Propionic Acidemia in a One-Month-Old Infant: A Clinical Case Report

Propionic acidemia (PA) is a rare inherited metabolic disorder caused by a deficiency of propionyl-CoA carboxylase, encoded by the pcca and pccb genes. Despite PA being included in international newborn screening programs, cases of delayed diagnosis still occur, especially in countries where mass screening does not cover all metabolic disorders. The clinical manifestations of PA can mimic common somatic or surgical conditions, which complicates timely diagnosis and increases the risk of adverse outcomes. This case report illustrates successful diagnosis and treatment of PA in a newborn whose initial symptoms were interpreted as gastrointestinal pathology.

During the first month of life, the patient presented with profuse regurgitation, poor appetite, failure to gain weight, and episodes of lethargy and tremor. These symptoms initially led to investigations for pyloric stenosis and other gastrointestinal conditions. However, subsequent biochemical and instrumental evaluations revealed hyperammonemia, elevated propionylcarnitine (C3), and increased C3/C2 and C3/C16 ratios, raising suspicion of an organic acidemia. Whole exome sequencing identified compound heterozygous variants in the pcaa gene, both of uncertain clinical significance: c.734C>T (p.Ser245Leu) and c.1351A>G (p.Lys451Glu). Family Sanger sequencing confirmed heterozygous carriage of c.734C>T (p.Ser245Leu) in the father, and c.1351A>G (p.Lys451Glu) in both the mother and the patient’s healthy sister. The diagnosis of “propionic acidemia” was established based on the clinical, biochemical, and genetic findings. The patient received specialized treatment, including amino acid-restricted diet, carnitine, biotin, hydration, and symptomatic management. Clinical condition improved, and at the age of 7 months, the child demonstrated age-appropriate development without neurological deficits.

This clinical case underscores the importance of early diagnosis of PA and highlights the value of tandem mass spectrometry as a part of neonatal screening. Despite the nonspecific nature of early symptoms, clinical vigilance and a comprehensive diagnostic approach can lead to timely diagnosis before irreversible complications arise. The case illustrates the diagnostic utility of integrating biochemical and molecular methods and emphasizes the need for a multidisciplinary approach.