If it Walks like a Duck and Talks like a Bird, it Still could be a Duck

Pyruvate Dehydrogenase Complex Deficiency (PDCD) is a mitochondrial disease due to carbohydrate oxidation deficiency, decreases ATP production and energy deficit. Majority of cases are caused by pathogenic variants in the X-linked PDHA1 gene. Severe manifestations include prenatal findings of abnormal brain imaging and growth retardation with neonatal neurologic manifestations (intractable seizures, structural brain anomalies and degenerative encephalopathy), lactic acidosis and high serum Pyruvate and neonatal death. Variable expression has been described. PDHA1 mosaicism is rare and has been reported so far in eight cases, seven male and one female.

Case presentation: We report a case of a term male newborn with prenatal history of IUGR and abnormal brain imaging (corpus callosum agenesis, ventriculomegaly, cavum septum pellucidum, cystic changes).

The patient was born upon vaginal delivery, in crucial condition requiring immediate CPR. Clinical course included hemodynamic and respiratory instability, encephalopathy, seizures along with laboratory findings of elevated lactatemia with normal pyruvate -lactate ratio.

Whole Exome trio Sequencing reported a novel, De novo, deleterious variant in the PDHA1 gene: c.461C>T;p.Thr154Ile in a mosaic state (55%).
Upon diagnosis Ketogenic diet was started along with treatment of Thiamine supplement achieving immediate clinical improvement enabling to discharge at 3 months of age.

Conclusions: The combination of IUGR, abnormal brain imaging and consistently elevated lactatemia is highly suggestive of PDCD and should be suspected even in cases with non-characteristic metabolic profile due to the possibility of a mosaic state with a non-classical presentation. Early diagnosis therapeutic intervention is eminent for improving prognosis