Nonketotic hyperglycinemia (NKH) is an inborn error of glycine metabolism with autosomal recessive inheritance. Based on the age at presentation and clinical course it is classified as neonatal, infantile, late onset and transient types. Neonatal NKH is a severe and frequently lethal neurological disease. We report a neonate with a very severe form of NKH, who was symptomatic at birth and did not respond to sodium benzoate and dextromethorphan therapy.

» Case Report

A male baby was born at 36 wk of gestation to a healthy,consanguineous, Indian, Hindu couple by emergency cesarean section done because of fetal distress and severe oligohydramnios. The mother had been hospitalized in the last trimester for decreased fetal movements and had been supplemented with intravenous and oral amino acids for oligohydramnios. Previously the couple had had one full term intrauterine male fetal death, no medical records of which were available.

The baby cried immediately after birth but started convulsing within a few minutes thereafter. The convulsions were myoclonic in nature occurring at 30-45 seconds intervals. The baby's birth weight was 2.3 Kg, length 48 cm and head circumference 33 cm. The baby had natal teeth and was severely hypotonic. There were no congenital anomalies. The seizures were refractory to intravenous phenobarbitone, phenytoin and pyridoxine injections and subsided only with a high dose midazolam infusion. The baby was put on ventilatory support.

On investigation the hemogram, serum calcium, blood sugar, liver function tests, blood urea nitrogen, serum creatinine and electrolytes were normal. Serum lactate was 2 mmol/L (Normal:0.7-2.1 mmol/L). There was no ketonuria. Arterial blood gas analysis showed metabolic acidosis (PH: 7.154, PCO2: 30.3, PO2: 123.4, HCO3: 10.4). On the second day of life serum ammonia was 210 ??gm/ L (normal 15-90 ??gm/liter) but decreased to 30 ??gm/ L after two days. Cranial ultrasonography showed bilateral ventricular prominence. C.T. scan could not be done because of the baby's poor general condition. Urine chromatogram for organic urinary compounds showed excessive excretion of glycine but no organic acids. A diagnosis of hyperglycinuria was made. Sodium benzoate (500 mg/Kg/day) and dextromethorphan (3.5 mg/Kg/day) were started, but his seizures remained uncontrolled. The baby succumbed on the 14th day of life. CSF and blood samples showed plasma glycine levels of 944 mmoles/L (normal 232-745 ??moles/L) and CSF glycine was 356 ??moles/L (normal 2.3-14.2 ??moles/L). The CSF/plasma glycine ratio was 0.38 (greater than 0.08 is diagnostic of hyperglycinemia).

» Discussion

NKH is a rare inborn error of glycine metabolism with an incidence of 1 in 200,000.

Deficient activity of GCS leads to accumulation of large quantities of glycine in the CNS. This allosterically activates N -methyl-D-aspartate (NMDA) receptors, located in the hippocampus, cerebral cortex, olfactory bulb and cerebellum to produce excitoneurtoxicity leading to intractable seizures.