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Chapter 47: Fabry Disease

A 20-year-old man presents with a history of pain in his extremities. He was referenced by his family physician as his routine urinalysis revealed only isosthenuria and microalbuminuria.

Which ONE of the following is the MOST LIKELY diagnosis?

A. Juvenile rheumatoid arthritis

B. Fabry disease

C. Alport syndrome

D. Glomerulonephritis

E. Nephrotic syndrome

The answer is B. Only answer Fabry disease accounts for the acroparesthesias (pain in the hands and feet) and urinalysis findings, as the other diseases would have had marked proteinuria.

Fabry disease is an X-linked disorder in which male patients are affected and female heterozygotes can be asymptomatic or have manifestations as severe as their affected male relatives.

Which ONE is the MOST accurate method to diagnose heterozygous females?

A. α-Galactosidase A activity in leukocytes

B. Identification of the family mutation

C. Slit lamp microscopy to identify the characteristic corneal opacity

D. Measurement of the urinary glycosphingolipid accumulation

E. Kidney biopsy revealing lysosomal glycolipid inclusions

The answer is B. Identification of the family mutation is the best and most accurate method to diagnose Fabry disease in symptomatic and asymptomatic female heterozygotes. In female heterozygotes, the leukocyte enzyme level can be normal; and only a percentage (80–90%) of DNA-confirmed heterozygotes have the keratopathy. Urinary Gb3 levels may vary in heterozygotes from essentially normal to markedly elevated. Although the kidney biopsy would be diagnostic, it is particularly invasive.

Screening males in your dialysis clinic for Fabry disease by a simple enzyme assay identifies two males with marked α-galactosidase A deficiency suggesting the diagnosis of Fabry disease, a rare treatable lysosomal storage disease which progresses to renal failure.

Which ONE of the following is the MOST effective treatment for this disease?

A. Renal transplantation, as the normal kidney will not only correct the renal disease, but will secrete the normal enzyme.

B. Continue the dialysis, as the toxic circulating substrate (~1000 molecular weight) will be cleared.

C. Recombinant enzyme replacement therapy.

D. The patient has lost his kidney function, continue dialysis or consider transplantation, and screen family members to identify at-risk young males for evaluation and treatment.

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