Analysis of metabolic profile and genetic variants for newborns with primary carnitine deficiency from Guangxi / 中华医学遗传学杂志

OBJECTIVE@#To analyze the metabolic profile and genetic variants for newborns with primary carnitine deficiency (PCD) from Guangxi, China.@*METHODS@#From January 2014 to December 2019, 400 575 newborns from the jurisdiction of Guangxi Zhuang Autonomous Region Newborn Screening Center were subjected to tandem mass spectrometry (MS/MS) analysis. Newborns with positive results for PCD and their mothers were recalled for retesting. Those who were still positive were subjected to sequencing of the SLC22A5 gene.@*RESULTS@#Twenty-two newborns and 9 mothers were diagnosed with PCD, which gave a prevalence rate of 1/18 208. Sequencing of 18 newborns and 4 mothers have identified 14 types of SLC22A5 gene variants, with the common ones including c.51C>G (10/44, 22.7%), c.1195C>T (9/44, 20.5%) and c.1400C>G (7/44, 15.9%), The c.517delC(p.L173Cfs*3) and c.1031C>T(p.T344I) were unreported previously and predicted to be pathogenic (PVS1+PM2_supporting+PM3+PP4) and likely pathogenic (PM1+PM2_supporting+PM3+PP3+PP4) based on the American College of Medical Genetics and Genomics standards and guidelines.@*CONCLUSION@#c.51C>G, c.1195C>T and c.1400C>G are the most common variants underlying PCD in Guangxi.

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.

Carnitine supplement: does it worth trial to improve semen quality among infertile Sudanese men?

Carnitine supplement proves to upgrade the quality of semen by increasing sperm count and motility. In this study we have determined the level of L - carnitine in the seminal plasma of men with normal and abnormal seminal analysis. L - carnitine levels among the normal group was significantly higher than the abnormal group. We recommend trials of carnitine supplements to evaluate its usefulness in correcting some infertility cases. A total of 52 men, recruited from fertility centers in Khartoum, were included in this study. Colorimetric carnitine determination kits were used for estimation of L - carnitine in seminal plasma. Collectively, men with normal values of semen analysis had significantly higher mean seminal plasma carnitine levels compared to abnormal values [p = 0.028]. Oligospermic men had significantly lower levels of carnitine compared to normal [p = 0.046]. Seminal plasma carnitine level seems to correlate with seminal quality and its deficiency may be a reason for infertility among some Sudanese men

Diagnóstico in vitro de la deficiencia primaria de carnitina / In vitro diagnosis of primary carnitine deficiency

El transportador de carnitina (OCTN2) es fundamental para el metabolismo mitocondrial de los ácidos grasos de cadena larga. Su carencia produce la deficiencia primaria de carnitina. El presente estudio tuvo como objetivo el análisis de los ácidos grasos producidos por fibroblastos incubados en presencia de sustratos deuterados, mediante cromatografía de gases acoplada a espectrometría de masas (GC - MS) como herramienta diagnóstica de la deficiencia primaria de carnitina. Se encontró un perfil característico en esta deficiencia, lo que permite su diagnóstico in vitro.

Carnitine transporter (OCTN2) is required for the mitochondrial metabolism of long-chain fatty acids. Primary carnitine deficiency is a consequence of its deficiency. The objective of the present study was to analyse the fatty acids produced by fibroblasts incubated with deuterated substrates, using gas chromatography-mass spectrometry as a diagnostic tool for the diagnosis of VLCAD deficiency. A characteristic profile for this deficiency was found using this technique which enables its in vitro diagnosis.

[Effects of L-carnitine supplements on inflammatory cytokines, CRP and oxidative stress in hemodialysis patients]

Inflammation and oxidative stress are common in patients with chronic renal disease, including hemodialysis patients. The present study was designed to investigate the effects of L-carnitine supplements on inflammatory cytokines, CRP and oxidative stress in hemodialysis patients. The study was a randomized clinical trial. Thirty-six hemodialysis patients, [23 males and 13 females], were randomly assigned to either carnitine group or the control group. The patients in the carnitine group received 1000 mg/d oral L-carnitine for 12 weeks while the control group did not receive any L-carnitine supplement during the study. At the baseline and the end of 12th week of the study, 5 ml. blood was collected after a 12 to 14-hour fast from each patient before dialysis and then serum free carnitine, CRP, IL-1beta, IL-6, TNF-alpha and ox-LDL were measured. Mean serum free carnitine concentration increased significantly, by 86%, in the carnitine group at the end of 12th week as compared to the baseline [P<0.001], while serum CRP and IL-6 decreased significantly, by 29% [P<0.05] and 61% [P<0.001], respectively. No significant changes were observed in the serum concentrations of free carnitine, CRP and IL-6 in the control group during the study. There were no significant differences between mean changes of serum IL-1beta, TNF-alpha and ox-LDL concentrations in the two groups. This study indicated that L-carnitine supplement could improve carnitine deficiency and decrease inflammatory markers of CRP and IL-6 in hemodialysis patients

Sodium valproate -- induced skeletal myopathy.

The authors report a case of skeletal myopathy in a four-year-old boy on long-term sodium valproate therapy for secondary epilepsy due to neurocysticercosis. He presented with clinical features of limb girdle weakness. EMG revealed features of myopathy. Carnitine deficiency due to sodium valproate was suspected and plasma carnitine levels were found to be low. Sodium valproate was withdrawn. L-carnitine supplementation resulted in marked clinical recovery as well as rise in plasma carnitine levels.

Mitochondrial fatty acid oxidation disorders in Thai infants: a report of 3 cases.

Three infants with documented mitochondrial fatty acid oxidation disorders are described in this report. Case 1. Carnitine/acylcarnitine translocase deficiency. (CACT) (OMIM 212138) A two-day-old male developed sudden cardiac arrest 48 hours postpartum, with a previous history of early death (day 2) in siblings with a history of parental consanguinity; somnolence, inactivity, refusal to suck within 24 h, hepatomegaly, persistent hypoglycemia, hypocalcemia, hyperkalemia and severe metabolic acidosis prior to cardiac arrest. Dried blood spots by tandem mass spectrometry demonstrated 10 x elevation of palmitoylcarnitine, moderate elevation of oleylcarnitine, steroylcarnitine and myristoylcarnitine. Case 2. Medium chain acyl CoA dehydrogenase (MCAD) deficiency. (OMIM 212139) A six-week-old male infant, developed sudden cardiac arrest after contacting a viral illness, resuscitated successfully in the first episode, only to succumb during the second episode, 2 weeks apart. Plasma acylcarnitine via tandem mass spectrometry was reported normal; however, urine organic acids via gas liquid chromatography and mass spectrometry demonstrated characteristic metabolites consistent with MCADD. Case 3. Carnitine deficiency, systemic primary. (CDSP) (OMIM 212140) A one-year-old girl with progressive dyspnea since birth and a history of parental consanguinity. Severe dilated cardiomyopathy with episodes of cardiac decompensations, hepatomegaly, anemia, generalized hypotonia, but no hypoglycemia were demonstrated prior to cardiac arrest. Extremely low carnitine level noted in dried blood spots via tandem mass spectrometry.

Carnitina, niveles en el recién nacido y su relaión con toxremia gravídica / Carnitine concentration in the newborn and its relation with gravid toxemia

Introducción. La carnitina puede ejercer efectos relevantes para la medicina obstétrica y neonatal, por lo que garantizar un aporte adecuado de ésta durante el embarazo es importante para lograr un óptimo desarrollo del feto. En virtud de que la toxemia gravídica compromete en forma importante el flujo placentario, podría estar comprometido el paso de carnitina al feto, por lo que el presente estudio fue realizado con el propósito de comparar los niveles de carnitina plasmática obtenidos en recién nacidos de madres con toxemia gravídica (toxémicas) y los recién nacidos de madres sin toxemia gravídica (controles) y establecer la posible influencia de esta enfermedad sobre estos niveles. Material y métodos. Se determinaron los niveles plasmáticos de carnitina a 100 recién nacidos y a sus respectivas madres, 50 hijos de madres toxémicas y 50 controles. La determinación de los niveles plasmáticos de carnitina se realizó por el método enzimático descrito por Marquitz y Fitz. Resultados. Se observó una diferencia significativa en los niveles plasmáticos de carnitina entre los recién nacidos de ambos grupos, siendo estos niveles menores en el grupo de toxémicas (16.16 nM/mL). No se evidenció diferencia significativa en la carnitinemia de las madres. Existe correlación entre los niveles de carnitina maternos y del recién nacido en ambos grupos, pero con coeficientes de correlación distintos. Conclusiones. La toxemia gravídica se asocia a una disminución de los niveles plasmáticos de carnitina en el recién nacido, aunque se mantiene la correlación con los niveles maternos

Evaluación nutricional en pacientes pediátricos con infección VIH / Nutritional evaluation in paediatric patients with HIV infection

Para conocer el estado nutricional de los niños chilenos infectados por VIH, se evaluaron todos aquellos en control en los Servicios de Salud de Santiago (n = 34) con infección VIH confirmada, en distintas etapas clínicas (agosto a octubre de 1996), 19 mujeres y 15 varones (0,5 a 9,0 años). Se evaluó antropometría y nutrición de zinc (Zn), cobre (Cu), retinol, tocoferol, carnitina y hierro, además de encuesta alimentaria. El estado nutricional P/E o P/T reveló a 12 desnutridos o en riesgo, sin asociación con etapa clínica. Seis tenían Zn en pelo bajo; 23 tenían Zn plasmático bajo, asociado con compromiso antropométrico (p = 0,04) y con enfermedad más avanzada (p = 0,022). Dos tenían hipocupremia, tres tocoferol bajo y todos retinol normal; 11 tenían carnitina total baja, 24 déficit de carnitina libre y 17 carnitina esterificada elevada. La ferritina sérica mostró déficit en 10 pacientes. Las encuestas revelaron ingestas normales de energía y proteína; 23 estaban bajo el 80 por ciento de las recomendaciones y riesgo de deficiencia de Zn y carnitina

L-carnitine administration in coronary artery disease and cardiomyopathy.

Myocardial ischaemia may be defined as a deficiency in cardiac energy supply relative to energy demand. In coronary artery disease (CAD), oxygen supply is limited due to coronary obstruction so energy production is not enough to meet the energy demands for work. Several reports involving about 2500 patients of CAD where carnitine was administered for upto 1 year indicate some beneficial effects. There is reduction in ischaemia showing reduced ST-segment depression and angina, greater effort tolerance and decreased need of cardiac drugs. Carnitine can cause overall improvement in cardiac performance in patients with CAD as well as in cardiomyopathy. More studies are necessary to demonstrate where carnitine can scavenge free radicals apart from its beneficial effect on fatty acid metabolism. Side effects of carnitine are mild nausea and vomiting and dose upto 2 g/day in 3 divided doses may not have any side effects. Intravenous L-carnitine acts rapidly and has no side effects.

Difteria en niños: prevención de miocarditis con carnitina oral asociado al tratamiento estandar / Children diphtheria: prevention of myocarditis using oral carnitine associated to the standard treatment

Para evaluar la eficacia preventiva de la DL-carnitina en el miocardio, se estudiaron 40 niños con difteria, internados en el Servicio de Infecto-contagiosas del Departamento de Pediatría, Hospital Belén, Trujillo-Perú entre 1986 a 1989. Veinte niños recibieron tratamiento estandar (grupo control) y los otros 20 tratamiento estandar + carnitina: 100 mg/k/d, dos dosis por día y por 4 días consecutivos. El compromiso miocárdico se determinó por la clínica, ECG, niveles de TSGO > 60 UK/ml (29 UI) y el promedio en días de estancia hospitalaria. Miocarditis se presentó en 75 por ciento del grupo control (sin carnitina) y en 30 por ciento del grupo experimental (con carnitina), p < 0.01; la estancia hospitalaria fue de 17.5 días en el primero y 10.8 en el segundo, p < 0.005; mientras por gravedad de miocarditis no fue significativo en ambos grupos. Se concluye, que la DL-carnitina oral asociado al tratamiento estandar de la difteria en niños, tiene efecto preventivo de miocarditis

Alteraçoes oteneurológicas em deficiência sistêmica de carnitina: relato de um caso / Otoneurologic alteration in carnitine deficiency: report of case

Mitochondrial disorders can be caused by carnitine deficiency. Carnitine is a cofactor in the transport of long-chain free fatty acids into mitochondria, weher they will be metabolized in order to produce energy for the cell. Patients with carnitine deficiency generally present episodes of intensive vomiting, progressive musuclar weaknes, encephalopathy and metabolic acidosis. We report a case of a 5-year-old patient, female, whose twin sister died or recurrent episodes of intense vomiting. The patient presented intense vomiting, loss of balance, dehydratation and progressive muscular weakness. Seh also presented vertigo (irritative vestibular syndrome) and a moderate sensorineural hearing loss with a good vocal discrination. In the inner ear, the stria vascularis is a highly vasculari structure with a great mitochondrial concentration, and it is necessary to keep a high level of potassium in the endolymph. When there is not a sufficient supply of glucose, the fatty acid are used in order to produce energy. This is how patients with carnitine deficiency can eventually present labyrinthine disorders

Deficiência muscular de carnitina: relato de 8 casos com estudo clínico, eletromiográfico, histoquímico e bioquímico muscular / Muscle carnitive defeciency: report of 8 cases with clinical eletromyographic, histochemical biochemical study

Säo relatados os casos de 8 pacientes, sendo 7 do sexo masculino, cuja idade variou entre 5 dias e 64 anos. Sete pacientes apresentavam diminuçäo da força muscular e todos apresentavam, nas biópsias musculares, acúmulo de lipídios. Os síntomas iniciaram nos primeiros dias de vida em três pacientes, na infância em dois, na idade adulta em dois; um dos casos apresentava-se assintomático aos 64 anos de idade (heterozigoto?). Em graus variáveis os pacientes apresentavam dificuldades na deglutiçäo, atrofia muscular, dificuldades na mastigaçäo, parestesias em membros inferiores, hepatomegalia e esplenomegalia. Cinco casos tinham história familiar e um relatava recorrências dos sintomas. Todos apresentavam aumento dos enzimas séricos, principalmente da creatinoquinase. A eletromiografia foi compatível a envolvimento muscular primário em um caso, desenervaçäo em dois neuromiopático em dois, näo tendo sído realizada em três casos. Na biópsia muscular, em todos os casos, além do acúmulo de lipídios, ocorriam: componente de desenervaçäo em 4, miopatia crônica em 4, atrofia de fibras do tipo II em um. Em dois casos, as alteraçöes histológicas eram sugestivas de atrofia espinhal infantil. Um dos casos, possivelmente pertencente à forma sistêmica de deficiência de carnitina, possuia importante envolvimento miocárdio, vindo a falecer. Säo discutidos aspectos clínicos, metabólicos e terapêuticos da deficiências musculares de carnitina