Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome in Vietnamese Patients

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) is a rare genetic urea cycle disorder.
• It results from ornithine carrier 1 deficiency, impairing mitochondrial ornithine uptake and leading to hyperammonemia and amino acid accumulation.
• Clinical presentation and diagnosis timing for HHH syndrome are highly variable.

Purpose of the Study:

• To analyze the clinical and genetic characteristics of four Vietnamese children diagnosed with HHH syndrome.
• To identify pathogenic variants in the SLC25A15 gene associated with HHH in this population.
• To highlight the diagnostic challenges and treatment outcomes for HHH.

Main Methods:

• Retrospective and prospective analysis of four unrelated Vietnamese children with HHH syndrome.
• Biochemical assessments including ammonia, ornithine, lysine, and liver function tests.
• Genetic analysis to identify variants in the SLC25A15 gene.

Main Results:

• Diagnosis ages ranged from 10 days to 46 months, showing significant heterogeneity.
• All cases exhibited hyperornithinemia and prolonged prothrombin time; three had hyperammonemia and elevated transaminases.
• Three pathogenic SLC25A15 variants were identified, including a common Vietnamese variant (c.535C>T) and a novel variant (c.408del).

Conclusions:

• HHH syndrome exhibits considerable clinical and biochemical variability.
• Consider HHH in patients with hyperammonemia, elevated transaminases, and prolonged prothrombin time.
• Effective management with dietary changes and L-carnitine normalized metabolic parameters.