Forskning ved Københavns Universitet - Københavns Universitet


Diagnostic dilemma: a young woman with Fabry disease symptoms, no family history, and a "sequencing cryptic" α-galactosidase a large deletion

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Feldt-Rasmussen, Ulla
  • Robert Dobrovolny
  • Irina Nazarenko
  • Martin Ballegaard
  • Lis Frydenreich Hasholt
  • Ase K Rasmussen
  • Erik I Christensen
  • Soren S Sorensen
  • Flemming Wibrand
  • Robert J Desnick
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.
TidsskriftMolecular Genetics and Metabolism
Udgave nummer3
Sider (fra-til)314-8
Antal sider5
StatusUdgivet - 2011

ID: 40146939