Hyperornithinemia–Hyperammonemia–Homocitrullinuria Syndrome in Vietnamese Patients
Khanh Ngoc Nguyen,
Van Khanh Tran,
Ngoc Lan Nguyen,
Thi Bich Ngoc Can,
Thi Kim Giang Dang,
Thu Ha Nguyen,
Thi Thanh Mai Do,
Le Thi Phuong,
Thinh Huy Tran,
Thanh Van Ta,
Nguyen Huu Tu,
Chi Dung Vu
Affiliations
Khanh Ngoc Nguyen
Center of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children’s Hospital, 18/879 La Thanh, Dong Da, Hanoi 11512, Vietnam
Van Khanh Tran
Center for Gene and Protein Research, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam
Ngoc Lan Nguyen
Center for Gene and Protein Research, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam
Thi Bich Ngoc Can
Center of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children’s Hospital, 18/879 La Thanh, Dong Da, Hanoi 11512, Vietnam
Thi Kim Giang Dang
Center of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children’s Hospital, 18/879 La Thanh, Dong Da, Hanoi 11512, Vietnam
Thu Ha Nguyen
Center of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children’s Hospital, 18/879 La Thanh, Dong Da, Hanoi 11512, Vietnam
Thi Thanh Mai Do
Center of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children’s Hospital, 18/879 La Thanh, Dong Da, Hanoi 11512, Vietnam
Le Thi Phuong
Center for Gene and Protein Research, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam
Thinh Huy Tran
Biochemistry Department, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam
Thanh Van Ta
Biochemistry Department, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam
Nguyen Huu Tu
Hanoi Medical Univerity Hospital, Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11521, Vietnam
Chi Dung Vu
Center of Endocrinology, Metabolism, Genetic/Genomics and Molecular Therapy, Vietnam National Children’s Hospital, 18/879 La Thanh, Dong Da, Hanoi 11512, Vietnam
Background and Objectives: Hyperornithinemia–hyperammonemia–homocitrullinuria syndrome (HHH; OMIM 238970) is one of the rare urea cycle disorders. Ornithine carrier 1 deficiency causes HHH syndrome, characterized by failure of mitochondrial ornithine uptake, hyperammonemia, and accumulation of ornithine and lysine in the cytoplasm. The initial presentation and time of diagnosis in HHH highly varies. Genetic analysis is critical for diagnosis. Materials and Methods: This study encompassed retrospective and prospective analyses of four unrelated Vietnamese children diagnosed with HHH syndrome. Results: The age of diagnosis ranged from 10 days to 46 months. All four cases demonstrated hyperornithinemia and prolonged prothrombin time. Three out of four cases presented with hyperammonemia, elevated transaminases, and uraciluria. No homocitrulline was detected in the urine. Only one case depicted oroticaciduria. Genetic analyses revealed three pathogenic variants in the SLC25A15 gene, with the c.535C>T (p.Arg179*) variant common in Vietnamese patients. The c.562_564del (p.Phe188del) and c.408del (p.Met137Cysfs*10) variants were detected in one case. The latter variant has yet to be reported in the literature on HHH patients. After intervention with a protein-restricted diet, ammonia-reducing therapy, and L-carnitine supplementation, hyperammonemia was not observed, and liver enzyme levels returned to normal. Conclusions: Our results highlighted the clinical and biochemical heterogeneity of HHH syndrome and posed that HHH syndrome should be considered when individuals have hyperammonemia, elevated transaminase, and decreased prothrombin time.
