Intermittent maple syrup urine disease (MSUD) uncovered by screening

Background: Intermittent MSUD is a mild form of the disease with patients displaying no symptoms and having normal metabolic investigations including branched chain amino acids (leucine, isoleucine, valine) but still running the risk of a potentially fatal crisis

Case Study: A female infant was referred because of abnormal neonatal biochemical screening results (normal amino acids but increased Leu/Phe and Fischer ratios) performed on a private basis followed by a genetic screening panel showing compound heterozygosity for two missense variants in the BCKDHB gene. She is the first offspring of unrelated parents, growing well on breastmilk supplemented with formula and without any symptoms or clinical findings related to MSUD. Common investigations, ammonia, plasma amino acids, urine organic acids plus confirmation of the mutations in the family via Sanger sequencing were performed. The baby was put on regular follow up without any dietary restrictions.

Results: Initial plasma amino acids showed repeatedly borderline high leucine values (217umol/l, upper normal 200umol/l). All other investigations were normal and no alloisoleucine was detected. Sanger sequencing confirmed the presence of the paternal variant c.832G>A p.(Gly278Ser) associated with a non-classic phenotype and the maternal likely pathogenic variant c.528C>G p.(Asn176Lys). At the age of 5.5 months, amino acids showed increased leucine 283umol/l and isoleucine 127umol/l and the presence of alloisoleucine for the first time. At 10 months of age, the patient remains asymptomatic with the family exercising a protein conscious diet and having an emergency protocol.

Discussion/ Conclusion: Early diagnosis by screening programs has optimized the patient’s prognosis and the family’s planning. The universal application of neonatal screening by the state will ensure optimal health and minimize complications. New information on different phenotypes will emerge as a result.