In propionic aciduria and methylmalonic aciduria, hyperammonemia as a symptom of metabolic decompensation is one of the major clinical problems. Hyperammonemia is a true neonatal emergency with high mortality and neurological complications in most survivors. It requires a rapid and vigorous treatment in order to normalize the ammonia concentration as fast as possible. We report on two full-term neonates, one with propionic aciduria and the other with methylmalonic aciduria, whose plasma ammonia concentrations responded dramatically to oral N-carbamylglutamate. N-carbamylglutamate, added to the classic treatment, quickly normalized plasma ammonia levels in both patients and avoided the need of hemodialysis or peritoneal dialysis. A particularly sudden fall of ammonia was obtained in one patient through beginning N-carbamylglutamate treatment precociously.

Hyperammonemia is a true neonatal emergency with high toxicity for the central nervous system and developmental delay. The causes of neonatal hyperammonemia are genetic defects of urea cycle enzymes, organic acidemias, lysinuric protein intolerance, hyperammonemia–hyperornithinemia– homocitrullinemia syndrome, transient hyperammonemia of the newborn, and congenital hyperinsulinism with hyperammonemia. In some of these conditions the high blood ammonia levels are due to the reduction of N-acetylglutamate, an essential cofactor necessary for the function of the urea cycle, or to the reduction of carbamoyl-phosphate synthase-I activity. In these cases, N-carbamylglutamate (carglumic acid) can be administered together with the conventional therapy. Carglumic acid is an analog of N-acetylglutamate that has a direct action on carbamoyl-phosphate synthase-I. Its effects are reactivation of the urea cycle and reduction of plasma ammonia levels. As a consequence it improves the traditional treatment, avoiding the need of hemodialysis and peritoneal dialysis. In this review we evaluate the possible field of application of carglumic acid and its effectiveness and safety.

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We report an infant with neonatal nonketotic hyperglycinemia (NKH), diagnosed early and treated with dextromethorphan (DM) and sodium benzoate therapy from the 65th hour of life. Initially the patient responded to treatment showing clinical and electroencephalographic improvement: myoclonic jerks disappeared, muscular tone, reactivity to stimuli and spontaneous movements increased, assisted ventilation was no longer necessary and bottle feeding was initiated successfully; on EEG the suppression-burst pattern disappeared and the background activity was well-organized. At three months of age he developed flexor spasms and hypsarrhythmia. In spite of increasing doses of DM as high as 40 mg/kg/day and persistent therapy with sodium benzoate the child progressively deteriorated and died at the age of 5 months and 7 days. We stress that the adverse clinical course occurred in our patient even though DM and sodium benzoate therapy was started much earlier than in other reported cases. It is possible that prenatal brain damage and probable genetic variants (i.e. absent or minimal residual enzymatic activity and interindividual variations in DM metabolism) affect the response to therapy.

An association between the deletion of chromosome 22q11.2, microgastria, and impaired mucociliary function has never been observed before. A casual association seems highly unlikely and we can not exclude the possibility of genetic mechanisms that may link those syndromes.