Please wait a minute...
Clinical and Experimental Obstetrics & Gynecology  2020, Vol. 47 Issue (4): 617-619    DOI: 10.31083/j.ceog.2020.04.5323
Case Report Previous articles | Next articles
Methylmalonic acidemia in prenatal diagnosis
B.F. Zhou1, C.X. Duan2, D.L. Tang3, *()
1Department of Obstetrics, Maternal and Child Health Hospital of Shiyan, Shiyan, Hubei, P.R. China
2Department of Otolaryngology Head and Neck Surgery, Maternal and Child Health Hospital of Hubei Province, Wuhan, Hubei, P.R. China
3Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China
Download:  PDF(407KB)  ( 196 ) Full text   ( 9 )
Export:  BibTeX | EndNote (RIS)      
Abstract  

Objective: The objective of this study was to report the prenatal diagnosis for methylmalonic acidemia. Materials and Methods: Isolated methylmalonic acidemia was diagnosed by analyzing organic acids in the blood and urine. The specific subtype of methylmalonic acidemia was determined by molecular genetic testing. Prenatal diagnosis for methylmalonic acidemia includes ultrasound examination, conventional karyotyping using cultured amniocytes, chromosomal microarray analysis, and targeted sequencing using uncultured amniocytes. Results: We identified a novel mutation (NM_172250.2; c.491G>A) in the MMAA gene that might be associated with methylmalonic acidemia. The fetus and her father are both carriers of this mutation. Conclusion: A combination of prenatal ultrasound, conventional karyotyping, chromosomal microarray analysis, and target sequencing will provide a more accurate risk assessment for methylmalonic acidemia.

Key words:  Isolated methylmalonic academia      Prenatal diagnosis      Chromosomal microarray analysis      Inherited metabolic disorder      Targeted sequencing     
Submitted:  09 July 2019      Accepted:  16 October 2019      Published:  15 August 2020     
Fund: 81773444/National Science Foundation of China under Grant
*Corresponding Author(s):  D.L. Tang     E-mail:  xuzhenzhen2002@163.com

Cite this article: 

B.F. Zhou, C.X. Duan, D.L. Tang. Methylmalonic acidemia in prenatal diagnosis. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(4): 617-619.

URL: 

https://ceog.imrpress.com/EN/10.31083/j.ceog.2020.04.5323     OR     https://ceog.imrpress.com/EN/Y2020/V47/I4/617

Figure 1.  — The genetic analysis result of the family. Ⅰ: First child Ⅱ: Father Ⅲ: Mother Ⅳ: Fetus.

[1] Dobson C.M., Wai T., Leclerc D., Wilson A., Wu X., Doré C., et al.: “Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements”. Proc Natl Acad Sci U S A, 2002, 99, 15554-15559.
doi: 10.1073/pnas.242614799 pmid: 12438653
[2] Matsui S.M., Mahoney M.J., Rosenberg L.E.: “The natural history of the inherited methylmalonic acidemias”. N Engl J Med, 1983, 308, 857-861.
doi: 10.1056/NEJM198304143081501 pmid: 6132336
[3] Han L.S., Huang Z., Han F., Ye J., Qiu W.J., Zhang H.W., et al.: “Clinical features and MUT gene mutation spectrum in Chinese patients with isolated methylmalonic acidemia: identification of ten novel allelic variants”. World J Pediatr, 2015, 11, 358-365.
doi: 10.1007/s12519-015-0043-1 pmid: 26454439
[4] Dobson C.M., Wai T., Leclerc D., Kadir H., Narang M., Lerner-Ellis J.P., et al.: “Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria”. Hum Mol Genet, 2002, 11, 3361-3369.
doi: 10.1093/hmg/11.26.3361 pmid: 12471062
[5] Yang X., Sakamoto O., Matsubara Y., Kure S., Suzuki Y., Aoki Y., et al.: “Mutation analysis of the MMAA and MMAB genes in Japanese patients with vitamin B 12-responsive methylmalonic acidemia: identification of a prevalent MMAA mutation”. Mol Genet Metab, 2004, 82, 329-333.
doi: 10.1016/j.ymgme.2004.05.002 pmid: 15308131
[6] Richards C.S., Bale S., Bellissimo D.B., Das S., Grody W.W., Hegde M.R., et al.: “ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007”. Genet Med, 2008, 10, 294-300.
doi: 10.1097/GIM.0b013e31816b5cae pmid: 18414213
[7] Splinter K., Niemi A.K., Cox R., Platt J., Shah M., Enns G.M., et al.: “Impaired health-related quality of life in children and families affected by methylmalonic acidemia”. J Genet Couns, 2016, 25, 936-944.
doi: 10.1007/s10897-015-9921-x pmid: 26667650
[8] Imtiaz F., Al-Mubarak B.M., Al-Mostafa A., Al-Hamed M., Allam R., Al-Hassnan Z., et al.: “Spectrum of mutations in 60 Saudi patients with mut methylmalonic acidemia”. JIMD Rep, 2016, 29, 39-46.
doi: 10.1007/8904_2014_297 pmid: 26615597
[9] Devi A.R.R., and Naushad S.M.: “Targeted exome sequencing for the identification of complementation groups in methylmalonic aciduria: a south Indian experience”. Clin Biochem, 2017, 50, 68-72.
doi: 10.1016/j.clinbiochem.2016.08.016 pmid: 27591164
[1] Y.J. Wu, C.J. Yu, W.H. Tian, Z. Xu. Prenatal diagnosis and molecular cytogenetic characterization of two hereditary chromosomal duplications with favorable outcomes[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(5): 789-791.
[2] D. Lu, D. Cao, Q. Zhao, X. Chen. Prenatal diagnosis and genetic counseling of mosaicism for chromosome t (7; 14) with a favorable outcome[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(3): 427-428.
[3] W.B. Wang, Q. Wu, Y. Zhou, X. Zhong, Y. Ge, J. Zhang. A 10-year retrospective study on prenatal cytogenetic analyses[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(2): 248-252.
[4] Q.C. Wu, W.B. Wang, L. Sun, Y.S. Xu, X.J. Xie, X.M. Ma, Z.Y. Su. Mutation analysis of the fibroblast growth factor receptor 3 gene in fetuses with thanatophoric dysplasia, type I[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(1): 7-11.
[5] G. Szabó, J. Rigó Jr.. Prenatal ultrasound diagnosis of abdominal pregnancy of ovarian origin[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(6): 977-979.
[6] W. Homola, M. Zimmer. Safety of amniocentesis in normal pregnancies and pregnancies considered high-risk due to fetal genetic anomalies – an observational study[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(3): 403-407.
[7] D.Y. Ma, G. Liu, C.Y. Luo, A. Liu, J.J. Zhang, P. Hu, J. Cheng, Y.G. Wang, T. Jiang, J.F. Xu. A novel mutation in the mutations in the methyl-CpG-binding protein 2 (MECP2) gene in a Chinese patient with typical Rett syndrome and subsequent prenatal diagnosis[J]. Clinical and Experimental Obstetrics & Gynecology, 2018, 45(6): 924-929.
[8] S. G. Erzincan, N. C. Sayin, C. Inan, M. A. Yuce, F. G. Varol, S. Basaran. Cell-free DNA testing: is it reliable? A case report[J]. Clinical and Experimental Obstetrics & Gynecology, 2018, 45(6): 939-941.
[9] Bo Wang, Dan Lu, Zuliang Shi, Jian Ke, Qi Zhao, Hongjun Li. Prenatal diagnosis of a complex chromosomal rearrangement involving five chromosomes[J]. Clinical and Experimental Obstetrics & Gynecology, 2018, 45(5): 797-799.
[10] Sun Young Jung, Yong Teak Oh, Suk Young Kim. Predict pregnancy outcomes of prenatal megaureter by prenatal ultrasonography[J]. Clinical and Experimental Obstetrics & Gynecology, 2018, 45(4): 544-548.
[11] G. Capobianco, G. Virdis, C. Cherchi, A. Gulotta, P.L. Cherchi, S. Dessole. Diagnosis and management of fetal omphalocele: a case report[J]. Clinical and Experimental Obstetrics & Gynecology, 2018, 45(1): 129-131.
[12] J. Han, X. Liu, Y. Zhao, Y. Zhang, L. Sun, X. Gu, X. Yang, Y. Li, Y. He. Prenatal diagnosis of absent pulmonary valve syndrome: results of a single-center experience in Beijing[J]. Clinical and Experimental Obstetrics & Gynecology, 2017, 44(6): 834-838.
[13] L.J. Kong, L. Fan, G.H. Li, W.Y. Zhang. Prevalence of congenital malformations during pregnancy in China: screening by ultrasound examination[J]. Clinical and Experimental Obstetrics & Gynecology, 2017, 44(5): 772-776.
[14] L. Zhen, A.H. Wu, C. Liao, D.Z. Li. Prediction of homozygous α-thalassemia-1 by nuchal translucency measurement at first trimester: is it possible?[J]. Clinical and Experimental Obstetrics & Gynecology, 2017, 44(4): 545-547.
[15] K.H. Gou, X.C. Gao, L. Wang, A.Q. Yan, L. Xue, S. Han, L. Yang. Risk factors for perinatal birth defects in Zhangye: a long-term hospital-based study[J]. Clinical and Experimental Obstetrics & Gynecology, 2017, 44(4): 581-583.
No Suggested Reading articles found!