[Analysis of clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency].
OBJECTIVE
To investigate the clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency (BKTD).


METHODS
Clinical features and laboratory test data were collected. The probands were monozygotic twin brothers. Genomic DNA was isolated from peripheral blood leukocytes obtained from the probands and their family members. Molecular genetic testing of the ACAT1 gene was carried out.


RESULTS
The probands have presented with fever, vomiting and severe ketoacidosis. By arterial blood gas testing, pH was determined to be 7.164, bicarbonate was 4.0 mmol/L, and urine ketone was ++++. Urinary organic acid gas chromatography-mass spectrometry analysis showed excessive excretion of 3-hydroxybutyric acid, 2-methyl-3-hydroxybutyric acid and tiglylglycine. Increased 3-hydroxybutyrylcarnitine (C4-OH), tiglylcarnitine(C5:1) and 3-hydroxyisovalerylcarnitine (C5-OH) levels. The clinical phenotype of proband's parents were both normal, but an elder sister turned out to be an affected patient. Genetic analysis has identified two heterozygous mutations [c.622C>T(p.R208X) and c.653C>T (p.S218F)] in the proband, which were respectively detected in the mother and father. The c.653C>T (p.S218F) mutation was not found among the 100 healthy controls and has not been included in the Human Gene Mutation Database(HGMD).


CONCLUSIONS
The primary clinical manifestations of BKTD is ketoacidosis. Urine organic acid and blood acylcarnitine analyses play an important role in the diagnosis of the disease. The compound heterozygous of ACAT1 gene mutations probably underlie the BKTD in our patient.
Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen, Guangdong 518038, China. rogasan@163.com.
Pengqiang
P
Wen
Zhanling
Z
Chen
Guobing
G
Wang
Zhe
Z
Su
Xiuwei
X
Zhang
Gen
G
Tang
Dong
D
Cui
Xiaohong
X
Liu
Chengrong
C
Li
D000101:Acetyl-CoA C-Acetyltransferase / Q000235:genetics*; D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency* / Q000235:genetics; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D019295:Computational Biology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype
D000102:Acetyl-CoA C-Acyltransferase; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase