Non-ketotic hyperglycinemia as a cause for respiratory failure in a newborn

Background: Non-ketotic hyperhyperglycinemia with manifestation in the neonatal period constitutes a severe inborn error of metabolism with a very poor prognosis. Methods: Case report Patient: The female baby was born to a GII, PI mother (unrelated parents) after an uneventful pregnancy with normal fetal movements (birth weight: 3510 gr) at 38 weeks of gestation. APGAR scores were 9 and 10at 5 and 10 minutes respectively. Mean blood pressure, heart rate, respiratory rate and core body temperature were normal. On day two of life the newborn had a poor suck and developed progressive lethargy. On physical examination generalized muscular hypotonia, absent deep tendon reflexes, extreme sleepiness, and insufficient respiratory drive were noted, which required mechanical ventilation. Serum chemistry, blood glucose, serum lactate and ammonia, and full blood count were normal. The recording of an amplitude-integrated EEG showed continuous burst suppression pattern despite administration of phenobarbitone and vitamin B 6. This finding was confirmed by conventional EEG recording (Figure 2). However, the neonate did not have manifest seizures. Further diagnostic work-up in our neonate for inborn errors of metabolism yielded the diagnosis of non-ketotic hyperglycinemia (glycine in CSF: 360.1µmol/l, reference value: 5.9–8.5µmol/l; plasma glycine: 2196µmol/l; reference value: 224–514µmol/l). After counseling the parents about the extreme poor prognosis that carries non-ketotic hyperglycinemia, intensive care treatment was withheld and the newborn was given palliative care. Conclusion: Inborn errors of metabolism (non-ketotic hyperglycinemia) have to be taken into the differenzial diagnosis of the severely floppy infant with respiratory insufficiency. Elevated glycin levels may cause peripheral floppiness with concomitant cerebral hyperexcitation.

References

1. Hoover-Fong JE, Shah S, Van Hove JL, Applegarth D, Toone J, Hamosh A. Natural history of non-ketotic hyperglycinemia in 65 patients. Neurology 2004; 63:1847–1853