{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "Child Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Lombardy, Italy",
        "Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Lombardy, Italy"
      ],
      "name": "Giulia Ferrera"
    },
    {
      "affiliations": [
        "Division of Metabolic Diseases and Hepatology, Bambino Gesù Pediatric Hospital, IRCCS, Rome, Lazio, Italy"
      ],
      "name": "Sara Boenzi"
    },
    {
      "affiliations": [
        "Unit of Medical Genetics and Neurogenetics - Mariani Foundation Centre for Paediatric Mitochondrial Disorders, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Lombardy, Italy"
      ],
      "name": "Eleonora Lamantea"
    },
    {
      "affiliations": [
        "Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Lombardy, Italy",
        "Unit of Medical Genetics and Neurogenetics - Mariani Foundation Centre for Paediatric Mitochondrial Disorders, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Lombardy, Italy"
      ],
      "name": "Daniele Ghezzi"
    },
    {
      "affiliations": [
        "Child Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Lombardy, Italy"
      ],
      "name": "Anna Ardissone"
    }
  ],
  "title": "β-ureidopropionase deficiency mimicking Leigh syndrome associated with methylmalonic aciduria",
  "uid": "8a3576d9-ca19-53e0-a726-74dbf1b93e3d"
}