Neuropathy and Fabry's disease

Lacomis, David; Roeske-Anderson, Lisa; Mathie, Laurie

doi:10.1002/mus.20130

Cited by 29 publications

(18 citation statements)

References 27 publications

(45 reference statements)

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“…In childhood, other possible causes of pain such as rheumatoid arthritis [286], rheumatic fever, systemic lupus erythematosus, Raynaud's disease, and 'growing pains' (a frequent misdiagnosis in children with FD) must be ruled out. In adulthood, celiac disease and multiple sclerosis [287] are the most often-cited differential diagnoses particularly in females.…”

Section: Reviewmentioning

confidence: 99%

Fabry disease

Germain

2010

Orphanet J Rare Dis

1,048

1,230

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Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, whereas dialysis or renal transplantation are available for patients experiencing end-stage renal failure. With age, progressive damage to vital organ systems develops and at some point, organs may start to fail in functioning. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated males and females with reductions of 20 and 10 years, respectively, as compared to the general population. While there is increasing evidence that long-term enzyme therapy can halt disease progression, the importance of adjunctive therapies should be emphasized and the possibility of developing an oral therapy drives research forward into active site specific chaperones.

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Section: Reviewmentioning

confidence: 99%

Fabry disease

Germain

2010

Orphanet J Rare Dis

1,048

1,230

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“…In addition, it is possible that some aspects of gastrointestinal symptomatology in Fabry disease may relate to as yet unidentified and subtle immunological alterations relating to lymphocytes and Gramnegative bacteria [12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Ileocecal Appendix Involvement in Fabry Disease Mimicking an Acute Abdomen

Cristi¹,

Massari²

2014

J Gastrointest Dig Syst

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Anderson-Fabry disease (AFD) is a rare, X-linked, lysosomal storage disorder due to a deficiency of alphagalactosidase A. The direct consequence is a lipid storage with the accumulation of glycosphingolipids throughout the body.The clinical picture is highly variable and depends on cellular storage deposition ranging from neurological, cutaneous and renal symptoms to cardiac and gastrointestinal ones.We are reporting about the case of a young female carrier of alpha-galactosidase A (agalA) gene mutation who was treated at our out-clinic practice for minimal neurological involvement (achroparaestesia). She was subsequently admitted in order to undergo appendectomy because of an acute severe abdominal pain. The histological examination of her appendix revealed only a deposition of globotriaosylceramide (Gb3) without any sign of acute inflammation.This case confirms the extreme clinical variability of Fabry disease and how the gastrointestinal involvement diagnosis can be missed.

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“…31 Neurologic examination is normal, as well as electromyography (EMG) and electroneurography. 32 Both examinations only assess large nerve fibers function, while in AFD small nerve fibers are involved, and their reduced density on skin biopsy is sometimes required to diagnose AFD neuropathy. 33 The neuropathic pain is difficult to manage with standard analgesic and may respond to narcotic analgesic (such as codeine or morphine) or anticonvulsant drugs (such as carbamazepine).…”

Section: Anderson-fabry Disease In the Childhood: First Signs And Symmentioning

confidence: 99%

Anderson-Fabry, the Histrionic Disease: From Genetics to Clinical Management

Cecchi¹,

Tomberli

Morrone

2013

Cardiogenetics

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Anderson-Fabry disease (AFD) is an Xlinked lysosomal storage disorder of glycosphingolipid catabolism, due to deficiency or absence of a galactosidase A (α-gal A) enzyme. The disease may affect males and females, the latter with an average 10 years delay. Metabolites storage (mostly Gb3 and lyso-Gb3) leads to progressive cellular and multiorgan dysfunction, with either early and late onset variable clinical manifestations that usually reduce quality of life and life expectancy. Heart and kidney failure, stroke and sudden death are the most devastating complications. AFD is always been considered a very rare disease, although new epidemiologic data, based on newborn screening, showed that AFD prevalence is probably underestimated and much higher than previously reported, especially for late-onset atypical phenotypes. Currently, the diagnosis may be easier and simpler by evaluating α-gal A enzyme activity and genetic analysis for GLA gene mutations on dried blood spot. While a marked α-gal A deficiency leads to diagnosis of AFD in hemizygous males, the molecular analysis is mandatory in heterozygous females. However, referral to a center with an expert multidisciplinary team is highly advisable, in order to ensure careful management and treatment of patients, based also on accurate molecular and biochemical data interpretation. While long-term efficacy of enzyme replacement therapy (ERT) in advanced stage is still debated, increasing evidence shows greater efficacy of early treatment initiation. Concomitant, organ-specific therapy is also needed. New treatment approaches, such as chemical chaperone therapy, alone or in combination with ERT, are currently under investigation. The present review illustrates the major features of the disease, focusing also on biochemical and genetic aspects

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Neuropathy and Fabry's disease

Cited by 29 publications

References 27 publications

Fabry disease

Fabry disease

Ileocecal Appendix Involvement in Fabry Disease Mimicking an Acute Abdomen

Anderson-Fabry, the Histrionic Disease: From Genetics to Clinical Management

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