Combined Malonic and Methylmalonic Aciduria Diagnosed by Recurrent and Severe Infections Mimicking a Primary Immunodeficiency Disease: A Case Report

Abstract

Combined malonic and methylmalonic aciduria is a rare genetic disorder caused by ACSF3 biallelic variants that results in impaired protein and fat metabolism and the accumulation of malonic and methylmalonic acids. A 52-day-old infant with a fever and a history of possible meningitis during the neonatal period was hospitalized. Multiple lesions of necrotizing lymphadenitis with abscesses in the left inguinal area were treated by incision and drainage along with appropriate antibiotic therapy, which revealed a methicillin-resistant Staphylococcus aureus infection. At 6 months of age, the patient was admitted with anal abscesses. Due to the increased suspicion of primary immunodeficiency disease, genetic testing was conducted, which revealed ACSF3 biallelic variants inherited from both parents. Urine organic acid analysis revealed elevated levels of malonic and methylmalonic acids. At 29 months, the patient showed normal growth and development without any dietary modifications. He had occasional colds, but severe bacterial infections were absent. The prognosis suggests a benign disease course. Here, we present the first reported case of ACSF3 compound heterozygote variants in Korea.

Keywords: Combined Malonic and Methylmalonic Aciduria; Methylmalonic Aciduria; Primary Immunodeficiency Disease.

Fig. 1. Computed tomography images of multiple intra-abdominal abscesses (arrows) in an infant diagnosed with combined malonic and methylmalonic aciduria. The size of the largest abscess in the left inguinal area was 26.10 mm.

Fig. 2. Patient’s family pedigree and Sanger sequencing results of the patient’s parents. The patient was found to have inherited a compound heterozygous type of mutation, receiving different mutations from each parent.