Case Report: When metabolism meets malabsorption: Imerslund-Gräsbeck syndrome with coexisting propionic acidemia...

Propionic acidemia and Imerslund-Gräsbeck syndrome are rare inherited metabolic disorders with distinct pathophysiological mechanisms. Their occurrence in the same child is extremely unusual and can create diagnostic and therapeutic challenges because of overlapping neurological and hematological manifestations.

A 1.5-year-old boy presented with recurrent episodes of encephalopathy precipitated by febrile illnesses, associated with vomiting, severe metabolic acidosis, ketosis, and refractory focal status epilepticus. Following repeated metabolic crises, developmental stagnation became evident. On examination, he was encephalopathic with right-sided weakness, hypotonia, and brisk deep tendon reflexes. Investigations revealed high anion gap metabolic acidosis, mild hyperammonemia, neutropenia, microcytic anemia, and persistent proteinuria. Metabolic workup showed elevated propionyl carnitine with increased urinary 3-hydroxypropionic acid and propionyl glycine, suggestive of propionic acidemia. Whole-exome sequencing identified a homozygous pathogenic variant in the PCCB gene, confirming propionic acidemia, along with a novel homozygous stop-gain variant in the CUBN gene consistent with Imerslund-Gräsbeck syndrome. Neuroimaging demonstrated bilateral basal ganglia involvement, diffuse white matter abnormalities, and progressive cerebral atrophy, reflecting recurrent metabolic injury. The child was treated with anti-seizure medications, metabolic stabilization, protein-restricted diet, mitochondrial cocktail supplementation, and monthly vitamin B12 therapy.

This case represents an exceptionally rare coexistence of propionic acidemia and Imerslund-Gräsbeck syndrome. It highlights the importance of considering dual pathology in children with atypical clinical or biochemical features and underscores the value of comprehensive genetic evaluation in complex neurometabolic disorders.