A new patient with hyperornithinaemia, hyperammonaemia and homocitrullinuria treated early with low protein diet

Gjessing, L. R.; Lunde, Hilde; T, Undrum; Broch, H; Alme, A.; Lie, Sverre O.

doi:10.1007/bf01799457

Cited by 9 publications

(2 citation statements)

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“…We additionally included data from two unreported patients, recently diagnosed and managed at Children's Research Hospital Bambino Gesù, Rome, Italy (patients 110 and 111); written informed consent was obtained from the caregivers of these two patients for publication of their clinical and biochemical data. Patients n. 10,19,25,49,51,52, and 94 were monitored longitudinally in the same institution.…”

Section: Methodsmentioning

confidence: 99%

Hyperornithinemia, hyperammonemia, homocitrullinuria syndrome

Nyhan¹,

Hoffmann²,

Al-Aqeel³

et al. 2020

Atlas of Inherited Metabolic Diseases

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Background: Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive disorder of the urea cycle. HHH has a panethnic distribution, with a major prevalence in Canada, Italy and Japan. Acute clinical signs include intermittent episodes of vomiting, confusion or coma and hepatitis-like attacks. Alternatively, patients show a chronic course with aversion for protein rich foods, developmental delay/intellectual disability, myoclonic seizures, ataxia and pyramidal dysfunction. HHH syndrome is caused by impaired ornithine transport across the inner mitochondrial membrane due to mutations in SLC25A15 gene, which encodes for the mitochondrial ornithine carrier ORC1. The diagnosis relies on clinical signs and the peculiar metabolic triad of hyperammonemia, hyperornithinemia, and urinary excretion of homocitrulline. HHH syndrome enters in the differential diagnosis with other inherited or acquired conditions presenting with hyperammonemia. Methods: A systematic review of publications reporting patients with HHH syndrome was performed.Results: We retrospectively evaluated the clinical, biochemical and genetic profile of 111 HHH syndrome patients, 109 reported in 61 published articles, and two unpublished cases. Lethargy and coma are frequent at disease onset, whereas pyramidal dysfunction and cognitive/behavioural abnormalities represent the most common clinical features in late-onset cases or during the disease course. Two common mutations, F188del and R179* account respectively for about 30% and 15% of patients with the HHH syndrome. Interestingly, the majority of mutations are located in residues that have side chains protruding into the internal pore of ORC1, suggesting their possible interference with substrate translocation. Acute and chronic management consists in the control of hyperammonemia with protein-restricted diet supplemented with citrulline/arginine and ammonia scavengers. Prognosis of HHH syndrome is variable, ranging from a severe course with disabling manifestations to milder variants compatible with an almost normal life. Conclusions:This paper provides detailed information on the clinical, metabolic and genetic profiles of all HHH syndrome patients published to date. The clinical phenotype is extremely variable and its severity does not correlate with the genotype or with recorded ammonium/ornithine plasma levels. Early intervention allows almost normal life span but the prognosis is variable, suggesting the need for a better understanding of the still unsolved pathophysiology of the disease.

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Section: Methodsmentioning

confidence: 99%

Hyperornithinemia, hyperammonemia, homocitrullinuria syndrome

Nyhan¹,

Hoffmann²,

Al-Aqeel³

et al. 2020

Atlas of Inherited Metabolic Diseases

View full text Add to dashboard Cite

show abstract

“…9 However, patients with HHH syndrome can respond well to a low-protein diet with improvements in neurological symptoms and hepatic function, for which reason an accurate diagnosis is critical to management. 5,10 For the first time in Hong Kong, here we describe HHH syndrome in a pair of siblings and their clinical, biochemical, and molecular profiles, with a view to facilitate understanding of this disorder in our At the age of 11 months, gas chromatographymass spectrometry of urine detected significant hyperexcretion of uracil and moderately excessive excretion of orotic acid, while he was taking an unrestricted protein diet (approximately 3 g/kg/day). He also had homocitrullinuria of up to 71 (reference level, <9) μmol/mmol creatinine, which was also demonstrated by liquid chromatography-tandem mass spectrometry.…”

Section: 高鳥胺酸血症-高氨血症-高瓜胺酸血綜合症：一種可治癒但須及早診斷的遺傳性肝臟病mentioning

confidence: 99%