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MRI features of 4 female patients with pyruvate dehydrogenase E1 alpha deficiency
Nicholas Ah Mew1, Johanna B Loewenstein, Nadja Kadom
1Division of Genetics and Metabolism, Children's National Medical Center, Washington, DC 20010, USA.
Insights
Pyruvate dehydrogenase E1 alpha deficiency, caused by PDHA1 mutations, presents with specific brain imaging findings in females. This pattern aids in diagnosing the condition, even with normal enzyme tests.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Pyruvate dehydrogenase complex is crucial for cellular energy metabolism.
- Deficiency often results from mutations in the PDHA1 gene, affecting the E1 alpha subunit.
- This condition impacts pyruvate to acetyl-CoA conversion within mitochondria.
Observation:
- Detailed MRI scans of 4 female patients with PDHA1 mutations were analyzed.
- Observed abnormalities included severe cortical atrophy, dilated ventricles, and incomplete corpus callosum.
- In one case, MRI findings prompted molecular testing due to normal enzymatic results.
Findings:
- A distinct pattern of brain abnormalities was identified in female patients with PDHA1 mutations.
- This neuroimaging signature is highly suggestive of pyruvate dehydrogenase E1 alpha deficiency.
- The observed MRI pattern may be misdiagnosed as periventricular leukomalacia.
Implications:
- Recognizing this MRI pattern is vital for early diagnosis in female patients.
- It highlights the importance of considering PDHA1 mutations in affected individuals.
- Prompt diagnostic investigations can be initiated based on these imaging findings.
Abstract:
Pyruvate dehydrogenase complex is a key intramitochondrial multienzyme complex required for the conversion of pyruvate to acetyl-CoA. Most 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 4 affected female patients with PDHA1 mutations who had with severe cortical atrophy, dilated ventricles, and an incomplete corpus callosum. In one of these patients, the magnetic resonance imaging pattern prompted molecular diagnostic testing when enzymatic testing was normal. We underscore that this constellation of features, which may be misdiagnosed as periventricular leukomalacia, illustrates a pattern highly suggestive of a deficiency of pyruvate dehydrogenase E1 alpha in female patients and should trigger appropriate diagnostic investigations.
