FLAD1-associated multiple acyl-CoA dehydrogenase deficiency identified by newborn screening.
Mol Genet Genomic Med
; 7(9): e915, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31392824
ABSTRACT
BACKGROUND:
Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric aciduria type II, is a mitochondrial fatty acid oxidation disorder caused by variants in ETFA, ETFB, and ETFDH. Recently, riboflavin transporter genes and the mitochondrial FAD transporter gene have also been associated with MADD-like phenotype.METHODS:
We present a case of MADD identified by newborn biochemical screening in a full-term infant suggestive of both medium-chain acyl-CoA dehydrogenase deficiency and MADD. Urine organic acid GC/MS analysis was also concerning for both disorders. However, panel sequencing of ETFA, ETFB, ETFDH, and ACADM was unrevealing. Ultimately, a variant in the FAD synthase gene, FLAD1 was found explaining the clinical presentation.RESULTS:
Exome sequencing identified compound heterozygous variants in FLAD1 NM_025207.4 c.[442C>T];[1588C>T], p.[Arg148*];[Arg530Cys]. The protein damaging effects were confirmed by Western blot. The patient remained asymptomatic and there was no clinical decompensation during the first year of life. Plasma acylcarnitine and urinary organic acid analyses normalized without any treatment. Riboflavin supplementation was started at 15 months.CONCLUSION:
Newborn screening, designed to screen for specific treatable congenital metabolic diseases, may also lead to the diagnosis of additional, very rare metabolic disorders such as FLAD1 deficiency. The case further illustrates that even milder forms of FLAD1 deficiency are detectable in the asymptomatic state by newborn screening.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Deficiência Múltipla de Acil Coenzima A Desidrogenase
/
Nucleotidiltransferases
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Idioma:
En
Revista:
Mol Genet Genomic Med
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estônia