TY - JOUR
T1 - A neonate with ornithine aminotransferase deficiency; insights on the hyperammonemia-associated biochemical phenotype of gyrate atrophy
AU - Kaczmarczyk, Aneta
AU - Baker, Mark
AU - Diddle, Julianna
AU - Yuzyuk, Tatiana
AU - Valle, David
AU - Lindstrom, Kristin
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/6
Y1 - 2022/6
N2 - Gyrate atrophy of the choroid and retina (GACR) secondary to deficiency of ornithine aminotransferase (OAT) is a rare autosomal recessive metabolic disorder usually diagnosed in childhood when patients develop myopia and a characteristic retinal degeneration accompanied by hyperornithinemia. Plasma ammonia is normal or sub-normal after the neonatal period. A few GACR patients present in early infancy with hyperammonemia, encephalopathy and a biochemical profile of low plasma ornithine, citrulline and arginine, with increased urinary excretion of homocitrulline and orotic acid, resembling a primary urea cycle disorder. In these patients, ornithine levels do not increase until late infancy or following arginine or citrulline supplementation. We describe a patient with OAT deficiency who presented in the first month of life with episodes of lethargy, vomiting, and hypothermia. He had two episodes of hyperammonemia associated with subnormal levels of plasma ornithine, citrulline and arginine as well as elevated urinary excretion of homocitrulline and orotic acid. Unlike previously reported cases, intermittent hyperornithinemia was observed prior to the first hyperammonemic episode and citrulline supplementation. The latter alleviated the symptoms, normalized ammonia level, and led to increased plasma ornithine concentration. Furthermore, despite a protein restricted diet and ammonia scavenger treatment, continued supplemental citrulline was necessary to prevent hyperammonemia. Molecular analysis confirmed OAT deficiency, differentiating it from proximal urea cycle disorders and deficiency of the mitochondrial ornithine transporter, ORC1, (Hyperammonemia-Hyperornithinemia-Homocitrullinuria syndrome). Synopsis: Hyperornithinemia alternating with hypoornithinemia and hyperammonemia in a neonatal-onset case of gyrate atrophy with ornithine aminotransferase deficiency.
AB - Gyrate atrophy of the choroid and retina (GACR) secondary to deficiency of ornithine aminotransferase (OAT) is a rare autosomal recessive metabolic disorder usually diagnosed in childhood when patients develop myopia and a characteristic retinal degeneration accompanied by hyperornithinemia. Plasma ammonia is normal or sub-normal after the neonatal period. A few GACR patients present in early infancy with hyperammonemia, encephalopathy and a biochemical profile of low plasma ornithine, citrulline and arginine, with increased urinary excretion of homocitrulline and orotic acid, resembling a primary urea cycle disorder. In these patients, ornithine levels do not increase until late infancy or following arginine or citrulline supplementation. We describe a patient with OAT deficiency who presented in the first month of life with episodes of lethargy, vomiting, and hypothermia. He had two episodes of hyperammonemia associated with subnormal levels of plasma ornithine, citrulline and arginine as well as elevated urinary excretion of homocitrulline and orotic acid. Unlike previously reported cases, intermittent hyperornithinemia was observed prior to the first hyperammonemic episode and citrulline supplementation. The latter alleviated the symptoms, normalized ammonia level, and led to increased plasma ornithine concentration. Furthermore, despite a protein restricted diet and ammonia scavenger treatment, continued supplemental citrulline was necessary to prevent hyperammonemia. Molecular analysis confirmed OAT deficiency, differentiating it from proximal urea cycle disorders and deficiency of the mitochondrial ornithine transporter, ORC1, (Hyperammonemia-Hyperornithinemia-Homocitrullinuria syndrome). Synopsis: Hyperornithinemia alternating with hypoornithinemia and hyperammonemia in a neonatal-onset case of gyrate atrophy with ornithine aminotransferase deficiency.
KW - Citrulline supplementation
KW - Gyrate atrophy of the choroid and retina
KW - Hyperornithinemia
KW - Neonatal hyperammonemia
KW - Ornithine aminotransferase deficiency
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U2 - 10.1016/j.ymgmr.2022.100857
DO - 10.1016/j.ymgmr.2022.100857
M3 - Article
C2 - 35782604
AN - SCOPUS:85126527789
SN - 2214-4269
VL - 31
JO - Molecular Genetics and Metabolism Reports
JF - Molecular Genetics and Metabolism Reports
M1 - 100857
ER -