain DP, Waldek S, Banikazemi M, Bushinsky DA, Charrow J, Desnick RJ, Lee P, Loew T, Vedder AC, Abichandani R, Wilcox WR, Guffon N: Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol. 2007, 18: 1547-1557. 10.1681/ASN.2006080816.PubMedGoogle Scholar
- Politei JM, Dubrovsky A: [Utility of enzyme replacement therapy in Fabry disease]. Medicina Clinica. 2010, 134: 402-405. 10.1016/j.medcli.2009.07.053.PubMedGoogle Scholar
- Schiffmann R, Floeter MK, Dambrosia JM, Gupta S, Moore DF, Sharabi Y, Khurana RK, Brady RO: Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease. Muscle Nerve. 2003, 28: 703-710. 10.1002/mus.10497.PubMedGoogle Scholar
- Schiffmann R, Kopp JB, Austin HA, Sabnis S, Moore DF, Weibel T, Balow JE, Brady RO: Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA. 2001, 285: 2743-2749. 10.1001/jama.285.21.2743.PubMedGoogle Scholar
- Vedder AC, Linthorst GE, Houge G, Groener JE, Ormel EE, Bouma BJ, Aerts JM, Hirth A, Hollak CE: Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg. PLoS ONE. 2007, 2: e598-10.1371/journal.pone.0000598.PubMedPubMed CentralGoogle Scholar
- Wilcox WR, Banikazemi M, Guffon N, Waldek S, Lee P, Linthorst GE, Desnick RJ, Germain DP: Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet. 2004, 75: 65-74. 10.1086/422366.PubMedPubMed CentralGoogle Scholar
- Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M, Finkel R, Packman S, Bichet DG, Warnock DG, Desnick RJ: Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med. 2007, 146: 77-86.PubMedGoogle Scholar
- Weidemann F, Niemann M, Breunig F, Herrmann S, Beer M, Stork S, Voelker W, Ertl G, Wanner C, Strotmann J: Long-term effects of enzyme replacement therapy on fabry cardiomyopathy: evidence for a better outcome with early treatment. Circulation. 2009, 119: 524-529. 10.1161/CIRCULATIONAHA.108.794529.PubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/11/61/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.