OBJECTIVE

Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase deficiency due to GCDH gene mutations. In this study, the clinical presentation and molecular aspects of 23 Chinese patients (11 males and 12 females) were investigated.

METHODS

All patients were diagnosed by elevated urinary glutaric acid and GCDH gene analysis. Protein-restricted diet supplemented with special formula, l-carnitine and GABA analog were initialed after diagnosis. The clinical and biochemical features were analyzed. Mutational analysis of GCDH was conducted.

RESULTS

Clinical manifestations of 23 patients varied from asymptomatic to severe encephalopathy, with notable phenotypic differences between siblings with the same mutations. One case was detected by newborn screening, while 22 Cases were diagnosed between the ages of 5 months and 51 years. 29 mutations in GCDH were identified. Among them, 11 were novel, including seven missense mutations (c.406G > T, C.416C > G, c.442G > A, c.640A > G, c.901G > A, c.979G > A, and c.1207C > T), three frameshift mutations (c.873delC, c.1172-1173insT and c.1282-1285ins71) and one nonsense mutation (c.411C > G). In exon 5, c.553G > A and c.148T > C were found in four alleles (8.7%) and three alleles (6.5%) of the patients, respectively.

CONCLUSIONS

In 23 Chinese patients with GA1, 11 novel GCDH mutations were identified. This may indicate that the genetic profiles of Chinese patients are different from those of other populations.

SYNOPSIS

23 Chinese GA1 patients with varied clinical manifestations have been reported. 11 novel mutations in their GCDH gene were identified, indicating that the genetic profiles of Chinese GA1 patients differ from those of other populations.