OBJECTIVE: To report on the clinical, metabolic and genetic characteristics of a child with carnitine palmitoyl transferase 1A (CPT1A) deficiency. METHODS: Clinical data and the level of acylcarnitine for a child who initially presented as epilepsy were analyzed. Genomic DNA was extracted from peripheral blood samples of the child and her parents and subjected to next-generation sequencing (NGS). RESULTS: Mass spectrometry of blood acylcarnitine indicated increased carnitine 0 (C0) and significantly increased C0/ (C16+C18). DNA sequencing revealed that the child has carried compound heterozygous variants of the CPT1A gene, namely c.1846G>A and c.2201T>C, which were respectively inherited from her mother and father. CONCLUSION CPT1A presenting initially as epilepsy was unreported previously. Analysis of blood acylcarnitine C0 and C0/ (C16 + C18) ratio and NGS are necessary for the identification and diagnosis of CPT1A deficiency. The c.1846G>A and c.2201T>C variants of the CPT1A gene probably underlay the disease in this child. Above finding has also enriched the spectrum of CPT1A gene variants.
Carnitine/blood* ; Carnitine O-Palmitoyltransferase/genetics* ; Child ; DNA Mutational Analysis ; Female ; Humans ; Hypoglycemia/genetics* ; Lipid Metabolism, Inborn Errors/genetics*

PURPOSE: To determine the efficacy of CarnitilR (acetylcarnitine, Hanmi, Korea) therapy in idiopathic oligoasthenospermic men. MATERIALS AND METHODS: Forty-four subfertile men with abnormal semen parameters were treated between March, 2003 and March, 2004 with 3 g of CarnitilR daily for 3 months. Changes in semen parameters were evaluated 3 months after this therapy. RESULTS: The mean age was 34.2 years and the mean follow-up duration was 3.7 months. In asthenospemic patients (n=28), semen analysis before and after CarnitilR treatment showed an increase in volume (2.64+/-1.65 ml vs. 3.10+/-1.60 ml), motility (35.1+/-17.7% vs. 45.9+/-20.4%) and viability (51.4+/-20.3% vs. 59.3+/-13.6%) respectively. In oligoasthenospermic patients (n=16), semen analysis before and after CarnitilR treatment showed an increase in sperm count (10.7+/-54.4 million/ml vs. 38.4+/-32.5 million/ml) respectively. CONCLUSIONS: These results suggested that in idiopathic oligoasthenospermic men the empirical medical therapy with acetylcarnitine may be considered as primary treatment.
Acetylcarnitine* ; Carnitine ; Follow-Up Studies ; Humans ; Infertility, Male ; Male ; Semen ; Semen Analysis ; Sperm Count

The fatty acid composition of spermatozoa has been shown to be important for their function, and L-carnitine is crucial for fatty acid metabolism. Its levels in the seminal plasma positively correlate with semen quality, whereas high body mass index (BMI) is associated with both reduced semen quality and altered sperm fatty acid composition. Here, we examined the associations between free seminal L-carnitine levels and sperm fatty acid composition as well as BMI. Semen samples were collected and analyzed from 128 men with unknown fertility status and with BMI ranging from 19 kg m^-2 to 63 kg m^-2. Sperm fatty acid composition was assessed by gas chromatography, while free seminal L-carnitine analysis was performed using high-performance liquid chromatography. Multiple linear regression analysis showed a positive correlation of free seminal L-carnitine levels with the amount of sperm palmitic acid (β = 0.21; P = 0.014), docosahexaenoic acid (DHA; β = 0.23; P = 0.007), and total n-3 polyunsaturated fatty acids (β = 0.23; P = 0.008) and a negative correlation of free seminal L-carnitine levels with lignoceric acid (β = -0.29; P = 0.001) and total n-6 polyunsaturated fatty acids (β = -0.24; P = 0.012) when adjusted for covariates. There was no relationship between free seminal L-carnitine levels and BMI. Since free seminal L-carnitine levels are associated with semen quality, the absence of a correlation with BMI suggests that reduced semen quality in obese men is independent of seminal L-carnitine.
Carnitine ; Docosahexaenoic Acids ; Fatty Acids ; Humans ; Male ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa

OBJECTIVETo evaluate the correlation of the level of free L-carnitine with accessory gland markers and its clinical significance.

METHODSSemen samples from 30 fertile men and 222 infertile patients were collected by masturbation. The measurement of the semen quality was carried out by computer-assisted semen analysis system. The seminal plasma components of free L-carnitine, alpha-glucosidase, fructose and acid phosphatase were determined. The results obtained were statistically calculated with an SPSS 12.0 program to evaluate the difference between the control group and the infertile one and the correlation of the free L-carnitine levels with the seminal plasma components of alpha-glucosidase, fructose and acid phosphatase.

RESULTSThe concentration of free L-carnitine (P < 0.01) and the activity of alpha-glucosidase (P < 0.05) were significantly reduced in the infertile group as compared with the control, with no significant difference in the concentration of fructose and the activity of acid phosphatase between the two groups. There was a statistically significant positive correlation between seminal plasma free L-carnitine level and alpha-glucosidase activity (r = 0.504, P < 0.001.

CONCLUSIONThe determination of free L-carnitine level in seminal plasma is a useful test in the evaluation of epididymal function, which may serve as a guidance for the clinical treatment of male infertility as well as for the study on the mechanisms of male reproduction.

Acid Phosphatase ; analysis ; metabolism ; Adult ; Carnitine ; analysis ; metabolism ; Case-Control Studies ; Fructose ; analysis ; Humans ; Infertility, Male ; metabolism ; physiopathology ; Male ; Semen ; chemistry ; alpha-Glucosidases ; analysis

3-methylcrotonyl-CoA carboxylase deficiency is an autosomal recessive disorder characterized by a defect in leucine catabolism. We report the case of an 80-day-old patient with 3-methylcrotonyl-CoA carboxylase deficiency who had elevated levels of 3-hydroxyisovalerylcarnitine (45.56 micromol/L; reference range, <0.65 micromol/L), which was detected using tandem mass spectrometry during newborn screening, and elevated levels of 3-hydroxyisovaleric acid (375.75 mmol/mol Cr) and 3-methylcrotonylglycine (502.36 mmol/mol Cr ), which were detected in urine organic acid analysis. We performed direct sequence analysis of all the exons of the MCCC1 and MCCC2 genes. No mutations were detected in the direct sequence analysis of MCCC1. However sequencing of the MCCC2 gene revealed a mutation caused by a heterozygous G to C transversion [c.313G>C (p.Gly105Arg)] at nucleotide position 313 and a mutation caused by a heterozygous A to T transversion [c.1252A>T (p.lle418Phe)] at nucleotide position 1252. Identification of these 2 novel MCCC2 gene mutations in our patient suggested that analysis of the MCCC1 and MCCC2 genes might prove useful in the diagnosis of 3-methylcrotonyl-CoA carboxylase deficiency.
Carnitine ; Exons ; Glycine ; Humans ; Infant, Newborn ; Leucine ; Mass Screening ; Reference Values ; Sequence Analysis ; Tandem Mass Spectrometry ; Valerates

OBJECTIVETo investigate the fat emulsion tolerance in preterm infants of different gestational ages in the early stage after birth.

METHODSA total of 98 preterm infants were enrolled and divided into extremely preterm infant group (n=17), early preterm infant group (n=48), and moderate-to-late preterm infant group (n=33). According to the dose of fat emulsion, they were further divided into low- and high-dose subgroups. The umbilical cord blood and dried blood filter papers within 3 days after birth were collected. Tandem mass spectrometry was used to measure the content of short-, medium-, and long-chain acylcarnitines.

RESULTSThe extremely preterm infant and early preterm infant groups had a significantly lower content of long-chain acylcarnitines in the umbilical cord blood and dried blood filter papers within 3 days after birth than the moderate-to-late preterm infant group (P<0.05), and the content was positively correlated with gestational age (P<0.01). On the second day after birth, the low-dose fat emulsion subgroup had a significantly higher content of short-, medium-, and long-chain acylcarnitines than the high-dose fat emulsion subgroup among the extremely preterm infants (P<0.05). In the early preterm infant and moderate-to-late preterm infant groups, there were no significant differences in the content of short-, medium-, and long-chain acylcarnitines between the low- and high-dose fat emulsion subgroups within 3 days after birth.

CONCLUSIONSCompared with moderate-to-late preterm infants, extremely preterm infants and early preterm infants have a lower capacity to metabolize long-chain fatty acids within 3 days after birth. Early preterm infants and moderate-to-late preterm infants may tolerate high-dose fat emulsion in the early stage after birth, but extremely preterm infants may have an insufficient capacity to metabolize high-dose fat emulsion.

Carnitine ; analogs & derivatives ; blood ; Fat Emulsions, Intravenous ; analysis ; metabolism ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; metabolism

Human seminal plasma is rich in potential biological markers for male infertility and male reproductive system diseases, which have an application value in the diagnosis and treatment of male infertility. The methods for the detection of semen biochemical markers have been developed from the manual, semi-automatic to the present automatic means. The automatic detection of semen biochemical markers is known for its advantages of simple reagent composition and small amount of reagents for each test, simple setting of parameters, whole automatic procedure with few errors, short detection time contributive to batch detection and reduction of manpower cost, simple calibration and quality control procedure to ensure accurate and reliable results, output of results in the order of the samples in favor of clinical diagnosis and treatment, and open reagents applicable to various automatic biochemistry analyzers. At present, the automatic method is applied in the detection of such semen biochemical markers as seminal plasma total and neutral alpha-glucosidase, acid phosphatase, fructose, γ-glutamyl transpeptidase, zinc, citric acid, uric acid, superoxide dismutase and carnitine, sperm acrosin and lactate dehydrogenase C4, and semen free elastase, which can be used to evaluate the secretory functions of the epididymis, seminal vesicle and prostate, sperm acrosome and energy metabolism function, seminal plasma antioxidative function, and infection or silent infection in the male genital tract.
Acid Phosphatase ; analysis ; Biomarkers ; analysis ; Carnitine ; analysis ; Citric Acid ; analysis ; Epididymis ; metabolism ; Fructose ; analysis ; Humans ; Infertility, Male ; diagnosis ; Isoenzymes ; L-Lactate Dehydrogenase ; Male ; Prostate ; metabolism ; Semen ; chemistry ; Seminal Vesicles ; Spermatozoa ; chemistry ; alpha-Glucosidases ; analysis ; gamma-Glutamyltransferase ; analysis

OBJECTIVE: To explore effects of different delivery and storage conditions on concentrations of amino acids and carnitines in neonatal dried blood spots (DBS), so as to provide evidence for improving accurate and reliable detection by tandem mass spectrometry. METHODS: A total of 1 254 616 newborn DBS samples in Newborn Screening Center of Zhejiang Province were delivered and stored at room temperature (group A, RESULTS: The concentrations of amino acids and carnitines in the three groups were skewed, and the differences in amino acid and carnitine concentrations among groups were statistically significant (all CONCLUSIONS Cold-chain logistics system and storage in low temperature and low humidity can effectively reduce degradation of some amino acids and carnitines in DBS, improve the accuracy and reliability of detection, and thus ensures the quality of screening for neonatal metabolic diseases.
Amino Acids/analysis* ; Carnitine/analysis* ; Dried Blood Spot Testing/standards* ; Humans ; Humidity ; Infant, Newborn ; Neonatal Screening ; Reproducibility of Results ; Specimen Handling/standards* ; Tandem Mass Spectrometry ; Temperature ; Time Factors

OBJECTIVETo evaluate the effect and safety of L-carnitine in the treatment of idiopathic oligoasthenozoospermia based on current clinical evidence.

METHODSWe searched the Cochrane Library, PubMed, MEDLINE, EMBASE, CNKI, VIP, CBM and Wanfang Database from the establishment to April 2014 for the published literature on the treatment of idiopathic oligoasthenozoospermia with L-carnitine. We conducted literature screening, data extraction, and assessment of the methodological quality of the included trials according to the inclusion and exclusion criteria, followed by statistical analysis with the RevMan 5. 2 software.

RESULTSSeven randomized controlled trials involving 751 patients with idiopathic oligoasthenozoospermia met the inclusion criteria, and 678 of them were included in the meta-analysis. L-carnitine treatment achieved a significantly increased rate of spontaneous pregnancy as compared with the control group (RR = 3.2, 95% CI 1.74 to 5.87, P = 0.0002). After 12-16 and 24-26 weeks of medication, total sperm motility (WMD = 5.21, 95% CI 2.78 to 7.64, P < 0.0001 and WMD = 9.29, 95% CI 1.28 to 17.29, P = 0.02) and the percentage of progressively motile sperm (WMD = 12.44, 95% CI 4.58 to 20.31, P = 0.002 and WMD = 9.76, 95% CI 3.56 to 15.97, P = 0.002) were remarkably higher than those in the control group, but no statistically significant differences were observed in sperm concentration between the two groups (WMD = 4.91, 95% CI -2.63 to 12.45, P = 0.2 and WMD = 0.93, 95% CI -3.48 to 5.34, P = 0.68). After 12-16 weeks of treatment, the percentage of morphologically abnormal sperm was markedly decreased in the L-carnitine group as compared with the control (WMD = -2.48, 95% CI -4.35 to -0.61, P = 0.009), but showed no significant difference from the latter group after 24-26 weeks (WMD = -4.38, 95% CI -9.66 to 0.89, P = 0.1). No statistically significant difference was found in the semen volume between the two groups after 12-16 or 24-26 weeks of medication (WMD = -0.13, 95% CI -0.43 to 0.18, P = 0.42 and WMD = 0.28, 95% CI -0.02 to 0.58, P = 0.07). No serious L-carnitine-related adverse events were reported in 4 of the randomniized controlled trials.

CONCLUSIONThe current evidence indicates that L-carnitine can improve spontaneous pregnancy and semen parameters in the treatment of idiopathic oligoasthenozoospermia, with no serious adverse reactions.

Asthenozoospermia ; drug therapy ; Carnitine ; adverse effects ; pharmacology ; Female ; Humans ; Male ; Pregnancy ; Pregnancy Rate ; Randomized Controlled Trials as Topic ; Semen Analysis ; Sperm Count ; Sperm Motility

Medium- and short-chain acyl-CoA dehydrogenase deficiency is a disorder of fatty acid β-oxidation. Gene mutation prevents medium- and short-chain fatty acids from entry into mitochondria for oxidation, which leads to multiple organ dysfunction. In this study, serum acylcarnitines and the organic acid profile in urea were analyzed in two children whose clinical symptoms were hypoglycemia and metabolic acidosis. Moreover, gene mutations in the two children and their parents were evaluated. One of the patients was a 3-day-old male who was admitted to the hospital due to neonatal asphyxia, sucking weakness, and sleepiness. The serum acylcarnitine profile showed increases in medium-chain acylcarnitines (C6-C10), particularly in C8, which showed a concentration of 3.52 μmol/L (reference value: 0.02-0.2 μmol/L). The analysis of organic acids in urea gave a normal result. Sanger sequencing revealed a reported c.580A>G (p.Asn194Asp) homozygous mutation at exon 7 of the ACADM gene. The other patient was a 3-month-old female who was admitted to the hospital due to cough and recurrent fever for around 10 days. The serum acylcarnitine profile showed an increase in serum C4 level, which was 1.66 μmol/L (reference value: 0.06-0.6 μmol/L). The analysis of organic acids in urea showed an increase in the level of ethyl malonic acid, which was 55.9 (reference value: 0-6.2). Sanger sequencing revealed a reported c.625G>A (p.Gly209Ser) homozygous mutation in the ACADS gene. This study indicates that screening tests for genetic metabolic diseases are recommended for children who have unexplained metabolic acidosis and hypoglycemia. Genetic analyses of the ACADM and ACADS genes are helpful for the diagnosis of medium- and short-chain acyl-CoA dehydrogenase deficiency.
Acyl-CoA Dehydrogenase ; deficiency ; genetics ; Carnitine ; analogs & derivatives ; blood ; Female ; Humans ; Infant ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; genetics ; Male ; Mutation ; Urea ; analysis