Study on Inherited Endocrine and Metabolic Disease
Clinical diagnosis and treatment of three cases with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
Hanzhou Guan, Yuan Ding, Dongxiao Li, Hui Dong, Jinqing Song, Ying Jin, Zhijun Zhu, Liying Sun, Yanling Yang
Published 2017-06-02
Cite as Chin J Pediatr, 2017, 55(6): 428-433. DOI: 10.3760/cma.j.issn.0578-1310.2017.06.007
Abstract
ObjectiveTo study the clinical characteristics, methods of diagnosis and treatment of hyperornithinemia-hyperammonemia- homocitrullinuria (HHH) syndrome.
MethodFrom July 2011 to August 2016, 3 Chinese patients with HHH syndrome were enrolled in this study. The clinical course, biochemical features, brain MRI findings, and gene mutations were analyzed.
ResultThe three patients′ age at onset of symptoms was 3 months to 7 years, and the age of diagonosis was 3 years and 10 months to 9 years and 10 months. All of them presented with intolerance to protein-rich foods from the infant period, development retardation and abnormal posture. Case 1 and 2 had moderate mental retardation. Serum ammonia 25-276 μmol/L (reference range<60 μmol/L), alanine aminotransferase (ALT) 20-139 IU/L (reference range 9-50 IU/L), ornithine 29.12-99.44 μmol/L(reference range 15-100 μmol/L), urinary orotic acid 1.49-29.75 mmol/mol Cr (reference range 0-7 mmol/mol Cr), uracil 6.09-103.97 mmol/mol Cr (reference range 0-1.5 mmol/mol Cr). The cranial MRI revealed lesions in the basal ganglia, abnormal white matter signal, progressive demyelination and cerebral atrophy. On their SLC25A15 gene, a novel homozygous missense mutation c. 416A>G (p.E139G) was identified in case 1, a known pathogenic homozygous nonsense mutation c. 535C>T was found in case 2 and 3. Liver transplantation had been performed when case 1 was 6 years old. Significant improvements were observed in dietary habit, mental and motor functions, and biochemical parameters. After the dietary intervention with the supplements of arginine, L-carnitine, case 2 was improved, spastic paraplegia of case 3 had no mitigation. Liver transplant was recommended.
ConclusionHHH syndrome has an aversion to protein-rich food, and the patients have recurrent vomiting and progressive neurological dysfunction. Clinical diagnosis of HHH syndrome is difficult and patients may present with incomplete biochemical phenotype. The genetic analysis is key for the diagnosis. Depending on their condition, individuals with HHH syndrome can be treated with a low-protein diet, drugs and liver transplantation.
Key words:
HHH syndrome; SLC25A15; Urea cycle disorder, inborn; Ornithine transporter
Contributor Information
Hanzhou Guan
Department of Neonatology, Shanxi Provincial Children′s Hospital, Taiyuan 030013, China
Yuan Ding
Dongxiao Li
Hui Dong
Jinqing Song
Ying Jin
Zhijun Zhu
Liying Sun
Yanling Yang
