Late-onset fabry disease due to the p.Phe113Leu variant: the first italian cluster of five families.
Metab Brain Dis
; 38(6): 1905-1912, 2023 08.
Article
en En
| MEDLINE
| ID: mdl-37097439
ABSTRACT
BACKGROUND:
The GLA c.337T > C (p.Phe113Leu) is a known pathogenic variant associated to late-onset Fabry disease phenotype with predominant cardiac manifestations. A founder effect was demonstrated in a large cohort in the Portuguese region of Guimarães. Herein we report an in-depth phenotype description of a cluster of five Southern Italy families.METHODS:
Family pedigrees of five index males with the p.Phe113Leu variant were obtained and all at-risk relatives underwent biochemical and genetical screening test. Carriers of GLA p.Phe113Leu variant underwent subsequent multidisciplinary clinical and instrumental evaluation.RESULTS:
Thirty-one (16 M, 15 F) individuals with p.Phe113Leu pathogenic variant were identified. Sixteen out of 31 patients (51.6%) had cardiac manifestations. Notably, myocardial fibrosis was found in 7/8 patients, of whom 2 were under 40 years. Stroke occurred in 4 patients. White matter lesions were detected in 12/19 patients and occurred in 2/10 of subjects under 40 years. Seven females complained of acroparesthesias. Renal involvement occurred in 10 patients. Angiokeratomas were evident in 9 subjects. Eyes, ear, gastrointestinal and pulmonary involvement occurred in the minority of subjects.CONCLUSION:
This study demonstrates that a cluster of subjects with p.Phe113Leu pathogenic variant is also present in Southern Italy. Disease manifestations are frequent in both sexes and may occur early in life. Cardiac involvement represents the core manifestation, but neurological and renal involvement is also frequent, suggesting that extra-cardiac complications deserve clinical attention.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Fabry
/
Accidente Cerebrovascular
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Metab Brain Dis
Asunto de la revista:
CEREBRO
/
METABOLISMO
Año:
2023
Tipo del documento:
Article
País de afiliación:
Italia