Propionic acidemia is an autosomal recessive disorder caused by a defect of propionyl-coenzyme A carboxylase [1]. We report a case of propionic acidemia with fatal outcome and two novel heterozygous PCCA mutations.

A male infant presented to us with vomiting and lethargy at 48 hours of life. He showed metabolic acidosis (pH 6.8, HCO3 10.1 mmol/L, base excess -17 mmol/L), and hyperammonemia (761 µM). Analysis of blood acylcarnitine profile indicated an elevated propionylcarnitine level (17 µM, cutoff <6 µM). The analysis of organic acids in urine by using GC-MS indicated an elevated concentration of 3-Hydroxy-propionic acid (153, cutoff: <1.1) and methylcitric acid (23, cutoff: <1.1). Despite restriction of protein supply, high-caloric nutrition, correction of acidosis, and supplementation of biotin and carnitine, the infant died at 4 days of life. His two elder sisters had died after similar symptoms during the neonatal period. Blood samples from the infant and his parents were tested for genetic- and mutation analysis, after informed consent. Genetic analysis of the infant showed two heterozygous novel missense mutations [PCCA NM_000282.3: c.308T>G (p.V103G), PCCA NM_000282.3: c.809T>C (p.I270T)], and another heterozygous reported missense mutation [PCCA NM_000282.3: c.2002G>A (p.G668A)] in the PCCA gene [2]. The father was heterozygous for c.2002G>A (p.G668A). The mother was heterozygous for c.308T>G (p.V103G) and c.809T>C (p.I270T).

In about 80% of cases of propionic acidemia, clinical onset occurs in the neonatal period. In these patients, mortality is much higher than in the late-onset group. Several studies have addressed the possible genotype-phenotype correlations in propionic acidemia [3]. According to the clinical outcome of the patient in this report, there was a certain correlation between the genotype and the phenotype. A deeper insight of the correlation may be obtained by functional studies of the novel mutations in the PCCA gene.

Funding: The National Natural Science Foundation of China (Grant no. 81741064).

Competing interest: None stated.

1. Chapman KA,　Gropman A,　MacLeod E,　Stagni K,　Summar ML,　Ueda K,　et al. Acute management of　propionic acidemia. Mol Genet Metab.　2012;105:16-25.

2. Campeau E,　Dupuis L,　León-Del-Rio A,　Gravel R. Coding sequence mutations in the alpha subunit of propionyl-CoA carboxylase in patients with propionic　acidemia. Mol Genet Metab.　1999;67:11-22.