Screening and follow-up results of neonate medium-chain acyl-CoA dehydrogenase deficiency in Zibo, Shandong province.

Objective: To analyze the incidence, phenotype, genotype and prognosis of neonatal medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in Zibo city of Shandong province.
Methods: A total of 241 297 neonates were screened for MCADD in Zibo city of Shandong province from November 2013 to January 2022. Non-derivatized tandem mass spectrometry was used to detect blood free carnitine and acylcarnitine profiles in neonatal screening. Neonates with octanoylcarnitine (C8)≥0.25 μmol/L, or combined with C8/decanoylcarnitine (C10)≥1.5 were recalled, and second-generation high-throughput sequencing was performed for genetic diagnosis.
Results: Among 241 297 neonates, 6 cases of MCADD were screened, including 2 boys and 4 girls, with an incidence of 1/40 216. Two mutation sites of ACADM gene were identified in all MCADD infants, and 12 mutation with 8 types were detected in total. The hot spot mutations were c.449_452del (p.T150Rfs*4) and c.387+1delG， and exon 11 c.1076C>T (p.A359V) was a newly detected mutation. No phenotype-genotype correlation was found. One case died on day 4 after birth; 5 cases were followed up for 2 to 60 months, none of them received special diet treatment. The growth and intellectual development of the surviving cases were normal, and no abnormality was found in routine biochemical indicators.
Conclusions: The incidence of MCADD in Zibo city seems to be higher than that in other areas in China. The ACADM gene mutations c.449_452del (p.T150Rfs*4) and c.387+1delG are common, and a new mutation c.1076C>T (p.A359V) has been detected. No phenotype-genotype correlation has been found. Early diagonsis and treatment are effective measures to reduce poor prognosis.