[Clinical and mutational features of maternal 3-methylcrotonyl coenzyme deficiency].
OBJECTIVE
To report on 5 patients with maternal 3-methylcrotonyl coenzyme A carboxylase deficiency (MCCD) and to confirm the clinical diagnosis through mutation analysis.


METHODS
Five neonates with higher blood 3-hydroxy isovalerylcarnitine (C5-OH) concentration detected upon newborn screening with tandem mass spectrometry and their mothers were recruited. Urinary organic acids were analyzed with gas chromatography mass spectrometry. Gene mutation and protein function analysis were performed by PCR direct sequencing and PolyPhen-2 software.


RESULTS
Higher blood C5-OH concentrations (5.11-21.77 μmol/L) and abnormal 3-hydroxy isovalerate and 3-methylcrotonyl glycine in urine were detected in the five asymptomatic mothers, who were diagnosed as benign MCCD. Higher C5-OH concentration was also detected in their neonates by tandem mass spectrometry, which had gradually decreased to normal levels in three neonates. Four new variations, i.e., c.ins1680A(25%), c.203C > T (p.A68V), c.572T > C (p.L191P) and c.639+5G > T were detected in the MCCC1 gene, in addition with 2 mutations [c.1406G > T (p.R469L, novel variation) and c.592C > T (p.Q198X)]. The novel variations were predicted to have affected protein structure and function.


CONCLUSIONS
For neonates with higher C5-OH concentration detected upon neonatal screening, their mothers should be also tested to rule out MCCD. Mutations in MCCC1 gene are quite common.
Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P. R. China. Email: yejun2314@yahoo.com.cn.
Li-fei
LF
Gong
Jun
J
Ye
Lian-shu
LS
Han
Wen-juan
WJ
Qiu
Hui-wen
HW
Zhang
Xiao-lan
XL
Gao
Jing
J
Jin
Hao
H
Xu
Xue-fan
XF
Gu
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D019735:Carbon-Carbon Ligases / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D015997:Neonatal Screening; D012737:Sex Factors; D053719:Tandem Mass Spectrometry; D056806:Urea Cycle Disorders, Inborn / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*
C098116:3-hydroxyisovalerylcarnitine; D019735:Carbon-Carbon Ligases; C021573:methylcrotonoyl-CoA carboxylase; D002331:Carnitine