Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients.
Genes (Basel)
; 12(9)2021 08 27.
Article
en En
| MEDLINE
| ID: mdl-34573316
ABSTRACT
The variants of electron transfer flavoprotein (ETFA, ETFB) and ETF dehydrogenase (ETFDH) are the leading cause of glutaric aciduria type II (GA-II). In this study, we identified 13 patients harboring six variants of two genes associated with GA-II. Out of the six variants, four were missense, and two were frameshift mutations. A missense variant (ETFDHp.Gln269His) was observed in a homozygous state in nine patients. Among nine patients, three had experienced metabolic crises with recurrent vomiting, abdominal pain, and nausea. In one patient with persistent metabolic acidosis, hypoglycemia, and a high anion gap, the ETFDHp.Gly472Arg, and ETFBp.Pro94Thrfs*8 variants were identified in a homozygous, and heterozygous state, respectively. A missense variant ETFDHp.Ser442Leu was detected in a homozygous state in one patient with metabolic acidosis, hypoglycemia, hyperammonemia and liver dysfunction. The ETFDHp.Arg41Leu, and ETFBp.Ile346Phefs*19 variants were observed in a homozygous state in one patient each. Both these variants have not been reported so far. In silico approaches were used to evaluate the pathogenicity and structural changes linked with these six variants. Overall, the results indicate the importance of a newborn screening program and genetic investigations for patients with GA-II. Moreover, careful interpretation and correlation of variants of uncertain significance with clinical and biochemical findings are needed to confirm the pathogenicity of such variants.
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Bases de datos:
MEDLINE
Asunto principal:
Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Genes (Basel)
Año:
2021
Tipo del documento:
Article
País de afiliación:
Emiratos Árabes Unidos