Arginase I deficiency: Severe infantile presentation with hyperammonemia: More common than reported?

作者：Jain Ghai Shailly; Nagamani Sandesh C Sreenath; Blaser Susan; Siriwardena Komudi; Feigenbaum Annette^*

来源：Molecular Genetics and Metabolism, 2011, 104(1-2): 107-111.

DOI：10.1016/j.ymgme.2011.06.025

• Arginase deficiency
• Hyperammonemia
• Hyperargininemia
• Orotic acid
• Guanidino compounds

Enzyme defects of the urea cycle typically present with significant hyperammonemia and its associated toxicity, in the first few months of life. However, arginase 1 (ARG1) deficiency, a rare autosomal recessive disorder, has classically been the exception. ARG1 deficiency usually presents later in life with spasticity, seizures, failure to thrive and developmental regression. Neonatal and early infantile presentation of ARG1 deficiency with severe hyperammonemia remains rare and only six such cases have been described. We report a severely affected infant with ARG1 deficiency who presented at 6 weeks of age with lethargy, poor feeding and severe encephalopathy caused by hyperammonemia. The clinical and biochemical features of the proband and six other previously reported cases with neonatal or infantile-onset presentation of ARG1 deficiency with hyperammonemia are reviewed. In addition, the clinical spectrum of seven previously unpublished patients with later onset ARG1 deficiency, who also experienced recurrent hyperammonemia, is presented.
Several biochemical abnormalities have been postulated to play a role in the pathogenesis of the neurological changes in ARG1 deficiency including hyperargininemia, elevated guanidino compounds and elevated glutamine levels, as well as the hyperammonemia. The index case demonstrated many of these. The cases reviewed here suggest a genotype/phenotype correlation and advocate for the addition of arginine as a primary target in newborn screening programs.

• 出版日期2011-10