FLAD1-associated multiple acyl-CoA dehydrogenase deficiency identified by newborn screening

Molecular Genetics & Genomic Medicine
Kai MuruKatrin Õunap

Abstract

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. 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. 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. Newborn screening, designed to screen for specific treatable congenita...Continue Reading

References

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Oct 5, 2011·Biochimica Et Biophysica Acta·Tânia G LucasCláudio M Gomes
Apr 8, 2015·American Journal of Medical Genetics. Part a·Sander PajusaluKatrin Õunap
Mar 5, 2016·The New England Journal of Medicine·Manuel SchiffCécile Acquaviva-Bourdain
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Aug 1, 2018·Neuromuscular Disorders : NMD·Yılmaz YıldızAyşegül Tokatlı
Nov 15, 2018·Clinical Genetics·Judit García-VilloriaAntonia Ribes

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Citations

Jun 3, 2020·International Journal of Molecular Sciences·Signe MosegaardRikke Katrine Jentoft Olsen
Dec 7, 2020·The International Journal of Biochemistry & Cell Biology·Michelle MereisFrancois H van der Westhuizen

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Methods Mentioned

BETA
Protein assay

Software Mentioned

Genome Analysis Toolkit
MassHunter

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