Subacute metabolic stroke in two patients with propionic acidemia with fatal and good outcome

Patients with propionic acidemia (PA) suffer from recurrent metabolic crisis presenting with metabolic acidosis and hyperammonemia. Therefor the neurological presentation with somnolence/coma mostly is related to acute metabolic decompensation. Damaging of the basal ganglia can happen during these episodes. Besides toxicity of ammonia and organic acids secundary mitochondrial dysfunction is discussed to play a role in this neurotoxicity of the basal ganglia.

Case reports: We report about two patients with PA presenting deep somnolence and severe myoclonus. Both had massive increase in urinary excretion of metabolites but no metabolic acidosis nor hyperammonemia. Both children had similar cMRI pathology with hyperintens signaling in the diffusion weighted imaging (DWI) affecting nearly the whole gray matter and generalized EEG slowing. Patient 1, a 8 year old girl died 12 hours after depicting the MRI. After developing lactate acidosis she presented non susceptible fever as well as non pulmonological hypercapnia and died within a few hours without any reaction to reanimation. She did not discharge any citrate in the urine. Patient 2, a 18 month old boy showing the same clinical and MRI presentation was found to have a CMV infection as a trigger of the metabolic decompensation. CMV was not found in CSF. He also had no urinary citrate excretion. Due to the experiences with Pat. 1 this boy was treated with citrate as well as a “mitochondrial vitamin cocktail“ and recovered completely.

Discussion: Both patients showed the clinical and MRI morphological changes of severe acute hypoxic encephalopathy without hypoxaemia. Both patients did not excrete citrate, suggesting a breakdown of energy metabolism due to secundary mitochondrial failure that mimics the clinical picture of acute hypoxic encephalopathy. Besides depletion of Krebs cycle intermediates other toxic agents like Ureidopropionate can be discussed as a specific cause.