Symptoms Of Carnitine Deficiency Research Articles

Carnitine status before and after paracentesis in patients with ascites and liver cirrhosis and improvement of subjective symptoms by intravenous administration of carnitine ― Initial study

Carnitine status before and after paracentesis in patients with ascites and liver cirrhosis and improvement of subjective symptoms by intravenous administration of carnitine ― Initial study

Gestational diabetes exhibits lack of carnitine deficiency despite relatively low carnitine levels and alterations in ketogenesis

Objective: Previous studies have underlined the importance of the carnitine shuttle system and its dysfunction both in normal pregnancy and in type 1 and 2 diabetes. The objective of this paper was to delineate more systematically the role of the carnitine shuttle system in normal pregnancy and in gestational diabetes.Methods: A total of 119 women matched for age comprised three groups: 40 normal adult non-pregnant women (NNP), 46 normal pregnant women with uncomplicated pregnancy (NP) and 33 women with gestational diabetes (GDM). The latter group was further subdivided into those being managed either by diet alone (25 women, GDM-D) or by insulin (8 women, GDM-I). The following biochemical parameters were assayed: fasting plasma total, free and acyl-carnitine, FFA and β-OH-butyrate, together with several essential anthropometric parameters.Results: Women with GDM, in contrast to the control groups, displayed the biochemical features characteristic of insulin resistance: higher body weight, higher BMI, higher skinfold and higher HbA1c levels. No differences on any parameters were found between the two GDM subgroups. Both NP and GDM groups had low levels of total carnitine compared to NNP control group, but surprisingly, the GDM group did not exhibit any further decrease of carnitine levels, as would have been expected by the combination of pregnancy and diabetes. Both groups, despite these low carnitine levels, had no clinical symptoms of carnitine deficiency. Furthermore, the GDM group displayed higher levels of FFA and β-hydroxybutyrate, which were statistically significant compared to the other two control groups.Conclusions: The data corroborate the negative effect of normal gestation on the carnitine shuttle system, while they document for the first time that GDM does not further affect the efficiency of the carnitine system. The mild effect of GDM on carnitine status could be explained by the concurrent increased gluconeogenesis, a process which does not affect directly carnitine metabolism.

Carnitine membrane transporter deficiency: a long-term follow up and OCTN2 mutation in the first documented case of primary carnitine deficiency

Three older patients were diagnosed with systemic carnitine deficiency in childhood nearly a generation ago and have together been treated for more than 50 patient years. Treatment improved tissue carnitine stores (proven in two) and eliminated most of the signs and symptoms of carnitine deficiency. All three have continued to respond to carnitine therapy and remain well except for the irreversible sequelae of the pretreatment illnesses. We demonstrate here that transformed lymphocytes from the first documented case of plasma membrane carnitine transporter deficiency fail to take up carnitine from the medium. The analysis of the cDNA of this patient and his parents revealed a homozygous frameshift mutation, 1027delT in exon 4. The resulting polypeptide terminates after amino acid 295. His parents are heterozygous for this mutation. The deletion resulted in predominately abnormal mRNA splicing with either a 13 or 19 bp insertion between the junction of exons 3 and 4. The 13/19 bp insertions were found in both parents, predominantly in cis with the deletion, and rarely seen with normal alleles from either parents or controls.

A Review of Valproic Acid–Induced Carnitine Deficiency and Replacement

Objective: To review valproic acid–induced carnitine deficiency and subsequent carnitine replacement. Data Sources: Articles indexed in MEDLINE from 1966 to May 2000, as well as other published works and standard references. Data Extraction: Studies investigating clinical epidemiologic and pathologic evidence of the role of valproic acid–induced carnitine deficiency and double-blind clinical trials evaluating the effectiveness of carnitine replacement with anticonvulsant therapy are presented. Data Synthesis: Clinical epidemiologic and pathologic studies provide evidence of valproic acid–induced carnitine deficiency. There is no clear consensus for providing carnitine supplementation to all patients taking valproic acid — It is only indicated for children with valproic acid–induced hepatotoxicity and those with valproic acid overdose. Conclusions: There is evidence that implicates valproic acid in inducing carnitine deficiency. Patients should be evaluated clinically for signs and symptoms of carnitine deficiency before beginning supplementation. Currently, carnitine supplementation should be reserved for children with valproic acid–induced hepatotoxicity and valproic acid overdose until the results of further clinical studies are available.

Cefetamet Pivoxil

Cefetamet pivoxil is an oral third-generation cephalosporin which is hydrolysed to form the active agent, cefetamet. Cefetamet has excellent in vitro activity against the major respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and group A beta-haemolytic streptococci; it is active against beta-lactamase-producing strains of H. influenzae and M. catarrhalis, but has poor activity against penicillin-resistant S. pneumoniae. Cefetamet has marked activity against Neisseria gonorrhoeae and possesses a broad spectrum of activity against Enterobacteriaceae. Both staphylococci and Pseudomonas spp. are resistant to cefetamet. Cefetamet pivoxil has been investigated in the treatment of both upper and lower community-acquired respiratory tract infections and has demonstrated equivalent efficacy to a number of more established agents, namely cefaclor, amoxicillin and cefixime. In patients with group A beta-haemolytic streptococcal pharyngotonsillitis, a 7-day course of cefetamet pivoxil was as effective as a 10-day course of the standard agent, phenoxymethylpenicillin, in this indication. In complicated urinary tract infections, cefetamet pivoxil showed similar efficacy to cefadroxil, cefaclor and cefuroxime axetil. Cefetamet pivoxil was effective in the treatment of otitis media, pneumonia, pharyngotonsillitis and urinary tract infections in children. Preliminary data indicate that single dose cefetamet pivoxil can effectively eradicate N. gonorrhoeae from both men and women. Cefetamet pivoxil has a tolerability profile similar to that of other oral cephalosporins, with gastrointestinal effects being the most commonly reported adverse events. To date, no symptoms of carnitine deficiency have been reported with cefetamet pivoxil. Cefetamet pivoxil offers effective alternative oral therapy for outpatient treatment of community-acquired respiratory tract infections, with the advantage of improved activity against H. influenzae and increased beta-lactamase stability. However, its use in areas with a high incidence of penicillin-resistant S. pneumoniae is likely to be limited. Cefetamet pivoxil is also effective in the treatment of urinary tract infections, although further trials are required to define any comparative advantages over other oral agents.

Secondary Carnitine Deficiency in Handicapped Patients Receiving Valproic Acid and/or Elemental Diet

We examined serum-free carnitine (SFC) concentrations and serum acylcarnitine (SAC)/SFC ratios in 40 severely handicapped patients, aged 2 to 36 years, and 69 age-matched control subjects. SFC levels in the patients treated with valproic acid (VPA) and/or receiving carnitine-deficient elemental diets (ED) were significantly lower, and their SAC/SFC ratios were significantly higher than in the other patients or in control subjects. There were 6 patients whose SFC levels were less than the -2SD level (15.8 +/- 6.7 microM, range 6.3-25.5) of those in control subjects (52.1 +/- 11.5 microM). They had no clinical symptoms of carnitine deficiency such as non-ketotic hypoglycemia, hepatomegaly, muscle weakness or cardiac function impairment, and showed normal transaminase, lipid and ammonia levels. In two cases (SFC = 11.0, 13.4 microM), the ketogenic responses to intravenous administration of fat-emulsion were impaired, but they were restored after D-,L-carnitine supplementation (30 mg/kg/day, po) for 1 month. However, in one case with the lowest SFC level (6.3 microM), the ketogenic responses to fat-emulsion infusion or fasting were normal, and dicarboxylic aciduria was not detected. These results indicate that 1) SFC levels are reduced in handicapped patients receiving VPA and/or ED, although clinical symptoms of carnitine deficiency do not easily develop, 2) some of these hypocarnitinemic cases show a subclinical impairment of hepatic fatty acid metabolism, not always correlated with the degree of SFC reduction, which can be restored by exogenous carnitine supplements, and therefore 3) in patients with acquired hypocarnitinemia, carnitine therapy should be considered, although a low SFC level alone may not imply an immediate indication.