Hyperornithinemia–hyperammonemia–homocitrullinuria syndrome with stroke-like imaging presentation: Clinical, biochemical and molecular analysis

Adult-Onset Presentation of a Hyperornithinemia-Hyperammonemia-Homocitrullinuria Patient Without Prior History of Neurological Complications

“…Molecular analysis revealed that the patient carries two O R N T 1 m u t a t i o n s , p . [ G l y 22 0 A rg( + ) A rg 27 5 X ] (c.[658G>A(+)823C>T]), which have been previously described in HHH homozygous probands presenting during infancy and the early childhood period (Al-Hassnan et al 2008;Torisu et al 2006). …”

Substrate Specificity of the Two Mitochondrial Ornithine Carriers Can Be Swapped by Single Mutation in Substrate Binding Site

“…The tissue distribution of the isoforms is overlapping; they are found in most tissues with ORC1 expressed more than ORC2 especially in liver, pancreas, lung, and testis (23). Mutations of the ORC1 gene that inactivate the carrier protein and cause the autosomal recessive hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome (OMIM238970) have provided clues for the functional importance of certain residues (23)(24)(25)(26)(27). Some of the missense mutations causing HHH syndrome, such as E180K (24), G220R (25), R275Q (23,26), G27R, A70L, F188L, G216S, T272I, and L283F (27), affect residues protruding into the substrate translocation pathway of ORC1, suggesting that they might affect substrate binding (8,13,28).…”

Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome: a treatable genetic liver disease warranting urgent diagnosis

“…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.…”

“…It was later found that the clinical presentations of HHH syndrome can be highly variable, and include spastic paraplegia, pyramidal and extrapyramidal signs, stroke-like episodes, hypotonia, seizures, ataxia, protein intolerance, failure to thrive, and hepatic failure. [5][6][7] Liver biopsies typically reveal vacuolated hepatocytes distended with glycogen on light microscopy and bizarre-looking mitochondria on electronic microscopy. 8 …”