A rare inborn error of metabolism associated with a Dandy–Walker malformation

Abstract

A baby girl, born to second-degree consanguineously married couple, was delivered by forceps, after a full-term pregnancy. Apgar scores were 9 and 10, birth weight 4,100 g, and head circumference 35 cm. The baby was hospitalized, at the age of 20 days, for recurrent myoclonic seizures. Physical examination found hypotonia and absent reflexes. Amino acid analysis of the cerebrospinal fluid (CSF) and plasma was performed, to exclude the possibility of metabolic disorder. A brain ultrasonography found hypoplastic corpus callosum. An expansion of the cisterna magna communicating with the fourth ventricle and a cerebellar vermis hypoplasia were also showed. These findings, suggested a Dandy–Walker malformation. 1 day later, brain magnetic resonance (MR) imaging and spectroscopy were performed. MRI confirmed the brain ultrasonography findings (Fig. 1). On the T1and T2-weighted images, the appearance of the white matter myelination was inappropriate for age. The axial T2-weighted images revealed increased signal intensity in the dorsal brain stem, the middle cerebellar peduncles, and the posterior limbs of the internal capsules. Diffusion-weighted MR images found hyperintense signal intensity in these areas, in combination with low apparent diffusion coefficient (ADC) values, consistent with restricted diffusion (Fig. 2). Localized proton MR spectroscopy showed a markedly increased peak intensity at 3.55 ppm, which was assigned to glycine and a lactate peak at 1.33 ppm (Fig. 3). The diagnosis of nonketotic hyperglycinemia (NKH) was made by laboratory findings of elevated CSF and plasma glycine levels, which were 250 lmol/L (normal range 1–15 lmol/L) and 1,540 lmol/L (normal range 230–740 lmol/L), respectively. The CSF-to-plasma glycine ratio was also elevated to 0.16 (normal range 0.02–0.03). 4 days later, the baby became lethargic, and the shallow respiration which began at that point progressed to intermittent apnea, requiring mechanical ventilation. 1 day later the infant died.