PMID- 32470406
OWN - NLM
STAT- MEDLINE
DCOM- 20210525
LR  - 20210525
IS  - 1873-3492 (Electronic)
IS  - 0009-8981 (Linking)
VI  - 509
DP  - 2020 Oct
TI  - Clinical, biochemical, molecular and therapeutic characteristics of four new 
      patients of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency.
PG  - 83-90
LID - S0009-8981(20)30150-9 [pii]
LID - 10.1016/j.cca.2020.04.004 [doi]
AB  - Thirty patients with mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 
      (HMGCS) deficiency, which is a rare autosomal recessive disorder caused by HMGCS2 
      gene mutation are known. Here, we present four new patients with this disease. 
      The characteristics including several metabolites of patients were recorded. 
      Next-generation targeted sequencing and multiple sequence alignment of PCR 
      amplified products allowed for mutational analysis of HMGCS2. Minigene assay 
      transcript analysis confirmed pathogenicity of a splice site mutation. All cases 
      had recurrent episodes with infections while they had no symptoms during 
      intermissions. Patient 1, a girl, showed recurrent severe metabolic acidosis 
      after infections from 8 months old and presented with weakness, vomiting and 
      lethargy but had normal blood glucose. After treatment, she revived completely. 
      Patients 2, 3 and 4 were boys who showed episodes of hypoglycemia since 8, 27 and 
      10 months of age, respectively. Glucose infusion reversed the symptoms. All four 
      patients had hepatomegaly and abdominal imaging showed fatty livers. Serum free 
      fatty acid increased. Urinary dicarboxylic acids and urinary 
      4-hydroxy-6-methyl-2pyrone presented. Diagnosis was confirmed by HMGCS2 gene 
      analysis and 7 mutations (p.R188H, p.F420S, p.R206C, IVS2 + 1G > T, p.E401*, 
      p.A450Pfs*7 and p.Q427*) of this gene were found. Here we report on the 
      characteristics and genetics of four new patients with HMGCS deficiency. This 
      study will enrich our knowledge of this rare autosomal recessive disorder.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Wang, Qiao
AU  - Wang Q
AD  - Department of Endocrinology, Genetics and Metabolism, Beijing Children's 
      Hospital, Beijing 100045, China.
FAU - Yang, Yan-Ling
AU  - Yang YL
AD  - Department of Pediatrics, Peking University First Hospital, Beijing 100034, 
      China.
FAU - Liu, Min
AU  - Liu M
AD  - Department of Endocrinology, Genetics and Metabolism, Beijing Children's 
      Hospital, Beijing 100045, China.
FAU - Chen, Jia-Jia
AU  - Chen JJ
AD  - Department of Endocrinology, Genetics and Metabolism, Beijing Children's 
      Hospital, Beijing 100045, China.
FAU - Li, Xiao-Qiao
AU  - Li XQ
AD  - Department of Endocrinology, Genetics and Metabolism, Beijing Children's 
      Hospital, Beijing 100045, China.
FAU - Cao, Bing-Yan
AU  - Cao BY
AD  - Department of Endocrinology, Genetics and Metabolism, Beijing Children's 
      Hospital, Beijing 100045, China.
FAU - Gong, Chun-Xiu
AU  - Gong CX
AD  - Department of Endocrinology, Genetics and Metabolism, Beijing Children's 
      Hospital, Beijing 100045, China. Electronic address: chunxiugong@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20200526
PL  - Netherlands
TA  - Clin Chim Acta
JT  - Clinica chimica acta; international journal of clinical chemistry
JID - 1302422
RN  - 0 (Acyl Coenzyme A)
RN  - 1553-55-5 (3-hydroxy-3-methylglutaryl-coenzyme A)
SB  - IM
MH  - *Acyl Coenzyme A/deficiency
MH  - DNA Mutational Analysis
MH  - Female
MH  - Humans
MH  - *Hypoglycemia
MH  - Infant
MH  - Male
MH  - Mutation
OTO - NOTNLM
OT  - 3-Hydroxy-3-methylglutaryl-CoA
OT  - 4-Hydroxy-6-methyl-2pyrone
OT  - HMGCS2
OT  - Hypoglycemia
OT  - Ketone biosynthesis
COIS- Declaration of Competing Interest There are no conflicts of interest.
EDAT- 2020/05/30 06:00
MHDA- 2021/05/26 06:00
CRDT- 2020/05/30 06:00
PHST- 2020/01/18 00:00 [received]
PHST- 2020/04/01 00:00 [revised]
PHST- 2020/04/04 00:00 [accepted]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2021/05/26 06:00 [medline]
PHST- 2020/05/30 06:00 [entrez]
AID - S0009-8981(20)30150-9 [pii]
AID - 10.1016/j.cca.2020.04.004 [doi]
PST - ppublish
SO  - Clin Chim Acta. 2020 Oct;509:83-90. doi: 10.1016/j.cca.2020.04.004. Epub 2020 May 
      26.