Diagnostic dilemma: a young woman with Fabry disease symptoms, no family history, and a "sequencing cryptic" a-galactosidase a large deletion
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Fabry disease, an X-linked lysosomal storage disorder, results from the deficient activity of a-galactosidase A (a-Gal A). In affected males, the clinical diagnosis is confirmed by the markedly decreased a-Gal A activity. However, in female heterozygotes, the a-Gal A activity can range from low to normal due to random X-chromosomal inactivation, and diagnostic confirmation requires identification of the family's a-Gal A gene mutation. In a young female who had occasional acroparesthesias, corneal opacities, and 15 to 50% of the lower limit of normal leukocyte a-Gal A activity, a-Gal A sequencing in two expert laboratories did not identify a confirmatory mutation, presenting a diagnostic dilemma. A renal biopsy proved diagnostic and renewed efforts to detect an a-Gal A mutation. Subsequent gene dosage analyses identified a large a-Gal A deletion confirming her heterozygosity, and she was started on enzyme replacement therapy. Thus, gene dosage analyses can detect large deletions (>50bp) in suspect heterozygotes for X-linked and autosomal dominant diseases that are "sequencing cryptic," resolving molecular diagnostic dilemmas.
Originalsprog | Engelsk |
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Tidsskrift | Molecular Genetics and Metabolism |
Vol/bind | 104 |
Udgave nummer | 3 |
Sider (fra-til) | 314-8 |
Antal sider | 5 |
ISSN | 1096-7192 |
DOI | |
Status | Udgivet - 2011 |
ID: 38489246