MRI findings in neonatal nonketotic hyperglycinemia

Christopher J. Butler, Marcus Likeman and Andrew A. Mallick. Distinctive Magnetic Resonance Imaging Findings in Neonatal Nonketotic Hyperglycinemia.  Pediatric Neurology.  In press.

This term neonate was born by normal vaginal delivery following an uneventful pregnancy. No resuscitation was required. A few hours after birth, he required invasive ventilation because of a decreasing conscious level, generalized hypotonia, and a reduced respiratory drive. There were no dysmorphic features except bilateral talipes equinovarus. After extubation, he had antigravity movements in all limbs and preservation of deep tendon reflexes. He appeared jittery and demonstrated an exaggerated startle reflex to external stimuli.

Cranial magnetic resonance imaging performed on day ten of life showed symmetrical high intensity of the corticospinal tracts, central tegmental tracts, and internal capsule. The posterior fossa cerebrospinal fluid space was enlarged in keeping with a mega cisterna magna. A comprehensive metabolic screen later identified increased plasma and cerebrospinal fluid glycine levels. GLDC gene analysis showed that the child was compound heterozygous with a GLDC exon 1-4 deletion and a missense mutation consistent with a diagnosis of nonketotic hyperglycinaemia (NKH).

T2-weighted axial magnetic resonance (A) and diffusion-weighted (B) images show high intensity of central tegmental and corticospinal tracts.

Discussion

NKH is a rare autosomal recessive neurometabolic disorder resulting in excessive accumulation of glycine.  This child had a classical presentation of neonatal NKH; however, diagnosis can be problematic with nonspecific presentations. Widespread spongiosis of the myelinating ascending and descending white matter tracts is the main histopathological feature of neonatal NKH.  This child exhibited increased white matter signal intensity on T2-weighted and diffusion-weighted images in the classical anatomical locations of spongiosis. Neuroimaging may be available before the results of many biochemical investigations in a sick neonate, and this pattern of white matter change should alert readers to a possible diagnosis of NKH.