Propionic Acidemia: An Ambispective Cohort Study on Phenotypic and Genotypic Characteristics at a Tertiary Center in
Diep Minh Quang1,2, Chi Dung Vu1,3, Khanh Ngoc Nguyen1,3
1Hanoi Medical University, 1st Ton That Tung Street, Hanoi 11520, Vietnam.
Abstract:
Background/objective: Propionic acidemia (PA), an autosomal recessive metabolic disorder, is caused by biallelic pathogenic variants in the PCCA or PCCB genes. In Vietnam, molecular analyses of PA have been scarce. Hence, the objective of this study was to investigate the phenotypic and genotypic characteristics and clinical management of Vietnamese children with PA. Methods: An ambispective descriptive cohort study was conducted on 14 children who were diagnosed with PA at the Vietnam National Children's Hospital. Collected data encompassed clinical manifestations, biochemical profiles, imaging characteristics, genetic findings, clinical management, and outcomes. Results: Symptom onset within the cohort spanned the neonatal, early infantile, and early childhood periods, with a median age at onset of 7.50 months (range 0.33-34.00 months). The clinical phenotype was characterized by acute encephalopathy, accompanied by lethargy (64.3%), vomiting (57%), and seizures (43%). Even though all tested cases exhibited abnormal urinary organic acids and elevated propionylcarnitine (C3) concentration, other key laboratory findings comprised hyperammonemia (100%), metabolic acidosis (64%), and hematological alterations (64%). The study identified eight pathogenic or likely pathogenic PCCB variants and two variants of uncertain significance, with the c.1124C>T being the most frequently identified variant. This cohort had severe clinical outcomes, as neurodevelopmental impairment was observed in 79% of cases with a mortality rate of 43%. Conclusions: This study underscores the severe clinical and biochemical characteristics of PA in 14 Vietnamese children, reinforcing the necessity of early detection and comprehensive long-term care for PA patients. Furthermore, the identification of 10 PCCB variants, including the recurrent c.1124C>T, p.(Ala375Val) variant in our cohort, broadens the known PCCB variant spectrum.
