Fabry disease in female monozygotic twins with complex intronic haplotype variants: a case report.
Enzyme replacement therapy
Fabry disease
Introns
Monozygotic
Sequence analysis
Twins
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
07 Oct 2024
07 Oct 2024
Historique:
received:
02
06
2024
accepted:
27
09
2024
medline:
8
10
2024
pubmed:
8
10
2024
entrez:
7
10
2024
Statut:
epublish
Résumé
Fabry disease is an X-linked lysosomal storage disease caused by the impairment of α-galactosidase A. The complex intronic haplotype (CIH) variants, located in promoter and intronic regulatory lesions, has been found in patients with classical forms of Fabry disease. We present a case of Fabry disease in female monozygotic twins exhibiting the CIH mutation and classical manifestations. A 61-year-old woman with a history of stroke, carotid artery occlusion, hypertrophic cardiomyopathy, and chronic kidney disease was referred to the nephrology clinic for management of her chronic kidney disease. Her monozygotic twin sister also presented with hypertrophic cardiomyopathy, atrial flutter, carotid stenosis, and proteinuria. Clinical symptoms and a comprehensive family history strongly suggested the presence of Fabry disease. Genetic analysis revealed the presence of 5 variants within a complex intronic haplotype (CIH): c.-10 C > T, c.369 + 990 C > A, c.370 - 81_370-77delCAGCC, c.640-16 A > G, and c.1000-22 C > T. We conducted a review of the patient's previous kidney biopsy findings, which demonstrated the presence of lamellated inclusion bodies in electron microscopy. Remarkably, both the monozygotic twin sister and her son exhibited the same genetic mutation. Enzyme replacement therapy was initiated for the patient. Her kidney function decreased throughout a thorough 2-year follow-up period, while there was a slight decrease in the left ventricular mass index. This is the first reported case of female monozygotic twins with the CIH variants representing cardiac, cerebrovascular, and renal manifestations suggestive of Fabry disease.
Sections du résumé
BACKGROUND
BACKGROUND
Fabry disease is an X-linked lysosomal storage disease caused by the impairment of α-galactosidase A. The complex intronic haplotype (CIH) variants, located in promoter and intronic regulatory lesions, has been found in patients with classical forms of Fabry disease. We present a case of Fabry disease in female monozygotic twins exhibiting the CIH mutation and classical manifestations.
CASE PRESENTATION
METHODS
A 61-year-old woman with a history of stroke, carotid artery occlusion, hypertrophic cardiomyopathy, and chronic kidney disease was referred to the nephrology clinic for management of her chronic kidney disease. Her monozygotic twin sister also presented with hypertrophic cardiomyopathy, atrial flutter, carotid stenosis, and proteinuria. Clinical symptoms and a comprehensive family history strongly suggested the presence of Fabry disease. Genetic analysis revealed the presence of 5 variants within a complex intronic haplotype (CIH): c.-10 C > T, c.369 + 990 C > A, c.370 - 81_370-77delCAGCC, c.640-16 A > G, and c.1000-22 C > T. We conducted a review of the patient's previous kidney biopsy findings, which demonstrated the presence of lamellated inclusion bodies in electron microscopy. Remarkably, both the monozygotic twin sister and her son exhibited the same genetic mutation. Enzyme replacement therapy was initiated for the patient. Her kidney function decreased throughout a thorough 2-year follow-up period, while there was a slight decrease in the left ventricular mass index.
CONCLUSIONS
CONCLUSIONS
This is the first reported case of female monozygotic twins with the CIH variants representing cardiac, cerebrovascular, and renal manifestations suggestive of Fabry disease.
Identifiants
pubmed: 39375654
doi: 10.1186/s12920-024-02021-3
pii: 10.1186/s12920-024-02021-3
doi:
Substances chimiques
alpha-Galactosidase
EC 3.2.1.22
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
245Subventions
Organisme : National Research Foundation of Korea,South Korea
ID : RS-2023-00217317
Organisme : National Research Foundation of Korea,South Korea
ID : RS-2023-00217317
Organisme : Chonnam National University Hospital
ID : BCRI23046
Informations de copyright
© 2024. The Author(s).
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