Methylmalonic acidemia with recurrent hemophagocytic lymphohistiocytosis: a case report and review of the literature.

BACKGROUND

Methylmalonic acidemia is a rare autosomal recessive disorder of propionate catabolism characterized by the accumulation of propionic acid and methylmalonic acid caused by methylmalonyl-CoA mutase deficiency. Clinical presentations range from acute deterioration in the neonatal period to later onset with a heterogeneous clinical course. Metabolite accumulation results in systemic involvement, affecting the nervous, gastrointestinal, and renal system functions and causing cardiomyopathy. Bone marrow dysfunction manifesting as neutropenia and anemia is a common hematological finding. Although rare, three cases of secondary hemophagocytosis were documented.

CASE PRESENTATION

An 18-year-old male patient diagnosed with methylmalonic acidemia presented with vomiting and altered mental status. He had a medical history of presumably hemophagocytic lymphohistiocytosis (HLH) at the age of 17 months. Physical examination, laboratory tests, and bone marrow aspiration results met the HLH-2004 diagnostic criteria, confirming a recurrent HLH. Although he recovered after intensive treatment, his cognitive function declined. Retrospective analysis revealed higher serum levels of ferritin during acute decompensations compared with nonattack periods. Correlation analysis revealed a strong relationship between serum ferritin and propionylcarnitine, one of the major propionyl-CoA-derived metabolites.

CONCLUSIONS

HLH is a rare and underrecognized hematologic emergency in methylmalonic acidemia, and its early diagnosis and treatment are critical. Serum ferritin may be a useful clinical biomarker in the diagnosis of HLH-associated attacks in methylmalonic acidemia.

© 2025. The Author(s).