AB099. Beta ketothiolase deficiency: phenotype and genotype in Vietnam population

Background and objective: Beta ketothiolase (T2) deficiency is rare inherited metabolic disease worldwide. But it is the most common organic aciduria in Vietnam with 35 cases. To describe phenotypes, genotypes of T2 deficiency.

Methods: Descriptive study of 35 patients with T2 deficiency at National Hospital of Pediatrics-Hanoi-Vietnam from 2005 to 2012. A total of 21 cases from 19 families were analyzed of T2 gene.

Results: A total of 35 patients were born to 30 unrelated families and unconsanguinity parents. And 33/35 patients presented crisis of ketone acidosis. One case was diagnosed without symptom at 3 days of age but developed the crisis at 6 months of age. One case was asymptomatic until now (5 years old). Mean onset of the first crisis was 13.1 months. Clinical features of the crises were dehydration, tarchypnea, lethargy/coma and triggered by infections. Laboratory of the crises showed 100% severe ketone metabolic acidosis (pH: 6.5-7.05), leukocytosis. 94% cases recovered from the 1st crisis and 79% cases had normal development. A total of 20/35 patients had recurrent crisis. And 21/21 patients were found homozygous/compound heterozygous mutations of T2 gene. Five different mutations have been identified: R208X; IVS10-1g>c; A410V; 163_167del5ins2; c.1032-103 INS A. And R208X is the most common mutation in Vietnam (70% of mutant allele) as well as in the world.

Conclusions: The biggest T2 deficiency patients were identified in a Vietnam center (account 1/3 total cases in the world). Worldwide, there are no common mutations of T2 gene found except common R208X mutation in Vietnam.

Keywords: Beta ketothiolase deficiency; mitochondrial acetoacetyl CoA thiolase deficiency; T2 deficiency