A new case of pyruvate dehydrogenase deficiency due to a novel mutation in the pdx1 gene

Abstract

We report a case of neonatal congenital lactic acidosis associated with pyruvate dehydrogenase E3-binding protein deficiency in a newborn girl. She had a severe encephalopathy, and magnetic resonance imaging of the brain showed large subependymal cysts and no basal ganglia lesions. She died 35 days after birth. We detected a novel homozygous deletion (620delC) in the PDX1 gene, which encodes for the E3BP subunit of the pyruvate dehydrogenase complex.

Neonatal pyruvate dehydrogenase deficiency due to a R302H mutation in the PDHA1 gene: MRI findings

“…In our term-born infant the cysts were already demonstrated at 7 days of age and, therefore, were probably congenital [3,4]. Their location in the frontal horns of the lateral ventricles, as well as in the caudothalamic grooves, was atypical for the evolution of germinal matrix haemorrhage.…”

“…Conventional MRI features of PDH deficiency have been previously described [1][2][3][4][5], and include enlarged ventricles, cerebral and cerebellar white matter involvement (including cystic change), brainstem atrophy, absence of medullary pyramids, abnormal inferior olives, cerebellar dysplasia, partial or complete agenesis of the corpus callosum, and basal ganglia hyperintensities on T2-W images. To our knowledge, this is the first report of conventional MRI and DW imaging findings in a male neonate.…”

“…Callosal malformations have been previously reported in PDH deficiency [1,4] and several other metabolic disorders, such as other mitochondrial disorders, peroxisomal biogenesis disorders, amino acid metabolism disorders and urea cycle defects [7].…”

“…Their location in the frontal horns of the lateral ventricles, as well as in the caudothalamic grooves, was atypical for the evolution of germinal matrix haemorrhage. Subependymal cysts have also been described in congenital heart disease, congenital infections and several metabolic disorders and cause primary lactic acidosis, such as Zellweger syndrome, holocarboxylase synthetase deficiency, pyruvate carboxylase deficiency, and glutaryl CoA dehydrogenase deficiency [4]. To our knowledge, only a few prior MRI observations of germinolytic cysts in termborn neonates with PDH deficiency have been reported [1,4].…”

“…Subependymal cysts have also been described in congenital heart disease, congenital infections and several metabolic disorders and cause primary lactic acidosis, such as Zellweger syndrome, holocarboxylase synthetase deficiency, pyruvate carboxylase deficiency, and glutaryl CoA dehydrogenase deficiency [4]. To our knowledge, only a few prior MRI observations of germinolytic cysts in termborn neonates with PDH deficiency have been reported [1,4]. In one of these infants, PDH deficiency was due to a rarer mutation in the PDX1 gene that encodes for the E3BP subunit of the PDH complex [4].…”