AUTHOR=Zhou Wei , Li Huizhong , Wang Chuanxia , Wang Xiuli , Gu Maosheng 

TITLE=Newborn Screening for Methylmalonic Acidemia in a Chinese Population: Molecular Genetic Confirmation and Genotype Phenotype Correlations

JOURNAL=Frontiers in Genetics

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00726

DOI=10.3389/fgene.2018.00726

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Methylmalonic acidemia (MMA) incidence was evaluated based on newborn screening in Xuzhou from November 2015 to December 2017, and the clinical, biochemical and molecular characteristics of patients with MMA harboring <italic>MMACHC</italic> and <italic>MUT</italic> mutations were summarized.</p><p><bold>Methods:</bold> During the study, 236,368 newborns were screened for MMA by tandem mass spectrometry (MS/MS) in the Maternity and Child Health Care Hospital of Xuzhou. C3, C3/C2 and methionine, and tHcy if necessary, were measured during the first screening. Blood samples from the infants and/or their family members were used for DNA analysis. The entire coding regions of the <italic>MMACHC</italic> and <italic>MUT</italic> genes associated with MMA were sequenced by DNA MassARRAY and next-generation sequencing (NGS).</p><p><bold>Results:</bold> Eleven patients with <italic>MMACHC</italic> mutations and three with <italic>MUT</italic> mutations were identified among the 236,368 screened newborns; the estimated total incidence of MMA was 1:16,883. Among the MMA patients, two died of infection-triggered metabolic crisis approximately 3 months after birth. All the patients identified had two mutant alleles except for one individual with early-onset disease. The most common <italic>MMACHC</italic> mutation was c.609G &gt; A. The laboratory levels of C3 and C3/C2 were elevated in MMA individuals compared to other infants. Importantly, we demonstrate that accelerated C2 degradation is related to air temperature and humidity.</p><p><bold>Conclusion:</bold> Our study reports the clinical characteristics of MMA and diagnosis through MS/MS and NGS. There was a higher incidence of MMA with homocysteinemia than of isolated MMA in Xuzhou. Insight from this study may help explain the high false-positive rate of MMA in summer.</p>