Newborn screening and gene mutations of patients with propionic acidemia in Xuzhou City

Abstract

Objective To study the newborn screening program, morbidity, laboratory findings, gene mutations, treatment and follow-up of neonatal propionic academia (PA) in Xuzhou City. Method From September 2015 to September 2018, the blood sample of neonates from newborn screening program in Xuzhou were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) method to examine the blood acylcarnitine level. The diagnosis was confirmed by urine gas chromatography mass spectrometry (GC-MS) and gene analysis. The clinical manifestation, laboratory findings, gene analysis, treatment and prognosis were retrospectively analyzed. Result A total of 297 610 live birth infants blood samples were screened using MS/MS, and 8 cases were diagnosed with PA, with a prevalence of 1:37 201. Among the 8 patients, 7 had no clinical symptoms before the diagnosis and one already had symptoms including recurrent vomiting, drowsiness, tachypnea and hypotonia. Gene analysis revealed that 6 cases carried propionyl-CoA carboxylase α (PCCA) gene mutations and 2 cases carried propionyl-CoA carboxylase β (PCCB) gene mutations. A total of 10 types of PCCA gene mutations were detected, including 5 missense mutations, 4 splicing mutations and 1 synonymous mutation, among which 7 were de-novo mutations. A total of 4 types of PCCB gene mutations were detected, including 2 missense mutations, 1 frameshift duplication and 1 splicing mutation, among which 3 were de-novo mutations. 1 patient died after refusing treatments. The other 7 cases showed significant decline of the blood propionyl-carnitine level, the ratio of propionyl-carnitine to acetylcarnitine, 3-OH-propionate and methylcitrate level in urine after treatment. 4 cases had normal growth and development, and 3 cases showed various psychomotor retardation on follow-up. Conclusion Newborn screening using LC-MS/MS method is important for early diagnosis of PA. The incidence of PA is relatively high in Xuzhou City. The major clinical manifestations of PA were neurological symptoms. The main cause is PCCA gene defects and missense mutation is most common. Key words: Propionic acidemia; Chromatography, liquid; Gas chromatography-mass spectrometry; Gene mutation