Pyruvate dehydrogenase-e1α deficiency presenting as recurrent demyelination: an unusual presentation and a novel mutation

Abstract

The nucleus-encoded mitochondrial pyruvate dehydrogenase enzyme complex plays key roles in cellular energy metabolism and acid-base equilibrium. Pyruvate dehydrogenase complex deficiency is due to loss-of-function mutation in one of the five component enzymes, most commonly E1α-subunit. The common clinical presentation ranges from fatal infantile lactic acidosis in newborns to chronic neurological dysfunction. We describe here an unusual presentation of E1α-subunit deficiency presenting as recurrent demyelination, Guillain-Barré syndrome-like demyelinating polyneuropathy at the onset, and ophthalmoplegia in a young infant. The clinical phenotype of the mutation in the patient was unique as compared to the previous reported cases of pyruvate dehydrogenase deficiency. The mother was found to be a mosaic carrier of the mutation. This phenotypic variability of pyruvate dehydrogenase complex deficiency and early suspicion of its unusual neurological manifestations is highlighted. Thiamine and ketogenic diet can be helpful.

Fig. 1

(a and b): MRI brain (FLAIR and T2) at the age of 15 months (second deterioration) shows hyperintense signal involving bilateral hilum of dentate nucleus, superior and middle cerebellar peduncles, and periventricular white matter suggestive of demyelination. These areas were hypo- to isointense on T1 images and showed no restriction on diffusion weighted or any enhancement post-contrast. Rest of the supratentorial brain parenchyma is normal in signal intensity and gray-white matter differentiation. Bilateral basal ganglia, thalami, and corpus callosum are normal. (c and d): MRI brain (FLAIR and T2) at the age of 18 months (first presentation to us) shows subtle T2/FLAIR hyperintensities in bilateral periventricular parietooccipital white matter. These showed no evidence of diffusion restriction or post-contrast enhancement. Bilateral basal ganglia, thalami, and corpus callosum are normal. (e and f): MRI brain (FLAIR and T2) at the age of 22 months (follow-up at 1 year after the illness) shows bilateral symmetrical linear areas of gliotic change in bilateral periventricular white matter, centrum semiovale, and globus pallidi. No diffusion restriction was seen. Corpus callosum is thinned out in body portion. Ventricular system is dilated with dilated 3rd and 4th ventricles. Bilateral thalami appear normal