Fabry Disease and Small Fiber Neuropathy
Fabry Disease and Small Fiber Neuropathy
Abstract & Commentary
By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports no financial relationships relevant to this field of study.
Synopsis: Fabry disease, while rare across the general population, is not rare as a cause of small fiber neuropathy.
Source: Tanislav C, Kaps M, Rolfs A, et al. Frequency of Fabry disease in patients with small-fibre neuropathy of unknown aetiology: A pilot study. Eur J Neurol doi:10.1111/j.1468-1331.2010.03227.x
Most often a consequence of diabetes or alcoholism in the united States, small fiber neuropathy (SFN) is a common cause of morbidity. But despite aggressive investigations, the etiology for SFN remains undiagnosed in up to 40% of patients. Fabry disease, a rare X-linked lysosomal disorder due to a-galactosidase A (a-GAL A) enzyme deficiency, may cause small fiber neuropathy early in its course. What is the prevalence of Fabry disease in this patient population?
In a retrospective study, undertaken at the Justus Liebig University Department of Neurology, Geissen, Germany, 29 patients evaluated between January 2005 and July 2009, and diagnosed with idiopathic small fiber neuropathy, were contacted and invited to undergo genetic analysis to identify the presence of an a-GAL gene mutation, which required venipuncture and urinalysis, the latter to measure protein level and globotriaosylceramide (Gb3). In selected patients, gluteal skin biopsy was performed to detect Gb3 accumulation. Inclusion criteria mandated documentation of small fiber neuropathy by quantitative testing or skin punch biopsy, normal conventional nerve conduction studies, and negative workup for common causes of small fiber neuropathy, including glucose tolerance test and glycosylated hemoglobin; liver, kidney, and thyroid function; serum protein and immunofixation electrophoresis; glycolipid and glycoprotein antibody screening; antinuclear and antineutrophil cytoplasmic antibody testing; and vitamin B12 and folate levels. Patient interviews were screened for alcoholism. Statistical analysis, due to the paucity of cases, was limited to calculation of median values and absolute range, with absolute frequencies and proportions used to analyze discrete variables.
Of 29 patients identified with idiopathic small fiber neuropathy, five either could not be reached or refused to participate, leaving 24 patients as the subjects of this study. Median age was 57.1 years (range 29.7 to 70.1 years), and 71% (n = 17) were women. Mutation of the a-GAL gene was demonstrated in five women, of which one mutation was typical and four were found to have a complex heterozygote intronic haplotype within the gene. Increased Gb3 concentrations were found in these four, but its relevance to Fabry disease pathogenesis is otherwise unclear. Fabry disease should be considered in the evaluation of patients with idiopathic painful small fiber neuropathy.
Commentary
Fabry disease is a multisystem disorder resulting from intracellular accumulation of the substrate globotriaosylceramide due to a-galactosidase A enzyme deficiency. Generally presenting in male children, symptoms may not be recognized until later in life. Symptoms most commonly include painful neuropathy (72%) and angiokeratoma (88%), but cardiac involvement, cerebrovascular disease, nephropathy ranging from proteinuria to renal failure, sensorineural hearing loss, and paroxysmal vertigo are also observed. Prior to enzyme replacement therapy and kidney transplant, death occurred in the fifth decade.
Fabry disease, while rare across the general population, is not rare as a cause of small fiber neuropathy.Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.