Primary Pyruvate Dehydrogenase Complex Deficiency Mimicking Cytomegalovirus Foetopathy on Prenatal Brain Imaging: A...

We report a case of primary pyruvate dehydrogenase complex deficiency (PPDCD) presenting with prenatal neuroimaging features highly suggestive of cytomegalovirus (CMV) fetopathy, highlighting an important alternative diagnosis when infectious investigations are negative.

A 32-year-old patient was referred at 29 weeks' gestation for fetal microcephaly, borderline ventriculomegaly, and a short corpus callosum. Detailed neurosonography and fetal MRI demonstrated a clastic pattern including a periventricular echogenic halo, germinolysis pseudocysts, delayed sylvian operculation, and reduced transverse cerebellar diameter - findings classically associated with congenital CMV infection. Despite this highly suggestive imaging phenotype, extensive infectious work-up was negative. Given the severity of cerebral lesions, pregnancy termination was elected. Neuropathological examination confirmed clastic lesions and showed inferior olivary nuclei heterotopia, dentato-olivary dysplasia, thalamic microcalcifications, and hypoplastic pyramidal tracts. This distinctive combination raised suspicion of a metabolic disorder affecting cerebral energy metabolism. Subsequent exome sequencing identified a de novo pathogenic duplication in the PDHA1 gene, confirming the diagnosis of PPDCD.

This case demonstrates that PPDCD can closely mimic CMV fetopathy on prenatal brain imaging that one should evocate in case of such an imaging pattern and negative infectious testing. Its recognition has major implications for counseling and recurrence risk assessment.