Biomedical subjects

C Stromberger

Publications and source records attributed to C Stromberger.

7 recordsLinked to original sources

PubMed2005

Pipecolic acid concentrations in brain tissue of nutritionally pyridoxine-deficient rats.

Elevated concentrations of pipecolic acid have been reported in plasma and CSF of patients with pyridoxine-dependent epilepsy, but its molecular background is unclear. To investigate any further association of pyridoxine and pipecolic acid metabolism, we have performed an animal trial and have measured the concentration of pipecolic acid in brain tissue of rats with nutritional pyridoxine deficiency and in control littermates. Concentrations of pyridoxal phosphate were significantly reduced in brain tissue of pyridoxine-deficient rats (p < 0.001), while concentrations of pipecolic acid were not significantly different from the normally nourished control group (p = 0.3). These data indicate that a direct association of pyridoxine and pipecolic acid metabolism is unlikely. We therefore assume that the characteristic elevation of pipecolic acid in pyridoxine-dependent epilepsy could rather be a secondary phenomenon with the primary defect of pyridoxine-dependent epilepsy being located outside the pipecolic acid pathway.

Animal Nutritional Physiological Phenomena↗

PubMed2004

Characterization of seven novel mutations in seven patients with GAMT deficiency.

Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive error of creatine synthesis characterized by cerebral creatine deficiency, accumulation of guanidinoacetate, mental retardation, epilepsy and extrapyramidal signs. So far, six mutations have been identified in seven patients. We investigated seven new patients by screening the promoter, 3'UTR, and six exons and exon/intron boundaries using direct sequencing and denaturing gradient gel electrophoresis. The clinical and biochemical phenotype was characterized by scoring the degree of main clinical manifestations and by determination of urinary guanidinoacetate concentrations and of GAMT activity in fibroblasts / lymphoblasts, respectively. We identified 7 novel mutations, including c.64dupG (exon 1; 4/14 alleles); c.59G>C (exon 1; 3/14 alleles); c.491delG (exon 5; 2/14 alleles); c.160G>C (exon 1; 2/14 alleles); and c.152A>C (exon 1; 1/14 alleles); c.526dupG (exon 5; 1/14 alleles); c.521G>A (exon 5; 1/14 alleles), and two polymorphisms c.626C>T (exon 6) and c.459+71G>A (intron 4). Frameshift and missense mutations in exon 1 were prevalent in the 4 patients with the severe phenotype, however a clear genotype-phenotype correlation has not been established in the limited number of patients characterized so far.

Adolescent↗

PubMed2004

Fabry disease defined.

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Dosage Compensation, Genetic↗

PubMed2003

Clinical characteristics and diagnostic clues in inborn errors of creatine metabolism.

Creatine deficiency syndromes are a newly described group of inborn errors of creatine synthesis (arginine:glycine amidinotransferase (AGAT) deficiency and guanidinoaceteate methyltransferase (GAMT) deficiency) and creatine transport (creatine transporter (CRTR) deficiency). The common clinical denominator of creatine deficiency syndromes is mental retardation and epilepsy, suggesting the main involvement of cerebral grey matter (grey matter disease). Patients with GAMT deficiency exhibit a more complex clinical phenotype with dystonic hyperkinetic movement disorder and epilepsy that in some cases is unresponsive to pharmacological treatment. The common biochemical denominator of creatine deficiency syndromes is cerebral creatine deficiency which is demonstrated by in vivo proton magnetic resonance spectroscopy. Measurement of guanidinoacetate in body fluids may discriminate GAMT (high concentration), AGAT (low concentration) and CRTR (normal concentration). Further biochemical characteristics include changes in creatine and creatinine concentrations in body fluids. GAMT and AGAT deficiency are treatable by oral creatine supplementation, while patients with CRTR deficiency do not respond to this type of treatment. Further recognition of patients will be of major importance for the estimation of the frequency, for the understanding of phenotypic variations and for treatment strategies.

Creatine↗

PubMed2002

Effects of oral creatine supplementation in a patient with MELAS phenotype and associated nephropathy.

An 18-year-old male patient with MELAS phenotype and 2 previous episodes of cerebral stroke, recurrent seizures and nephropathy, was treated with creatine monohydrate after the acute onset of psychomental regression and changing states of somnolence and aggressive and agitated behaviour. These symptoms disappeared completely after 4 weeks of treatment with creatine after which the patient regained all his previous mental abilites. Brain (white matter) proton magnetic resonance spectroscopy (chemical shift imaging) performed at 6 and 12 months of treatment showed lactic acid (Lac) accumulation and high creatine (Cr) levels in relation to choline-containing compounds (Cho). Urinary creatinine excretion as an indicator of the muscle and brain creatine pool increased upon short-term (12 days) high-dosage creatine supplementation (20 g per day) while plasma creatinine concentrations as possible indicators both of increasing creatine pool and of renal insufficiency increased during the course (28 months) of low-dosage creatine supplementation (5 g per day). Deterioration of renal function was finally indicated by urea retention and by impairment of renal creatinine clearance. These observations suggest that creatine supplementation may have a neuroprotective effect in patients with MELAS and episodes of acute mental deterioration. Adverse effects of creatine supplementation on renal function must be considered especially in patients with preexisting nephropathy.

Administration, Oral↗

PubMed2001

Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans.

Arginine:glycine amidinotransferase (AGAT) catalyzes the first step of creatine synthesis, resulting in the formation of guanidinoacetate, which is a substrate for creatine formation. In two female siblings with mental retardation who had brain creatine deficiency that was reversible by means of oral creatine supplementation and had low urinary guanidinoacetate concentrations, AGAT deficiency was identified as a new genetic defect in creatine metabolism. A homozygous G-A transition at nucleotide position 9297, converting a tryptophan codon (TGG) to a stop codon (TAG) at residue 149 (T149X), resulted in undetectable cDNA, as investigated by reverse-transcription PCR, as well as in undetectable AGAT activity, as investigated radiochemically in cultivated skin fibroblasts and in virus-transformed lymphoblasts of the patients. The parents were heterozygous for the mutant allele, with intermediate residual AGAT activities. Recognition and treatment with oral creatine supplements may prevent neurological sequelae in affected patients.

Amidinotransferases↗

PubMed2001

Changes of tissue creatine concentrations upon oral supplementation of creatine-monohydrate in various animal species.

Creatine is a nutritional supplement with major application as ergogenic and neuroprotective substrate. Varying supplementation protocols differing in dosage and duration have been applied but systematic studies of total creatine (creatine and phosphocreatine) content in the various organs of interest are lacking. We investigated changes of total creatine concentrations in brain, muscle, heart, kidney, liver, lung and venous/portal plasma of guinea pigs, mice and rats in response to 2-8 weeks oral creatine-monohydrate supplementation (1.3-2 g/kg/d; 1.4-2.8% of dietary intake). Analysis of creatine and phosphocreatine content was performed by high performance liquid chromatography. Total creatine was determined as the sum of creatine and phosphocreatine. Presupplementation total creatine concentrations were high in brain, skeletal and heart muscle (10-22 micromol/g wet weight), and low in liver, kidney and lung (5-8 micromol/g wet weight). During creatine supplementation, the relative increase of total creatine was low (15-55% of presupplementation values) in organs with high presupplementation concentrations, and high (260-500% of presupplementation values) in organs with low presupplementation concentrations. The increase of total creatine concentrations was most pronounced after 4 weeks of supplementation. In muscle, brain, kidney and lungs, an additional increase (p<0.01) was observed between 2-4 and 2-8 weeks of supplementation. Absolute concentrations of phosphocreatine increased, but there was no increase of the relative (percentual) proportion of phosphocreatine (14-45%) during supplementation. Statistical comparison of total creatine concentrations across the species revealed no systematically differences in organ distribution and in time points of supplementation. Results suggest that in organs with low presupplementation creatine levels (liver, kidney), a major determinant of creatine uptake is an extra-intracellular concentration gradient. In organs with high presupplementation total creatine levels like brain, skeletal and heart muscle, the maximum capacity of creatine accumulation is low compared to other organs. A supplementation period of 2 to 4 weeks is necessary for significant augmentation of the creatine pool in these organs.

Administration, Oral↗