Abstract
Fabry disease (FD) is an inborn error of metabolism characterized by deficient/absent activity of lysosomal enzyme alpha-galactosidase A, which results in systemic accumulation of glycosphingolipids and progression to renal failure, heart and cerebrovascular disease, and small-fiber peripheral neuropathy. This article describes a Brazilian family affected by FD caused by a novel mutation in exon 6 of the alpha-galactosidase A (GLA) gene (c.812G>C). Signs and symptoms identified were pain crisis, acroparesthesia, hypohidrosis, abdominal cramps and diarrhea, chronic kidney disease, cornea verticillata, left ventricular hypertrophy, and complete heart block. Headache was a common complaint and 1 of the patients presented with aseptic meningitis. The novel missense mutation in the GLA gene identified in this Brazilian family is consistent with the classic FD phenotype.
Highlights
Fabry disease (FD; Online Mendelian Inheritance in Man [OMIM]301500) is an inborn error of glycosphingolipid catabolism characterized by deficient/absent activity of lysosomal enzyme alpha-galactosidase A (GLA).[1,2,3] The result of impaired enzyme activity is accumulation of glycosphingolipids, mainly globotriaoslyceramide (Gb3), in plasma and cellular lysosomes.[2,3] To date, more than 600 mutations responsible for FD have been identified.[4]
Accumulation of Gb3 leads to renal failure, heart and cerebrovascular disease, and small-fiber peripheral neuropathy among other signs and symptoms.[2]
Mutations in the GLA gene responsible for FD are located in Xq22
Summary
Fabry disease (FD; Online Mendelian Inheritance in Man [OMIM]301500) is an inborn error of glycosphingolipid catabolism characterized by deficient/absent activity of lysosomal enzyme alpha-galactosidase A (GLA).[1,2,3] The result of impaired enzyme activity is accumulation of glycosphingolipids, mainly globotriaoslyceramide (Gb3), in plasma and cellular lysosomes.[2,3] To date, more than 600 mutations responsible for FD have been identified.[4]. The index patient is a 15-year-old boy (III-5) who presented with relapsing bouts of pain on hands and feet and fever as high as 39.5C. Patient II-3 had a 19-year history of bouts of pain and edema on hands and feet and repeated hospital admissions. The ERT continued and the patient still complained of worsening symptoms of limb pain alongside elevated lyso-Gb3 values. Anticonvulsant medication was changed to lamotrigine 100 mg/d, and during hospital admission the patient received intravenous lidocaine 2% for 5 days with adequate control of pain. Member Sex Age, y (ref: ≥ 2.5 mmol/L/h) GLA gene mutation (ref: 1.3 + 0.9 ng/mL) Symptoms. Acroparesthesia, hypohidrosis, heat intolerance, abdominal cramps and diarrhea, migraine, aseptic meningitis, cornea verticillata, myocardial hypertrophy, elevated CRP. III-5 Pain crises with fever, acroparesthesia, heat intolerance, hypohidrosis, cornea verticillata
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