NDLI: Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency

Content Provider	Springer Nature : BioMed Central
Author	Couce, Maria Luz Sánchez-Pintos, Paula Diogo, Luisa Leão-Teles, Elisa Martins, Esmeralda Santos, Helena Bueno, Maria Amor Delgado-Pecellín, Carmen Castiñeiras, Daisy E Cocho, José A García-Villoria, Judit Ribes, Antonia Fraga, José M Rocha, Hugo
Abstract	Background Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited defect in the mitochondrial fatty acid oxidation pathway, resulting in significant morbidity and mortality in undiagnosed patients. Newborn screening (NBS) has considerably improved MCADD outcome, but the risk of complication remains in some patients. The aim of this study was to evaluate the relationship between genotype, biochemical parameters and clinical data at diagnosis and during follow-up, in order to optimize monitoring of these patients. Methods We carried out a multicenter study in southwest Europe, of MCADD patients detected by NBS. Evaluated NBS data included free carnitine (C0) and the acylcarnitines C8, C10, C10:1 together with C8/C2 and C8/C10 ratios, clinical presentation parameters and genotype, in 45 patients. Follow-up data included C0 levels, duration of carnitine supplementation and occurrence of metabolic crises. Results C8/C2 ratio and C8 were the most accurate biomarkers of MCADD in NBS. We found a high number of patients homozygous for the prevalent c.985A > G mutation (75%). Moreover, in these patients C8, C8/C10 and C8/C2 were higher than in patients with other genotypes, while median value of C0 was significantly lower (23 μmol/L vs 36 μmol/L). The average follow-up period was 43 months. To keep carnitine levels within the normal range, carnitine supplementation was required in 82% of patients, and for a longer period in patients homozygotes for the c.985A>G mutation than in patients with other genotypes (average 31 vs 18 months). Even with treatment, median C0 levels remained lower in homozygous patients than in those with other genotypes (14 μmol/L vs 22 μmol/L). Two patients died and another three suffered a metabolic crisis, all of whom were homozygous for the c.985 A>G mutation. Conclusions Our data show a direct association between homozygosity for c.985A>G and lower carnitine values at diagnosis, and a higher dose of carnitine supplementation for maintenance within the normal range. This study contributes to a better understanding of the relationship between genotype and phenotype in newborn patients with MCADD detected through screening which could be useful in improving follow-up strategies and clinical outcome.
Related Links	https://ojrd.biomedcentral.com/counter/pdf/10.1186/1750-1172-8-102.pdf
Ending Page	6
Page Count	6
Starting Page	1
File Format	HTM / HTML
ISSN	17501172
DOI	10.1186/1750-1172-8-102
Journal	Orphanet Journal of Rare Diseases
Issue Number	1
Volume Number	8
Language	English
Publisher	BioMed Central
Publisher Date	2013-07-10
Access Restriction	Open
Subject Keyword	Medicine Public Health Pharmacology Toxicology Human Genetics L-carnitine Metabolic decompensation Mitochondrial fatty acid oxidation Mutations Newborn screening Rare disease Medicine/Public Health Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Pharmacology (medical) Genetics (clinical)
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.9/2023

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