Biochemical and genetic characteristics of 40 neonates with carnitine deficiency / 中南大学学报(医学版)

OBJECTIVES@#Primary carnitine deficiency (PCD) is a rare fatty acid metabolism disorder that can cause neonatal death. This study aims to analyze carnitine levels and detect SLC22A5 gene in newborns with carnitine deficiency, to provide a basis for early diagnosis of PCD, and to explore the relationship between carnitine in blood and SLC22A5 genotype.@*METHODS@#A total of 40 neonates with low free carnitine (C0G (p.Y251C), c.495 C>A (p.R165E), and c.1298T>C (p.M433T). We found 14 PCD patients including 2 homozygous mutations and 12 heterozygous mutations, 14 with 1 mutation, and 12 with no mutation among 40 children. The C0 concentration of children with SLC22A5 gene homozygous or complex heterozygous mutations was (4.95±1.62) μmol/L in the initial screening, and (3.90±1.33) μmol/L in the second screening. The C0 concentration of children with no mutation was (7.04±2.05) μmol/L in the initial screening, and (8.02±2.87) μmol/L in the second screening. There were significant differences between children with homozygous or compound heterozygous mutations and with no mutation in C0 concentration of the initial and the second screening (both @*CONCLUSIONS@#There are 5 new mutations which enriched the mutation spectrum of SLC22A5 gene. C0<5 μmol/L is highly correlated with SLC22A5 gene homozygous or compound heterozygous mutations. Children with truncated mutation may have lower C0 concentration than that with untruncated mutation in the initial screening.

Screening and SLC22A5 gene mutations of the patients with primary carnitine deficiency / 中华实用儿科临床杂志

Objective To investigate the clinical features and SLC22A5 gene mutation types in patients with primary carnitine deficiency(PCD).Methods The free carnitine(CO) and acylcarnitine levels in the blood of 210 908 neonates from newborn screening program and 576 children with suspected clinical inherited metabolic diseases were measured by using liquid chromatography tandem mass spectrometry method during September 2015 to December 2017,after that the SLC22A5 gene mutations were analyzed in the children with low CO level and the diagnosis was made.The clinical characteristics,laboratory findings,genotypes,treatment and prognosis were retrospectively analyzed in patients.Paired sample t test was used to compare the biochemical indexes of patients before and after the treatments.Results Ten children were diagnosed with PCD(9 cases from newborn screening program,1 case from clinical patients),and 7 children were diagnosed with maternal carnitine deficiency.After treatment with oral Levocarnitine,the free carnitine and acylcarnitine of the patients returned to the normal levels.The clinical symptoms disappeared in 1 patient out of clinical patients,and the other 16 patients from newborn screening program were asymptomatic and showed normal growth and development.Seventeen patients got genetic analysis,and 10 types of mutations were found,including c.1400C ＞ G,c.1462C ＞ T,c.797C ＞ T,c.95A ＞ G,c.92C ＞ T,c.1093A ＞ C,c.761G ＞ A,c.865C ＞ T,c.428C ＞ T,c.1195C ＞ T,among which two of them (c.1093A ＞ C and c.92C ＞ T) were novel mutations.The most common mutation of SLC22A5 gene was c.1400C ＞ G.Conclusions Liquid chromatography tandem mass spectrometry technology is sufficient to screen newborns and maternal carnitine deficiency,and the c.1400C ＞ G mutation is found at the highest frequency in Xuzhou area.If patients receive early treatment,they may have a good prognosis.

Clinical and gene analysis of primary carnitine deficiency found by neonatal screening / 临床儿科杂志

Objective To explore the clinical feature and gene types in patients with primary carnitine deficiency. MethodsClinical data of 6 patients with primary carnitine deficiency and 2 patients with maternal carnitine deficiency found in the screening by tandem mass spectrometry technology during December 2013 to December 2016 were retrospectively analyzed. Results The free carnitine levels of 8 patients in initial and recall screening were 5.85±1.65 μmol/L and 5.22±1.02 μmol/L. Two pathogenic alleles were detected in each patient with primary carnitine deficiency by genetic and metabolic disease panel based on Ion Torrent semiconductor sequencing. After treatment with oral L-carnitine, the free carnitine levels of 6 patients with primary carnitine deficiency were 20.24±3.88 μmol/L. The carnitine levels returned to normal after mixed feeding for one week in 2 patients with maternal carnitine deficiency, and no genetic diagnosis was carried out. Conclusion Primary carnitine deficiency can be effectively detected using tandem mass spectrometry technology and next generation sequencing panel and the prognosis is good with early standard treatment.

The SLC22A5 genetic analysis in Chinese patients with systemic primary carnitine deficiency / 中华内分泌代谢杂志

Objective To investigate the clinical and biochemical metabolic features of 12 patients with systemic primary carnitine deficiency(CDSP) and to identify the SLC22A5 gene mutation types of the disease. Method The clinical and biochemical data were collected by retrospective analysis. DNA direct sequencing and multiplex ligation dependent probe amplification(MLPA)were applied for SLC22A5 gene analysis. Result Among 12 patients with CDSP, 3 cases had evident infection factors, 6 cases with convulsions, 5 cases manifested liver hypertrophy, 8 cases with hyperammonemia, and 9 cases showed myocardial damage. All CDSP patients were detected biallelic pathogenic mutation in SLC22A5 gene by direct sequencing. The gene types include IVS2+1G>T, c.3G>T(p.Met1Ile), c.760C>T(p.Arg254X), c.1400C>G(p.Ser467Cys), c.844dupc(p.Arg282fs), c.338G>A(p.Cys113Tyr), c.51C>G(p.Phe17Leu), c.659A>T(p.Glu220Val), and c.1365dupC(p.Thr456fs). c.659A>T(p.Glu220Val) and c.1365dupC(p.Thr456fs)are novel mutations. One female patient was maternal CDSP, her child had abnormal newborn screening. The allele frequency of c.760C>T(p.Arg254X) and c.1400C>G(p.Ser467Cys) were 37.5%(9/24)and 29.2%(7/24)respectively. The MLPA test results of all patients were negative. Conclusion The clinical manifestations are complex and various in patients with CDSP. Point and small InDel(insertions/deletions)mutation constitute the major alteration in SLC22A5 gene. c.1400C>G(p.Ser467Cys) might be another prevalence mutation type in Chinese CDSP patient.

The effects of additional L-carnitine supplement on plasma free carnitine in preterm infants and its clinical significance / 实用医学杂志

Objective To investigate the changes of plasma free carnitine (FC) concentrations in preterm infants supplemented with L-carnitine, and to provide a reference for routine preterm infants L-carnitine supplements. Methods A total of 99 preterm infants supplemented with 10 mg/(kg·d) L-carnitine on days 2 and 5 after birth, and 65 full term infants from Department of Neonatology, the Fifth People′s Hospital of Dongguan during July 2014 to December 2015 were recruited in this study , and filter-paper blood spots were collected by heel prick on days 1, 3 and 7. FC was measured using electron spray ionization (ESI) tandem mass spectrometry (MS-MS). Results Concentrations of FC decreased steadily from day 1 to day 7 in full term infants , while it remained the same level during the first week after birth as at birth. Additionally, concentrations of FC were significantly higher in preterm infants than full term infants on day 1 after birth. Conclusions The reasonable L-carnitine supplements may keep the levels of plasma FC at the levels at birth , which is important for fatty acid metabolism in preterm infants.

Study of changes of free carnitine in premature newborns with hyaline membrane disease / 重庆医学

Objective To study the serum free carnitine level and change trend in premature infantwith hyaline membrane disease (HMD) within postnatal 7 d .MethodTotally 63 preterm newbornwith gestational age of 28-32 weekin the NICU of thihospital were selected ,among them 32 caseof HMD were taken athe observation group and othe31 preterm newbornwithouHMD athe control group .The free carnitine level wameasured within 6 h aftebirth ,on 3 ,7 d by using the tandem masspectrum method .ResultThe free carnitine level within 6 h aftebirth had no statistical difference between the observation group and the control group[(23 .57 ± 7 .45)μmol/L v.(24 .34 ± 5 .73)μmol/L ,t=0 .48 ,P=0 .630] ,the free carnitine level on 3 d in the observation group wasignificantly lowethan thain the control group [(19 .21 ± 6 .83)μmol/L v.(23 .74 ± 7 .13)μmol/L ,t=2 .57 ,P=0 .010];the free carnitine level on 7 d in the observation group waalso significantly lowethan thain the control group [(16 .62 ± 7 .95)μmol/L v.(22 .83 ± 6 .56)μmol/L ,t=3 .39 ,P=0 .001] .The free carnitine level aftebirth in the control group remained stable ,which a3 time pointof 6h ,3 ,7 d had no statistical difference(F=0 .42 ,P=0 .660);whereathe free carnitine level wagradually decreased aftebirth ,which a3 time pointof 6 h ,3 ,7 had statistical difference(F=7 .13 ,P=0 .001) .Conclu-sion The free carnitine level aftebirth in preterm newbornwith HMD igradually decreased ,which needmore carnitine fopromoting the generation of pulmonary surfactan.

Influence of L-carnitine on plasma free carnitine level, blood glucose and blood viscosity in type 2 diabetic patients with hypertension / 第二军医大学学报

Objective:To investigate the changes of plasma free carnitine (FC) level in type 2 diabetes mellitus patients with hypertension and the influence of L-carnitine(L-CN) on plasma FC,blood glucose and blood viscosity. Methods:Plasma FC, blood glucose and blood viscosity were measured in 20 type 2 diabetic patients with hypertension (group 1) and 20 patients with essential hypertension (group 2) before and after they received 3. 0 g/d /,-CN intravenous infusion for ]0 d. Re-sultstlt was observed that plasma FC level was lower in group 1 [(50. 59?13. 41) ?mol/L] than in group 2 [(63. 32? 15. 23) ?mol/L,P