From Severe Neonatal Encephalopathy to Slowly Neurologic Progressive Disease: Pyruvate Dehydrogenase Deficiency Related to PDHA1 Variants.
Sofia Corbaz, Daniela Alejandra Pibernus, Mariana Amina Loos et al.
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Case in brief
Four Argentine children with PDHA1-related pyruvate dehydrogenase complex deficiency had presentations spanning severe neonatal encephalopathy with central apneas to slowly progressive neurologic disease in childhood. All had lactic acidosis and structural brain abnormalities; three met criteria for Leigh syndrome. Molecular testing found four missense variants in conserved regions of the E1α subunit, including the novel c.260T>C p.(Ile87Thr) variant. All received thiamine and a ketogenic diet, with favorable reported outcomes in seizure control, neurodevelopment, and metabolic stability.
What made this case unusual
The clinical range extended from severe neonatal disease to a slowly progressive childhood course. The report also described a previously undescribed radiologic pattern in one patient and a novel PDHA1 missense variant whose modeled structure suggested impaired thiamine pyrophosphate binding.
Diagnostic / clinical pearl
In children with lactic acidosis and structural brain abnormalities, PDHA1-related pyruvate dehydrogenase complex deficiency can present with markedly different neurologic courses; molecular testing can help establish the diagnosis.