Inborn errors of metabolism detectable by tandem mass spectrometry in Beijing

Nan Yang; Li-fei Gong; Jin-qi Zhao; Hai-he Yang; Zhi-jun Ma; Wei Liu; Zhi-hui Wan; Yuan-yuan Kong

doi:10.1515/jpem-2019-0420

Article

Inborn errors of metabolism detectable by tandem mass spectrometry in Beijing

Nan Yang , Li-fei Gong , Jin-qi Zhao , Hai-he Yang , Zhi-jun Ma , Wei Liu , Zhi-hui Wan and Yuan-yuan Kong

Published/Copyright: April 17, 2020

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 33 Issue 5

Abstract

Background

Individual inborn errors of metabolism (IEMs) are rare disorders. Expanded newborn screening for IEMs by tandem mass spectrometry (TMS) is an efficient approach for early diagnosis. Here we provide the newborn screening program for the application of this approach (between July 2014 and March 2019) to the identification of newborns in Beijing at risk of developing a potentially fatal disease.

Methods

The amino acids and acylcarnitines in dried blood spots were analyzed by TMS. Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis.

Results

Among the healthy newborns, 16 metabolic disorder cases were confirmed, giving a total birth prevalence of 1:3666 live births. Organic acidemia (OA) was the most common (9/16 patients; 56%), and methylmalonic acidemia was the most frequently observed OA (7/9 patients; 89%). Five infants were diagnosed with methylmalonic acidemia with homocystinuria type CblC, two with isolated methylmalonic acidemia, one with propionic acidemia, and one with isovaleric acidemia. Four patients (4/16, 25%) were diagnosed with hyperphenylalaninemia. One suffered with medium-chain acyl CoA dehydrogenase deficiency, one with carnitine uptake deficiency, and one with citrin deficiency. Eleven cases underwent genetic analysis. Seventeen mutations in eight IEM-associated genes were identified in 11 confirmed cases. Symptoms were already present within 2 days after birth in 44% (7/16) cases. The infant with propionic acidemia died at 7 days after birth. The other cases received timely diagnosis and treatment, and most of them grew well.

Conclusions

The results illustrate challenges encountered in disease management highlighting the importance of newborn screening for inherited metabolic disorders, which is not yet nationally available in our country. Regional newborn screening programs will provide a better estimation of the incidence of IEM.

Keywords: inborn errors of metabolism; newborn screening; tandem mass spectrometry

Corresponding author: Yuan-yuan Kong, MD, PhD, Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No. 251, Yao Jia Yuan Road, Chaoyang District, Beijing 100026, P.R. China, Phone: +8610-52275310; +8610-52275314, Fax: +8610-85979592

Acknowledgments

We thank all of the project participants for their contributions. The authors would like to acknowledge MyGenostics (Beijing, China) for performing molecular testing on these patients and for providing technical support.

Author contributions: Zhi-jun Ma, Wei Liu, and Zhi-hui Wan performed the metabolic analyses, i.e. GC-MS and MS/MS analysis. Li-fei Gong and Jin-qi Zhao performed the genetic analysis. Nan Yang, Hai-he Yang, and Yuan-yuan Kong collected the samples and clinically evaluated the patients. Nan Yang wrote the manuscript.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Conflict of interest: The authors declare that there is no conflict of interest.

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Received: 2019-09-10

Accepted: 2020-02-06

Published Online: 2020-04-17

Published in Print: 2020-05-26

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Articles in the same Issue

https://doi.org/10.1515/jpem-2019-0420

Keywords for this article

inborn errors of metabolism; newborn screening; tandem mass spectrometry