Propionic acidemia in a one-month-old infant: a case report

Propionic acidemia is a rare inherited metabolic disorder associated with impaired function of propionyl-CoA carboxylase, encoded by the PCCA and PCCB genes. Despite the inclusion of propionic acidemia in international neonatal screening programs, cases of delayed diagnosis continue to occur, particularly in countries where population-based screening does not cover the full spectrum of metabolic disorders. The clinical manifestations of propionic acidemia may mimic common somatic or surgical conditions, which complicates timely diagnosis and increases the risk of an unfavorable course. The present report describes a case of successful diagnosis and management of propionic acidemia in a newborn whose initial clinical presentation was interpreted as a gastrointestinal condition. During the first month of life, the patient exhibited frequent regurgitation, poor appetite, failure to gain weight, as well as episodes of lethargy and tremor, prompting evaluation for pyloric stenosis and other gastrointestinal disorders. However, further biochemical and instrumental investigations revealed elevated propionylcarnitine (C3) levels, increased propionylcarnitine-to-acetylcarnitine (C3/C2) and propionylcarnitine-to-palmitoylcarnitine (C3/C16) ratios, raising suspicion of an organic acidemia. Whole-exome sequencing identified compound heterozygous variants of uncertain clinical significance in the PCCA gene: c.734CT (p.Ser245Leu) and c.1351AG (p.Lys451Glu). Sequencing of the unaffected parents and sibling confirmed heterozygous carrier status: c.734CT (p.Ser245Leu) in the father, c.1351AG (p.Lys451Glu) in the mother, and c.1351AG (p.Lys451Glu) in the sister. The diagnosis of propionic acidemia was established based on the totality of clinical, biochemical, and genetic findings. Appropriate therapy, including a specialized amino acid-restricted diet, carnitine and biotin supplementation, hydration, and symptomatic management, was initiated. Following treatment, the patient’s condition stabilized, and at 7 months of age, development was consistent, with no neurological impairment. This clinical case highlights the importance of early diagnosis of propionic acidemia and underscores the role of tandem mass spectrometry in neonatal screening. Despite nonspecific initial symptoms, heightened clinical awareness and a comprehensive diagnostic approach allow for diagnosis before the development of irreversible complications. The case demonstrates the diagnostic value of integrating biochemical and molecular methods and emphasizes the need for a multidisciplinary approach.