Neonatal nonketotic hyperglycinemia, attenuated phenotype

Abstract

Introduction. Nonketotic hyperglycinemia (NKH) is an autosomal recessive innate error of metabolism, whose main characteristic is the accumulation of glycine in body fluids, produced by a failure in the enzymatic cleavage complex of this amino acid. Case Presentation. We present the case of a 36-week-old newborn, with spontaneous neonatal adaptation, no history of perinatal noxa or documented hypoglycemia, who after a short period of 24 hours presented progressive neurological deterioration, rapid alteration of consciousness to coma and ventilatory failure. At admission the patient was noted for severe generalized hypotonia, hyporeflexia, absence of primitive reflexes, with episodes of isolated hiccups and abnormal eye movements. In view of the suspicion of an innate error of metabolism, an amino acid profile was performed, showing a significant elevation of glycine, 1417 umol/L (reference 94-553 umol/L). Amino acids were requested in cerebrospinal fluid, glycine very elevated 1263 umol/L (reference 3-7 umol/L), confirming the suspicion of nonketotic hyperglycinemia. It was decided to start treatment with sodium benzoate and dextromethorphan. The initial MRI was normal; in the control study, findings previously reported in the literature for this pathology were found, as well as in the electroencephalogram. Discussion. Most children with NKH will display it in the neonatal period or early infancy, with only the mildest cases presenting in late infancy or childhood. In neonatal-onset cases, 85% have severe NKH and 15% have attenuated form, as in this case. The diagnosis of NKH is made based on clinical suspicion, confirmed by laboratory findings, with the characteristic alteration of glycine in both plasma and CSF and supported by neuroimaging and electroencephalogram (EEG) findings. Conclusions. NKH is not such an unusual condition, although it is possibly underdiagnosed because of its catastrophic presentation and because it does not produce major metabolic disorders that are quickly diagnosed. For this reason, in a patient with a suggestive clinical condition, with coma, respiratory alteration and unmanageable seizures, and very characteristically hiccups, the study of amino acids in plasma, neuroimaging and EEG should be requested, in order to establish early treatment.