A late-onset male Fabry disease patient with somatic mosaicism of a classical GLA mutation: a case report
| Autor: | Seong Kwon Ma, Soo Wan Kim, Chang Seok Ki, Eun Hui Bae, Han-Wook Yoo, Jong Moon Choi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Somatic cell Buccal swab 030105 genetics & heredity medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Humans Allele Advanced and Specialized Nursing Creatinine Mutation Mosaicism business.industry Enzyme replacement therapy medicine.disease Fabry disease Galactosidases 030104 developmental biology Anesthesiology and Pain Medicine Endocrinology chemistry Albuminuria Fabry Disease medicine.symptom business |
| Zdroj: | Annals of Palliative Medicine. 10:4926-4931 |
| ISSN: | 2224-5839 2224-5820 |
| DOI: | 10.21037/apm-19-635 |
| Popis: | Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA). Male patients of FD develop early sign and symptoms in childhood or adolescence. However, "de novo somatic mosaicism" is rare and might be developed a relatively mild phenotype despite carrying a classic type. A 34-year-old male patient visited with foamy urine. Renal biopsy findings were consistent with FD. Leukocyte α-galactosidase activity was markedly reduced at 5.3 nmol/hr/mg (normal range, 25-126). Sequence analysis of the patient's GLA gene identified mosaicism for the mutation GLA[NM_000169.2] c.820=/G>C. This mutation results in a substitution of the amino acid in position 274 from glycine to arginine. However, no family members showed FD-related symptoms, and the daughter of the patient was also tested for paternity and was identified as a real biological daughter, but DNA sequence analysis for FD showed no mutations. Based on these results, we diagnosed the patients as de novo mutation with somatic mosaicism. Next generation sequencing turned out that 58% of the readings had the mutated allele in buccal cells, 84% in blood, and 85% in urine, when 100% should be expected in a hemizygous affected male confirming the presence of somatic mosaicisms. The patient has been on treatment for enzyme replacement therapy (agalsidase-β, 1.0 mg/kg biweekly) for past 9 years and has maintained normal renal function (serum creatinine 1.0 mg/dL) with mild albuminuria (123 mg/g Cr). Therefore, this case suggests somatic mosaicism is one of important phenotype modifiers. |
| Databáze: | OpenAIRE |
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