ASAH1-related disorders: Description of 15 novel pediatric patients and expansion of the clinical phenotype.
Clin Genet
; 98(6): 598-605, 2020 12.
Article
en En
| MEDLINE
| ID: mdl-32875576
ABSTRACT
Acid ceramidase deficiency is an orphan lysosomal disorder caused by ASAH1 pathogenic variants and presenting with either Farber disease or spinal muscle atrophy with progressive myoclonic epilepsy (SMA-PME). Phenotypic and genotypic features are rarely explored beyond the scope of case reports. Furthermore, the new biomarker C26-Ceramide requires validation in a clinical setting. We evaluated the clinical, biomarker and genetic spectrum of 15 Egyptian children from 14 unrelated families with biallelic pathogenic variants in ASAH1 (12 Farber and 3 SMA-PME). Recruited children were nine females/six males ranging in age at diagnosis from 13 to 118 months. We detected ASAH1 pathogenic variants in all 30 alleles including three novel variants (c.1126A>G (p.Thr376Ala), c.1205G>A (p.Arg402Gln), exon-5-deletion). Both total C26-Ceramide and its trans- isomer showed 100% sensitivity for the detection of ASAH1-related disorders in tested patients. A 10-year-old girl with the novel variant c.1205G>A (p.Arg402Gln) presented with a new peculiar phenotype of PME without muscle atrophy. We expanded the phenotypic spectrum of ASAH1-related disorders and validated the biomarker C26-Ceramide for supporting diagnosis in symptomatic patients.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Epilepsias Mioclónicas Progresivas
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Miopatías Distales
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Lipogranulomatosis de Farber
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Ceramidasa Ácida
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Mioclonía
Límite:
Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Clin Genet
Año:
2020
Tipo del documento:
Article
País de afiliación:
Egipto