Analysis of clinical features and GCDH gene mutations in four patients with glutaric academia type I.
- Author:
Peng -qiang WEN
1
;
Guo-bing WANG
;
Xiao-hong LIU
;
Zhan-ling CHEN
;
Yue SHANG
;
Dong CUI
;
Ping SONG
;
Quan YUAN
;
Shu-li CHEN
;
Jian-xiang LIAO
;
Cheng-rong LI
Author Information
- Publication Type:Case Reports
- MeSH: Amino Acid Metabolism, Inborn Errors; diagnosis; genetics; metabolism; Amino Acid Sequence; Base Sequence; Brain Diseases, Metabolic; diagnosis; genetics; metabolism; Glutaryl-CoA Dehydrogenase; deficiency; genetics; metabolism; Humans; Infant; Male; Molecular Sequence Data; Mutation; Sequence Alignment
- From: Chinese Journal of Medical Genetics 2012;29(6):642-647
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo review clinical features of four male patients with glutaric academia type I and screen glutaryl-CoA dehydrogenase (GCDH) gene mutations.
METHODSThe 4 patients underwent brain computer tomography (CT) and magnetic resonance imaging (MRI) analyses. Blood acylcarnitine and urine organic acid were analyzed with tandem mass spectrometry and gas chromatographic mass spectrometry. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of GCDH gene were amplified with PCR and subjected to direct DNA sequencing.
RESULTSAll patients have manifested macrocephaly, with head circumference measured 50 cm (14 months), 47 cm (9 months), 46 cm (5 months) and 51 cm (14 months), respectively. Imaging analyses also revealed dilation of Sylvian fissure and lateral ventricles, frontotemporal atrophy, subarachnoid space enlargement and cerebellar vermis abnormalities. All patients had elevated glutarylcarnitine (5.8 umol/L, 7.5 umol/L, 8.3 umol/L and 7.9 umol/L, respectively) and high urinary excretion of glutaric acid. Seven mutations were identified among the patients, among which c.146_149del4, IVS6-4_Ex7+4del8, c.508A>G (p.K170E), c.797T>C (p.M266T) and c.420del10 were first discovered.
CONCLUSIONMacrocephaly and neurological impairment are the most prominent features of glutaric academia type I. Blood tandem mass spectrometry and urine gas chromatographic mass spectrometry analysis can facilitate the diagnosis. The results can be confirmed by analysis of GCDH gene mutations.
