Atypical and variable clinical presentation of glutaric aciduria type I.

We report atypical and variable clinical presentation of glutaric aciduria type I (GA I) in four children from two Greek families. In one family, a boy with typical biochemical and neuroradiological features of GA I suffered a metabolic crisis at 16 months of age resulting in a severe movement disorder. His sister, two years older and showing identical biochemical features, has remained neurologically normal throughout childhood and at six years of age is attending normal primary school. Both children are homozygous for P217 L, a novel mis-sense mutation in exon 7 of the glutaryl-CoA dehydrogenase (GCDH) gene. In the other family, monozygotic twins presented at 6 years of age with mild developmental delay and a single episode of hypoglycaemia. Cranial magnetic resonance imaging (MRI) scans in both twins revealed almost identical high-signal alterations in the periventricular white matter and in the centrum semiovale. Biochemical analyses showed massive urinary excretion of glutaric and 3-hydroxyglutaric acids and carnitine depletion. Molecular studies showed compound heterozygosity for two novel putative null mutations, IVS6-1 G > A and Y413 X, in the GCDH gene. The milder clinical course of GA I in three of the four Greek patients demonstrates the phenotypic heterogeneity of the disease even within families. Asymptomatic siblings of GA I patients should always be investigated, and molecular studies may be useful for confirming the diagnosis, particularly when the presentation is atypical.

Benign congenital hemifacial spasm.

Hemifacial spasm (HFS) is characterized by involuntary, irregular contraction of the muscles innervated by one facial nerve. Usually, it is caused by facial nerve injury either due to microvascular compression or a posterior fossa tumor, but it also occurs without apparent cause. It is rare in children; no congenital cases have yet been reported. We report the first case of congenital HFS in a term newborn delivered by forceps after a normal labor. Multimodal evoked potentials, electroencephalogram, computed tomography of the petrous bone, as well as brain magnetic resonance imaging and angiography disclosed no abnormalities. Serial neurodevelopmental examinations and video recordings performed until 8 months of age documented a normal neurodevelopmental status and a tendency for spontaneous diminution of the HFS. An intrauterine facial nerve injury as the causative factor of HFS, being responsible for its benign course, is proposed.