Evaluation of the Clinical, Biochemical, Genotype, and Prognosis of Propionic Acidemia in 133 Patients from China

Background Propionic acidemia (PA) is an inherited organic acid metabolic disease involving multiple physiological systems with variable manifestations. The causative genes, PCCA and PCCB, carry a wide range of mutations. The present study aimed to investigate the phenotype and genotype features of PA in Chinese patients. Methods We enrolled 133 PA patients who were treated during the past 17 years. We investigated their clinical data in detail, including national newborn screening (NBS) status and disease onset, biochemical metabolites, gene variations, and recent prognosis, to investigate the phenotype and genotype features. Results Among the 133 PA patients, 36 patients were diagnosed thanks to NBS expanded by tandem mass spectrometry (MS/MS). The median onset time was four months old, with symptoms involving multiple systems without specificity. The blood propionylcarnitine/ acetylcarnitine (C3/C2) ratio and urine 3-hydroxypropionic acid (3-OHPA) levels decreased after treatment. The overall prognosis of was poor, with 25.5% being healthy (34/133), 36.1% having developmental delays (48/133), 24.1% dying (32/133) and 14.3% being lost to follow-up (19/133). In the PCCA gene of 49 patients, 60 variants were detected, including 43 new variations. The variations c.2002G > A, c.229C > T, and c.1118T > A were the three most frequent variations. In the PCCB gene of 80 patients, 64 variants were detected, including 40 new variations. The variations c.1087T > C, c.838dup, and c.1228C > T were the three most frequent variations. Conclusion PA is a serious organic acidemia with early onset and nonspecific symptoms. The overall prognosis is poor. There are wide and relative common variations in Chinese patients in causative genes.