Background Inherited hyperammonemia is a challenging disorder to diagnose. Various enzymes can be mutated in the urea cycle, but NAGSD is the rarest one. In this case series, we report 2 siblings with a neurometabolic disorder and their neuroimaging findings and genome sequencing, which led to the discovery of a new variation in the related gene. Case Series A 16-year-old girl presented to the emergency department with a focal seizure, right paresis, and a Glasgow Coma Scale score of 9. Imaging of the brain indicated abnormalities in the dentate nucleus and parietal lobes. Severe malnutrition with high serum ammonia suggested an inherited urea cycle deficiency. A month later, her 7-year-old brother presented to the emergency department with fatigue, headaches, and neurodevelopmental regression. He was initially suspected of encephalitis or metabolic disorders, but he also had high serum ammonia and plasma glutamic acid. Whole exome sequencing indicated a variant of uncertain significance linked to NAGSD. Sanger sequencing confirmed an autosomal recessive pattern (c.791C>T, p.Thr264Met) in both siblings, with parents identified as heterozygote carriers. Discussion Although most of the presentations in NAGSD happen early in life, both of our cases presented their neurologic presentations later than the usual reported age range. Previous investigation on this specific type of variation showed that NAGS activity is enough to live an everyday life, and the key problem is in the solubility of the enzyme, which has been decreased in the corresponding variation and can present later in life.
Kooshki et al. (Sat,) studied this question.
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