Fabry's disease overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ghazal Sanadgol, M.D.[2]
Overview
Fabry's disease (also known as alpha-galactosidase A deficiency, ceramide trihexosidase deficiency, angiokeratoma corporis diffusum, Anderson Fabry disease) is an X-linked recessive inherited lysosomal storage disorder.
Historical Perspective
Fabry's disease is a rare inherited genetic condition that leads to the α-galactosidase A enzyme deficiency in individuals. Fabry's disease (or Anderson - Fabry disease) was first described separately by two physicians at the end of the 19th century. The feature and pathophysiology of the disease have been revealed through the years by various scientists.
Classification
Fabry's disease can be classified based on its different phenotypes or complications. Its different phenotypes are: classic and late-onset. The different complications involves: cardiac, renal, and neuropathic forms.
Pathophysiology
Genes involved in the pathogenesis of Fabry's disease include the GLA gene, which codes the important enzyme of alpha-galactosidase. The absence or lack of this enzyme causes Gb3 accumulation in different organs. The main pathological finding is detection of these inclusion in different cells with electron microscopies.
Causes
Fabry's disease is caused by a mutation in the GLA gene.
Differentiating Fabry's disease from Other Diseases
Fabry's disease is often misdiagnosed due to its rarity and wide range of non-specific clinical manifestations. Fabry's disease be differentiated from various kind of condition based on the symptoms and organ involvement.
Epidemiology and Demographics
Fabry's disease is a rare condition with a prevalence of approximately 6:100,000 to 0.8:100,000 in men. This disease mostly affects men and has no rational disparities.
Risk Factors
There are no established risk factors for Fabry's disease.
Screening
According to National society of Genetic Counselors, screening for Fabry's disease in patient family member is recommended. The early prenatal and newborn screening can be done by α-Gal A enzyme and GLA mutation analyses. Based on American Heart Failure society the Fabry's disease screening should be done in males with unexplained cardiac hypertrophy.
Natural History, Complications, and Prognosis
If Fabry's disease leaves untreated it can lead to end-stage renal disease (ESRD), cardiomyopathy, and stroke which are the main causes of death in these patients. Enzyme replacement therapy (ERT) treatment has an important role in their life expectancy and disease complications.
Diagnosis
History and Symptoms
A positive history of angiokeratomas, peripheral neuropathies, gradually decreased sweating, and gastrointestinal manifestations in childhood are suggestive of classic Fabry's disease. In the late-onset form of the disease neuropathic pain and gastrointestinal manifestation is not common and they may have organ-specific symptoms.
Physical Examination
The presence of angiokeratomas on physical examination is highly suggestive of Fabry's disease. other physical examinations can be varied due to organ involvement.
Laboratory Findings
A reduced concentration of serum Alpha-galactosidase A level or its activity is diagnostic of Fabry's disease. Other laboratory findings can vary due to organ involvement.
Electrocardiogram
However the ECG patterns are not specific for Fabry's , it may be helpful in the diagnosis of Fabry's disease cardiac complications.
CT scan
CT scan can show different non-specific aspects of the brain, lung, and kidney involvement in Fabry's disease.
MRI
MRI can play an important role in the diagnosis of the brain and cardiac complications of Fabry's disease. there are also some non-specific findings in renal involvement.
Echocardiography and ultrasound
Echocardiography and renal ultrasound can reveal the diagnostic pattern of Fabry's disease in these particular organs.
Other Imaging Findings
There are no other imaging findings associated with Fabry's disease.
Other Diagnostic Studies
There are no other diagnostic studies associated with Fabry's disease.
Treatment
Medical Therapy
The mainstay of therapy for Fabry's disease is enzyme replacement by Agalsidases. Other treatment is increasing the enzyme activity by Migalastat. There are also some general treatments for Fabry's disease complications.
Surgery
Kidney transplantation can be a surgical option in certain Fabry's disease patients.