Hyperornithinemia

Hcit homocitrulline, Hey homocysteine, HHH hyperornithinemia-hyperammonemia-homocitrullinemia, His histidine,... 

Lysine Urea cycle defects Organic acidemias Hyperornithinemia... 

Consideration of other plasma amino acids also informs the diagnosis of inborn errors of urea synthesis. The plasma concentrations of glutamine and alanine are often elevated in parallel with or prior to the ammonium concentration as they act as a nitrogen buffer. Plasma arginine concentrations are low since the only synthetic route for arginine in humans is via the urea cycle. In contrast, the arginine concentration is elevated in ARG-1 deficiency. Hyperornithinemia and homocitrullinuria are the characteristic features of the hyperammonemia, hyperornithinemia, and homocitrullinuria (HHH) syndrome caused by a defect in the ornithine transporter (ORNT-1). 

Citrulline is exchanged for ornithine across the inner mitochondrial membrane by ORNT-1. Ornithine is produced in the cytosol as the final step in the urea cycle and must be returned to the mitochondrial matrix for transcarbamoyla-tion by OTC. A second ornithine-citrulline antiporter (ORNT-2) is also expressed in the liver mitochondria and may attenuate the severity of disease in patients with HHH (Hyperammonemia, Hyperornithinemia, Homocitrullinuria) disease due to ORNT-1 deficiency. This disorder typically manifests later in life with intermittent hyperammonemic encephalopathy and protein aversion. Intramitochondrial ornithine deficiency causes both hyperammonemia and hyperornithinemia due to a lack of substrate for OTC. Homocitrullinuria occurs due to the use of lysine by OTC as an alternate substrate. The diagnosis is confirmed by mutation analysis. 

Thus there are two major differences in the two types of hyperornithinemia. The first is the high level of blood ammonia accompanied by the severe clinical manifestations of hyperammonia. The second is the much higher level of ornithinemia, 12-14 mg/100 ml compared with less than 2 mg/100 ml. It seems likely that the blood level of ornithine... 

Shih, V. E., Efron, M. L., and Moser, H. W., Hyperornithinemia and homo-citrullinuria with ammonia intoxication, myoclonic seizures and mental retardation. Amer. J. Bis. Child. 117, 83-92 (1969). 

A (UsorAex hyperornithinemia of the retina and choroid with gyrate atrophy and progressive degeneration is due to the deficiency of the enzyme omithine-5-aminotransferase (OAT). OAT deficiency is inherited as an autosomal recessive disorder and illustrates the metabolic importance of ornithine, a nonprotein amino acid (Chapter 17). Ornithine participates either as a substrate or a product of five enzymatic reactions. Two biochemical mechanisms have been proposed to explain the pathophysiology of gyrate atrophy of the choroid and the retina. One is that a high ornithine concentration causes reduced formation of... 

Hyperornithinemia- Defect in mitochondrial hyperammonemia- transport of ornithine homocitrulhnuiia (HHH syndrome) Disorders of carbohydrate metabolism Hyperornithinemia, hyperammonemia, homocitrullinuria, hyperglutaminemia, hyperalaninemia Ataxia, lethargy, vomiting, choreoathetosis, seizures, coma, developmental delay Protein restriction arginine supplementation None... 

Shih V E. (1973) Laboratory Techniques for the Detection of Hereditary Metabolic Disorders CRC, Boca Raton, Florida Sipila I., Simell O., and O Donnell J. ] (1981) Gyrate atrophy of the choroid and retina with hyperornithinemia Characterization of mutant liver L-ornithine 2-oxoacid aminotransferase kinetics / Chn. Invest. 67, 1805-1807... 

Hyperornithinemia - hyperammonemia - homocitrullinuria Hyperi n sul inis m-hy p eram mo nemi a (H IMA)... 

With the exception of glutaric aciduria type I and hyperornithinemia there is no or a very doubtful causal relationship between the biochemical abnormality and the symptoms of psychomotor/neurological impairment. 

Fig. 12.1. Position of ornithine in the urea cycle and in biosynthetic pathways for proline, polyamines and creatine. 12.1, defect in hyperornithinemia i, ornithine-5-amino-transferase (mitochondrial) 2, ornithine transcarbamylase (mitochondrial) 3, arginase (cytosolic) 4, glycine transaminidase 5, ornithine decarboxylase (cytosolic) 6, guanidi-noacetate methyltransferase (cytosolic)...

Table 12.1. Ornithine-6-aminotransferase deficiency (hyperornithinemia) (more than...

Loading tests are unnecessary in the diagnosis of hyperornithinemia, the hyperlysinemias, 2-amino-/2-oxoadipic aciduria and hydroxylysinuria provided careful analysis of metabolites is performed. 

Gyrate atrophy of choroid and retina without hyperornithinemia (autosomal recessive)... 

Fig. 12.3. Diagnostic policy for hyperornithinemia (HOGA) starting points are clinical symptoms and/or the finding of hyperornithinemiaZ-ornithinuria. Findings compatible with defect in creatine synthesis DD, differential diagnosis...

Valtonen, M., Nanto-Salonen, K., Jaaskelainen, S. et al. (1999) Central nervous system involvement in gyrate atrophy of the choroid and retina with hyperornithinemia, /. Inker. Metab. Dis., 22, 855-866. 

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