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Progressive cardiac involvement in a compound heterozygote Fabry patient: a case report.

ABSTRACT: Background:Fabry disease is an X-linked lysosomal storage disorder due to mutations in the gene encoding for alpha-galactosidase A, with subsequent accumulation of complex sphingolipids in multiple organs, including the heart. Female heterozygotes can develop cardiac involvement although this is usually milder and slower to progress compared with male hemizygotes. Case summary:A 71-year-old woman with two separate pathological Fabry mutations (N215S, C202R; compound heterozygote) presented with progressive cardiac involvement despite enzyme replacement therapy (ERT) with Replagal, as demonstrated by troponin elevation and cardiovascular magnetic resonance (CMR) findings: moderate segmental left ventricular dysfunction with wall thinning, low myocardial native T1, and extensive late gadolinium enhancement with co-located increased T2. Discussion:We report for the first time, a detailed cardiac phenotype using CMR in a compound heterozygote Fabry patient with progressive cardiac involvement despite ERT.

SUBMITTER: McConnell EJ

PROVIDER: S-EPMC6426117 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Progressive cardiac involvement in a compound heterozygote Fabry patient: a case report.

McConnell Eliza Jeanette EJ Every James J Tchan Michel M Kozor Rebecca R

European heart journal. Case reports 20181207 4

<h4>Background</h4>Fabry disease is an X-linked lysosomal storage disorder due to mutations in the gene encoding for alpha-galactosidase A, with subsequent accumulation of complex sphingolipids in multiple organs, including the heart. Female heterozygotes can develop cardiac involvement although this is usually milder and slower to progress compared with male hemizygotes.<h4>Case summary</h4>A 71-year-old woman with two separate pathological Fabry mutations (N215S, C202R; compound heterozygote) ...[more]

PMID: 31020198

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Project description:BACKGROUND: Fabry disease is an X-linked inherited metabolic condition where the deficit of the ?-galactosidase A enzyme, encoded by the GLA gene, leads to glycosphingolipid storage, mainly globotriaosylceramide. To date, more than 600 mutations have been identified in human GLA gene that are responsible for FD, including missense and nonsense mutations, small and large deletions. Such mutations are usually inherited, and cases of de novo onset occur rarely. CASE PRESENTATION: In this article we report an interesting case of a 44-year-old male patient suffering from a severe form of Fabry disease, with negative family history. The patient showed signs such as cornea verticillata, angiokeratomas, cardiac and neurological manifestations, an end-stage renal disease and he had low ?-galactosidase A activity. We detected, in this subject, the mutation c.493 G > C in the third exon of the GLA gene which causes the amino acid substitution D165H in the protein. This mutation affects the amino acid - belonging to the group of buried residues - involved, probably, in the preservation of the protein folding. Moreover, studies of multiple sequence alignment indicate that this amino acid is highly conserved, thus strengthening the hypothesis that it is a key amino acid to the enzyme functionality.The study of the relatives of the patient showed that, surprisingly, none of the members of his family of origin had this genetic alteration, suggesting a de novo mutation. Only his 11-year-old daughter - showing acroparaesthesias and heat intolerance with reduced enzymatic activity - had the same mutation. CONCLUSIONS: We suggest that a non-inherited mutation of the ?-galactosidase A gene is responsible for Fabry disease in the patient who had reduced enzyme activity and classical clinical manifestations of the disease. In a family, it is rare to find only one Fabry disease affected subject with a de novo mutation. These findings emphasize the importance of early diagnosis, genetic counselling, studying the genealogical tree of the patients and starting enzyme replacement therapy to prevent irreversible vital organ damage that occurs during the course of the disease.

Dataset Information

Progressive cardiac involvement in a compound heterozygote Fabry patient: a case report.

Publications

Progressive cardiac involvement in a compound heterozygote Fabry patient: a case report.

Similar Datasets

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