β-ureidopropionase (βUP) deficiency, caused by pathogenic variants in UPB1 , is a rare autosomal recessive disorder with fewer than 60 reported cases to date. Clinical presentation is highly variable, ranging from asymptomatic individuals to severe neurodevelopmental disorders. Diagnosis relies on the detection of pyrimidine degradation metabolites, such as N-carbamyl-β-alanine (NCβA) and N-carbamyl-β-aminoisobutyrate (NCβAIBA), which are not widely available in routine clinical practice. We report a 7-year-old boy with early-onset developmental delay and regression, Leigh-like basal ganglia lesions on brain MRI, and persistent elevation of urinary methylmalonic acid (MMA). Muscle biopsy revealed an isolated respiratory chain complex I deficiency. Genetic testing identified two novel biallelic UPB1 variants, and urinary analysis confirmed marked elevation of pyrimidine degradation metabolites, establishing the diagnosis of βUP deficiency. This case expands the clinical and neuroradiological spectrum of βUP deficiency and identifies elevated urinary MMA as a previously unreported finding in this disorder. Given the widespread availability of urinary organic acid analysis, MMA may represent a possibly useful and accessible biomarker to support diagnosis. βUP deficiency should be considered in the differential diagnosis of children with Leigh-like encephalopathy and unexplained MMA elevation.
Ferrera et al. (Fri,) studied this question.