Analysis on clinical characteristics and mutation characteristics of SLC22A5 gene in neonates with primary carnitine deficiency

Yue Mengting; Huang Xiang; Shao Qiaoyi; Yu Feng; Wang Jianyu

doi:10.3969/j.issn.1674-7151.2025.04.016

Abstract：Objective To explore the blood tandem mass spectrometry indexes of newborns with primary carnitine deficiency(PCD)in Foshan City,Guangdong Province,improve the sensitivity of early screening,analyze the characteristics of SLC22A5 gene mutation spectrum and serum biochemical indicators,and provide scientific basis for the early diagnosis and precise treatment of PCD in the region.Methods The samples of heel blood were collected from neonates in 38 midwifery institutions in Foshan City from January 2020 to December 2024 to screen multiple inherited metabolic diseases using tandem mass spectrometry.The suspected neonates with free carnitine(C0)<laboratory cut-off value and their mothers were recalled simultaneously,and gene detection was performed on those with re-screening results positive.For neonates confirmed with PCD,positive rates of clinical biochemical indexes[lactate dehydrogenase(LDH)and total bile acid(TBA)]and gene mutation characteristics were analyzed.Results Among the 305 297 neonates undergoing tandem mass spectrometry screening,there were 638 cases with blood C0<normal reference value(cut-off value C0<12 μmol/L)and 542 cases were recalled,with a recall rate of 84.9%.There were 12 neonates diagnozed with PCD,with an incidence of 0.004%.The data analysis showed that C0 level was relatively low,which was(3.66-10.15)μmol/L in the initial screening,and C0 was positively correlated with 16-acylcarnitine(C16;r=0.750,P=0.005).In neonates with PCD,there were 3 mothers with C0 decrease(<14.00 μmol/L),3 mothers with normal C0 and 2 mothers with C16 or 18-acylcarnitine(C18)abnormality.After levocarnitine treatment,C0 level was significantly higher than that before treatment(μmol/L:31.33±11.77 vs.7.28±2.11,P<0.001).Among the 542 neonates with initial screening and re-screening results positive,there were 10 types of SLC22A5 gene mutation,and incidence of c.51C>G(p.F17L)and c.1400C>G(p.S467C)mutation was higher[both accounting for 50.0%(6 cases)].All families were conformed to autosomal recessive inheritance pattern.There were 5 mutation carriers,and frequency of c.51C>G(p.F17L)mutation was 3 times,accounting for 60.0%.The biochemical examination results showed that the positive detection rates of LDH and TBA were both 58.33%(7/12).Conclusions There are specific lineage characteristics of gene mutation in neonates with PCD in Foshan City,c.51C>G and c.1400C>G are main mutation hotspots.Tandem mass spectrometry combined with genetic analysis can effectively increase early diagnostic rate,LDH and TBA can be applied as auxiliary diagnostic indexes.Levocarnitine treatment is effective for PCD,but long-term standardized treatment and follow-up are also necessary.