Clinical and Mutational Analysis of theGCDHGene in Malaysian Patients with Glutaric Aciduria Type 1.
Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by theGCDHgene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from infancy and diagnosed clinically from large excretion of glutaric and 3-hydroxyglutaric acids. Bidirectional sequencing of theGCDHgene revealed ten mutations, three of which were novel (Gln76Pro, Glu131Val, and Gly390Trp). The spectrum of mutations included eight missense mutations, a nonsense mutation, and a splice site mutation. Two mutations (Gln76Pro and Arg386Gln) were homozygous in two patients with parental consanguinity. All mutations were predicted to be disease causing by MutationTaster2. In conclusion, this is the first report of both clinical and molecular aspects of GA1 in Malaysian patients. Despite the lack of genotype and phenotype correlation, early diagnosis and timely treatment remained the most important determinant of patient outcome.
Molecular Diagnostics and Protein Unit, Institute for Medical Research, Kuala Lumpur, Malaysia.
Siti Aishah
0000-0002-8611-5321
SA
Abdul Wahab
Molecular Diagnostics and Protein Unit, Institute for Medical Research, Kuala Lumpur, Malaysia.
Yusnita
Y
Yakob
Molecular Diagnostics and Protein Unit, Institute for Medical Research, Kuala Lumpur, Malaysia.
Nor Azimah
NA
Abdul Azize
Biochemistry Unit, Institute for Medical Research, Kuala Lumpur, Malaysia.
Zabedah
Z
Md Yunus
Department of Genetics, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
Leong
L
Huey Yin
Molecular Diagnostics and Protein Unit, Institute for Medical Research, Kuala Lumpur, Malaysia.
Mohd Khairul Nizam
MK
Mohd Khalid
Department of Genetics, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
Ngu
N
Lock Hock
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