Fabry Disease Flashcards
A 30-year-old man presents to the clinic with complaints of chronic burning pain in his hands and feet that worsens with exercise or heat. He reports episodes of dark-colored urine and has a family history of early cardiac deaths in male relatives. On examination, there are scattered angiokeratomas on his trunk and lower abdomen. Laboratory testing reveals proteinuria, elevated serum creatinine, and decreased α-galactosidase A activity. Which of the following is the most appropriate next step in management?
A) Dietary protein restriction
B) Enzyme replacement therapy
C) Antiplatelet therapy with aspirin
D) Regular phlebotomy
E) Initiation of corticosteroids
Answer: B) Enzyme replacement therapy
Explanation: Fabry Disease is an X-linked lysosomal storage disorder caused by a deficiency in α-galactosidase A, leading to the accumulation of globotriaosylceramide (Gb3) in multiple tissues. Clinical manifestations include neuropathic pain (acroparesthesia), angiokeratomas, hypohidrosis, and renal involvement (proteinuria and progressive kidney failure). Late complications include left ventricular hypertrophy, arrhythmias, and cerebrovascular disease. The primary treatment is enzyme replacement therapy (e.g., recombinant α-galactosidase A), which helps reduce substrate accumulation and slows disease progression.
Incorrect Answers:
A) Dietary protein restriction is used in certain renal diseases, but it does not address the underlying lysosomal enzyme deficiency in Fabry disease.
C) Antiplatelet therapy with aspirin is not indicated unless there is a concurrent vascular or thrombotic condition (e.g., stroke or myocardial infarction).
D) Regular phlebotomy is the treatment for hemochromatosis, a disorder of iron metabolism, and has no role in Fabry disease.
E) Corticosteroids are used in autoimmune or inflammatory conditions but are not effective for lysosomal storage disorders like Fabry disease.
What is the genetic inheritance pattern of Fabry Disease?
X-linked recessive inheritance
What enzyme deficiency causes Fabry Disease?
Deficiency of α-galactosidase A
What is the primary substrate that accumulates in Fabry Disease?
Accumulation of globotriaosylceramide (Gb3)
What are the common early clinical manifestations of Fabry Disease?
Neuropathic pain (acroparesthesia), angiokeratomas, hypohidrosis, corneal verticillata
What cardiac manifestations are seen in Fabry Disease?
Left ventricular hypertrophy, arrhythmias, and cardiomyopathy
What are the late complications of Fabry Disease?
Renal failure, left ventricular hypertrophy, arrhythmias.
increased risk for thrombosis –> stroke
How is Fabry Disease diagnosed?
Reduced α-galactosidase A activity in leukocytes; genetic testing
What is the primary treatment for Fabry Disease?
Enzyme replacement therapy (e.g., recombinant α-galactosidase A)
What medications are used for managing neuropathic pain in Fabry Disease?
Neuropathic pain is treated with gabapentin or carbamazepine
What renal complication is associated with Fabry Disease?
Proteinuria and progressive kidney failure
What is the prognosis of Fabry Disease?
patients can live into adulthood.
