Variants of unknown significance: Adding trauma to trauma. A case study of sudden unexplained death in a child

Abstract

cess. Suspicion for Fabry disease was raised after recognising his periumbilical rash was angiokeratoma. Diagnosis was confirmed with an almost undetectable leucocyte a-galactosidase level. Subsequent genotyping demonstrated hemizygosity for p.L334Pmutation. The patientwas commenced on twoweekly enzyme replacement therapy and had no further heart failure decompensation. Case 2: A 63 year-old man was referred for cardiac transplant assessment with “burnt-out” familial hypertrophic cardiomyopathy. Symptoms included tinnitus, limited sweating and temperature intolerance. Leucocyte a-galactosidase deficiency led to a revised diagnosis of Fabry disease. The patient’s heart failure deteriorated despite enzyme replacement and he underwent orthotopic cardiac transplant 12 months later. He continues to receive regular enzyme replacement and has normal allograft function and histology 14 months post transplant. Affected family members were identified and referred. Our cases highlight that Fabry disease should be considered in the differential diagnosis of older males with heart failure and left ventricular hypertrophy. Early diagnosis and treatment with enzyme replacement could halt disease progression in the index subjects and their affected family.