MRI Features of 4 Female Patients With Pyruvate Dehydrogenase E1 alpha Deficiency

Abstract

Pyruvate dehydrogenase complex is a key intramitochondrial multienzyme complex required for the conversion of pyruvate to acetyl-CoA. The majority of patients with pyruvate dehydrogenase deficiency have a defect in the E1 alpha subunit, associated with mutations in the PDHA1 gene. In this report, we submit detailed magnetic resonance images in four affected female patients with PDHA1 mutations, who present with severe cortical atrophy, dilated ventricles, and an incomplete corpus callosum. In one of these patients, the MRI pattern prompted molecular diagnostic testing when enzymatic testing was normal. We underscore that this constellation of features, which may be misdiagnosed as periventricular leukomalacia, illustrate a pattern highly suggestive of a deficiency of pyruvate dehydrogenase E1 alpha in female patients and should trigger appropriate diagnostic investigations.

Novel imaging findings in pyruvate dehydrogenase complex (PDHc) deficiency—Results from a nationwide population‐based study

“…It is therefore important to consider PDHc deficiency in the differential diagnosis of cerebral palsy in girls with atypical perinatal history. In contrast to a previous case report that emphasized the asymmetry of ventricular dilatation in PDHc deficiency as a distinguishing pattern, 11 half of the patients in our study had symmetric ventricular dilatation.…”

“…The reason for this difference could be explained by the fact that in affected males, severe PDHA1 mutations that essentially abrogate enzyme activity in the cells are thought to be embryonically lethal and only affected male fetuses with milder mutations, and significant residual enzyme activity is believed to survive until birth 13,32 . Consequently, newborn boys with PDHA1 deficiency typically do not manifest severe structural brain anomalies at birth 11 although this has been described occasionally 32 (and was found in one of our patients). In female patients, random X inactivation leads to expression of either the mutant or normal allele in neuronal cells.…”

The aetiology of neonatal seizures and the diagnostic contribution of neonatal cerebral magnetic resonance imaging

“…In general, the findings in our study were comparable to the findings in other studies . 1 H‐MRS is particularly useful in this group of infants.…”

Pyruvate dehydrogenase deficiency and the brain

“…In the case report by Sharma et al., an MRI at 5 months of age in a patient with developmental delay and hypotonia revealed dilatation of the right lateral ventricle with leukomalacia and subependymal cysts, while the left side of the brain appeared normal. While asymmetric ventriculomegaly and subependymal cysts have been described previously in patients with PDH deficiency, 6 the extreme degree of asymmetry and the absence of any other radiological abnormality is particularly striking in this case. In the case report by Giribaldi et al., episodes of gait ataxia and muscle weakness developed in association with infections.…”