Please wait a minute...
J Zhejiang Univ (Med Sci)  2021, Vol. 50 Issue (6): 795-798    DOI: 10.3724/zdxbyxb-2021-0262
A case of methylmalonic acidemia and homocysteinemia cblX type with negative tandem mass spectrometry testing
SHEN Yaping,HU Zhenzhen,YANG Jianbin,YANG Rulai,HUANG Xinwen()
Department of Genetics and Metabolism, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China
Download: HTML( 10 )   PDF(2268KB)
Export: BibTeX | EndNote (RIS)      


A child with methylmalonic acidemia and homocysteinemia cblX type presented focal seizures and epileptic spasms in early infancy, but the tandem mass spectrometry tests showed negative results during neonatal screening or acute attack. Despite treated with a variety of antiepileptic drugs, the child died at age of 4?months. The blood spot sample of the patient was retrospectively tested with ultrahigh performance liquid chromatography-tandem mass spectrometry, and the increased levels of methylmalonic acid and homocysteine were revealed. Whole exome sequencing showed that the proband had a c.202C>G(p.Q68E) hemizygous mutation inHCFC1 gene, which was inherited from his mother.

Key wordsMetabolism, inborn errors      Methylmalonic acidemia      Homocysteinemia cblX type      Diagnosis      Ultrahigh performance liquid chromatography      Tandem mass spectrometry      Case reports     
Received: 09 April 2021      Published: 22 March 2022
CLC:  R725.8  
Corresponding Authors: HUANG Xinwen     E-mail:
Cite this article:

SHEN Yaping,HU Zhenzhen,YANG Jianbin,YANG Rulai,HUANG Xinwen. A case of methylmalonic acidemia and homocysteinemia cblX type with negative tandem mass spectrometry testing. J Zhejiang Univ (Med Sci), 2021, 50(6): 795-798.

URL:     OR



关键词: 代谢缺陷, 先天性,  甲基丙二酸血症,  同型半胱氨酸血症cblX型,  诊断,  超高效液相色谱法,  串联质谱法,  病例报告 
Figure1 Sequencing diagram of the gene in this pedigree
[1]   YU H C, SLOAN J L, SCHARER G, et al.An X-linked cobalamin disorder caused by mutations in transcriptional coregulator HCFC1[J]Am J Hum Genet, 2013, 93( 3): 506-514.
doi: 10.1016/j.ajhg.2013.07.022
[2]   CASTRO V L, QUINTANA A M. The role of HCFC1 in syndromic and non-syndromic intellectual disability[J]Med Res Arch, 2020, 8( 6): 10.18103/mra.v8i6.2122.
doi: 10.18103/mra.v8i6.2122
[3]   GéRARD M, MORIN G, BOURILLON A, et al.Multiple congenital anomalies in two boys with mutation in HCFC1 and cobalamin disorder[J]Eur J Med Genet, 2015, 58( 3): 148-153.
doi: 10.1016/j.ejmg.2014.12.015
[4]   QUINTANA A M, YU H C, BREBNER A, et al.Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities[J]Hum Mol Genet, 2017, 26( 15): 2838-2849.
doi: 10.1093/hmg/ddx157
[5]   JOLLY L A, NGUYEN L S, DOMINGO D, et al.HCFC1 loss-of-function mutations disrupt neuronal and neural progenitor cells of the developing brain[J]Hum Mol Genet, 2015, 24( 12): 3335-3347.
doi: 10.1093/hmg/ddv083
[6]   KOUFARISC, ALEXANDROUA, TANTELESG A, et al.A novel HCFC1 variant in male siblings with intellectual disability and microcephaly in the absence of cobalamin
doi: 10.3892/br.2015.559
[7]   HUANG L, JOLLY L A, WILLIS-OWEN S, et al.A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability[J]Am J Hum Genet, 2012, 91( 4): 694-702.
doi: 10.1016/j.ajhg.2012.08.011
[8]   SCALAIS E, OSTERHELD E, WEITZEL C, et al.X-linked cobalamin disorder (HCFC1) mimicking nonketotic hyperglycinemia with increased both cerebrospinal fluid glycine and methylmalonic acid[J]Pediatr Neurol, 2017, 65-69.
doi: 10.1016/j.pediatrneurol.2016.12.003
[9]   PITON A, GAUTHIER J, HAMDAN F F, et al.Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia[J]Mol Psychiatry, 2011, 16( 8): 867-880.
doi: 10.1038/mp.2010.54
[10]   TARPEY P S, SMITH R, PLEASANCE E, et al.A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation[J]Nat Genet, 2009, 41( 5): 535-543.
doi: 10.1038/ng.367
[11]   李东晓, 刘玉鹏, 丁 圆, 等. 转录辅助调节因子HCFC1突变致罕见X连锁甲基丙二酸尿症CblX型一家系报告[J]. 临床儿科杂志, 2016, 34(3): 212-216
LI Dongxiao, LIU Yupeng, DING Yuan, et al. A pedigree of a rare Cb1X type X-linked methylmalonic acidemia due to transcriptional co-regulator HCFC1 mutation[J]. Journal of Clinical Pediatrics, 2016,
[1] YU Yue,LING Shiying,SHUAI Ruixue,QIU Wenjuan,ZHANG Huiwen,LIANG Lili,JI Wenjun,LIU Yuchao,GU Xuefan,HAN Lianshu. Clinical features and outcomes of patients with cblC type methylmalonic acidemia carrying MMACHC gene c.609G>A mutation[J]. J Zhejiang Univ (Med Sci), 2021, 50(4): 436-443.
[2] ZHOU Duo,YE Meiling,HU Zhenzhen,ZHANG Yu,ZHU Lin,YANG Rulai,HUANG Xinwen. Screening of multiple acyl-CoA dehydrogenase deficiency in newborns and follow-up of patients[J]. J Zhejiang Univ (Med Sci), 2021, 50(4): 454-462.
[3] TANG Chengfang,TAN Minyi,XIE Ting,TANG Fang,LIU Sichi,WEI Qingxiu,LIU Jilian,HUANG Yonglan. Screening for neonatal inherited metabolic disorders by tandem mass spectrometry in Guangzhou[J]. J Zhejiang Univ (Med Sci), 2021, 50(4): 463-471.
[4] YANG Chiju,SHI Caihong,ZHOU Cheng,WAN Qiuhua,ZHOU Yanbin,CHEN Xigui,JIN Xianlian,HUANG Chenggang,XU Peng. Screening and follow-up results of fatty acid oxidative metabolism disorders in 608 818 newborns in Jining, Shandong province[J]. J Zhejiang Univ (Med Sci), 2021, 50(4): 472-480.
[5] WANG Yanmin,TIAN Guoli,JI Wei,WANG Simei,ZHANG Xiaofen. Very long chain acylcarnitines and lysophosphatidylcholines in screening of peroxisomal disease in children by tandem mass spectrometry[J]. J Zhejiang Univ (Med Sci), 2021, 50(4): 481-486.
[6] KUANG Wenjing,LUO Xiaobo,WANG Jiongke,ZENG Xin. Research progress on Melkersson-Rosenthal syndrome[J]. J Zhejiang Univ (Med Sci), 2021, 50(2): 148-154.
[7] CHEN Qianming,LI Zaiye,ZENG Xin. Diagnostic strategies for oral manifestations of infectious diseases[J]. J Zhejiang Univ (Med Sci), 2021, 50(2): 141-147.
[8] LIU Chuanxia,CHEN Qianming. Clinical diagnosis of oral erosive and ulcerative diseases in children[J]. J Zhejiang Univ (Med Sci), 2021, 50(2): 155-161.
[9] ZHANG Yuting,YUAN Peiyang,JIANG Han,QIU Xuemei,WANG Jiongke,LUO Xiaobo,DAN Hongxia,ZHOU Yu,ZENG Xin,JIANG Lu,CHEN Qianming. Application of medical magnifying loupes in diagnosis of oral mucosal diseases[J]. J Zhejiang Univ (Med Sci), 2021, 50(2): 205-211.
[10] YAN Jing,ZHANG Tingting,ZHAO Kui. Application of molecular probes in nuclear imaging of neuroendocrine tumors[J]. J Zhejiang Univ (Med Sci), 2021, 50(1): 131-137.
[11] WANG Subo,ZHAO Zhenhua,ZHANG Yu,YANG Liming,HUANG Yanan,RUAN Yawen,WANG Cheng. Quantitative perfusion histogram parameters of dynamic contrast-enhanced MRI to identify different pathological types of uterine leiomyoma[J]. J Zhejiang Univ (Med Sci), 2021, 50(1): 97-105.
[12] HU Zhenzhen,YANG Jianbin,HU Lingwei,ZHAO Yunfei,ZHANG Chao,YANG Rulai,HUANG Xinwen. Screening and clinical analysis of isovaleric acidemia newborn in Zhejiang province[J]. J Zhejiang Univ (Med Sci), 2020, 49(5): 556-564.
[13] JIN Xiaoxiao,JIN Pengzhen,YAN Kai,QIAN Yeqing,DONG Minyue. Genetic analysis of a mosaic case with low proportion mutation of TSC2 gene[J]. J Zhejiang Univ (Med Sci), 2020, 49(5): 586-590.
[14] DUAN Runping,XU Yesheng,ZHENG Libin,YAO Yufeng. Research progress on etiologic diagnosis of ocular viral diseases[J]. J Zhejiang Univ (Med Sci), 2020, 49(5): 644-650.
[15] Division of Genetics and Metabolism, Child Diseases and Health Care Branch, Chinese Association for Maternal and Child Health . Consensus on diagnosis and treatment of ornithine trans-carbamylase deficiency[J]. J Zhejiang Univ (Med Sci), 2020, 49(5): 539-547.