ESPE Abstracts

Background and Aims: Combined malonic and methylmalonic aciduria (CMAMMA) is a rare genetic disorder that affects the body's ability to break down certain proteins and fats. It is caused by mutations in the ACSF3 gene, which provides instructions for making an enzyme involved in the metabolism of fatty acids. As a result of the enzyme deficiency, individuals with CMAMMA experience an accumulation of malonic and methylmalonic acids in their blood and urine.

Case: At 2 days old, a baby born at 36+5 weeks with a weight of 2.02kg was brought to the emergency room due to apnea. Initial laboratory testing revealed an elevated C-reactive protein level of 2.31 mg/dL (reference range, 0-0.3 mg/dL) and cerebrospinal fluid analysis showed an increased white blood cell count of 48 cells/mm³, raising concern for meningitis. Despite negative culture results for viral and bacterial pathogens, the infant was treated with antibiotics and discharged without complications. At approximately 1 month of age, the infant presented with a fever of 38.2°C and physical examination revealed a left inguinal mass, ultimately diagnosed as necrotizing lymphadenitis after imaging studies. The infant underwent incision and drainage by a surgeon, and cultures were positive for methicillin-resistant Staphylococcus aureus. At 7 months of age, the infant was readmitted for a 1-2cm abscess in the perianal region that spontaneously drained during hospitalization and was treated with intravenous antibiotics.

Result: The infant underwent immunological tests including lymphocyte subset analysis and primary immunodeficiency next-generation sequencing panel analysis, which revealed the presence of the ACSF3, c.[689G>A];[1240-3C>G](p.[Trp230Ter];[?]). These findings led to a diagnosis of CMAMMA, which was confirmed to be inherited from both parents through family testing. Although newborn screening via dried blood spot was negative for this condition, metabolic disease testing was initiated following diagnosis. Serum amino acid testing did not reveal any significant findings, but urine organic acid testing demonstrated elevated levels of malonic acid (MA) at 49.2 (reference range, < 0 mmol/mol of creatinine) and methylmalonic acid (MMA) levels at 332.1 (reference range, <32.9 mmol/mol of creatinine), resulting in an MMA/MA ratio of 6.75.

Conclusion: The infant has been doing well without any significant complications following the diagnosis, despite experiencing more frequent cold symptoms. It is believed that the patient has a high likelihood of having a benign course. This is the first reported case of an ACSF3 mutation in Korea.