Original Research ARTICLE
Newborn screening for methylmalonic acidemia in a Chinese population. Molecular genetic confirmation and genotype phenotype correlations.
- 1Xuzhou Maternity and Child Health Care Hospital, China
Background: Methylmalonic acidemia (MMA) incidence was evaluated based on newborn screening in Xuzhou from November 2015 to December 2017, the clinical, biochemical and molecular characteristics of patients with MMA harboring MMACHC and MUT mutations were summarized.
Methods: 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 MMACHC and MUT genes associated with MMA were sequenced by DNA MassARRAY and next-generation sequencing (NGS).
Results: Eleven patients with MMACHC mutations and three with MUT 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 MMACHC mutation was c.609G>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.
Conclusion: 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.
Keywords: Methylmalonic acidemia, Newborn screening, MMACHC, Mut, MS/MS (tandem mass spectrometry)
Received: 19 Jul 2018;
Accepted: 22 Dec 2018.
Edited by:Enrico Baruffini, University of Parma, Italy
Reviewed by:Edward Quadros, SUNY Downstate Medical Center, United States
Irini Manoli, National Institutes of Health (NIH), United States
Copyright: © 2018 Zhou, Li, Wang, Wang and Gu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: MD, PhD. Wei Zhou, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, China, email@example.com