Search PubMed⌕ Search

Biomedical subjects

E Mayatepek

Publications and source records attributed to E Mayatepek.

At least 109 records · Page 6Linked to original sources
PubMed1997

Creatine deficiency syndrome caused by guanidinoacetate methyltransferase deficiency: diagnostic tools for a new inborn error of metabolism.

Hepatic guanidinoacetate methyltransferase deficiency induces a deficiency of creatine/phosphocreatine in muscle and brain and an accumulation of guanidinoacetic acid (GAA), the precursor of creatine. We describe a patient with this defect, a 4-year-old girl with a dystonic-dyskinetic syndrome in addition to developmental delay and therapy-resistant epilepsy. Several methods were used in the diagnosis of the disease: (1) the creatinine excretion in 24-hour urine was significantly lowered, whereas the creatinine concentration in plasma and in randomly collected urine was not strikingly different from control values; (2) the Sakaguchi staining reaction of guanidino compounds in random urine samples indicated an enhanced GAA excretion; (3) GAA excretion measured quantitatively by guanidino compound analysis using an amino acid analyzer was markedly elevated in random urine samples; (4) in vivo 1H magnetic resonance spectroscopy (MRS) revealed a strong depletion of creatine and an accumulation of GAA in brain; (5) in vivo phosphorus 31 MRS showed a strong decrease of the phosphocreatine resonance and a resonance identified as guanidinoacetate phosphate; and (6) in vitro 1H MRS showed an absence of creatine and creatinine resonances in cerebrospinal fluid and the occurrence of GAA in urine. For early detection of this disease, we recommend the Sakaguchi staining reaction of urine from patients with dystonic-dyskinetic syndrome, seizures, and psychomotor retardation. Positive results should result in further investigations including quantitative guanidino compound analysis and both in vivo and in vitro MRS. Although epilepsy was not affected by orally administered creatine (400 to 500 mg/kg per day), this treatment resulted in clinical improvement and an increase of creatine in cerebrospinal fluid and brain tissue.

Amino Acid Metabolism, Inborn Errors↗
PubMed1997

Influence of n-6 and n-3 polyunsaturated fatty acids on the resistance to experimental tuberculosis.

It has previously been shown that the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (20:5(n-3)) and docosahexaenoic acid (22:6(n-3)) possess antiinflammatory properties and can interfere with immune functions. To evaluate whether this would affect resistance to infection, we studied the influence of different types of fatty acids (FAs) on experimental tuberculosis in an animal model. Three groups of 26 weanling guinea pigs were fed isocaloric diets with 26 cal% fat that differed in FA composition with respect to saturated FAs, linoleic acid (18:2(n-6)), eicosapentaenoic acid (20:5(n-3)), and docosanexaenoic acid (22:6(n-3)) as follows: (1) reference (REF) group: 14.8 cal% saturated FAs and 2.8 cal% linoleic acid; (2) n-6 group: 4.6 cal% saturated FAs and 15.4 cal% linoleic acid; (3) n-3 group: 6.3 cal% saturated FAs, 10 cal% linoleic acid, 1.4 cal% eicosapentaenoic acid, and 0.9 cal% docosahexaenoic acid. After 13 weeks, 18 animals from each group were intramuscularly injected with 180 colony-forming units (CFU) Mycobacterium tuberculosis strain H37Rv. Eight noninfected animals per group served as controls. Seven weeks later, the mean number of mycobacteria recovered from the spleens of the n-3 group (log 4.34 CFU, standard error of the mean [SEM], 0.12) was significantly higher than from the REF group (log 3.90 CFU; SEM, 0.15) and the n-8 group (log 3.93 CFU; SEM, 0.13; P < .05). In addition, the Root Index of Virulence (RIV) showed the most pronounced progression of the disease in the n-3 group. The mean size of the tuberculin reaction was larger in the n-3 group than in the other groups (P < .05). There was no significant difference between the n-6 group and the REF group. We conclude that supplementing the diet with n-3 FAs eicosapentaenoic acid and docosahexaenoic acid can affect resistance to M tuberculosis, whereas supplementing with n-6 FAs does not.

Animals↗
PubMed1997

Effect of plasma alpha-tocopherol on leukotriene E4 excretion in genetic vitamin E deficiency.

Studying the biological effects of vitamin e in humans is difficult because conditions involving vitamin E deficiency are usually associated with chronic multiple pathology. Genetic vitamin E deficiency caused by a deficient alpha-tocopherol transport protein offers unique possibilities for study of vitamin E effects since the patients can be studied in good general health. In such a patient we manipulated plasma alpha-tocopherol levels in a wide range by varying oral alpha-tocopherol supplements and measured urinary leukotriene E4 (LTE4) concentrations. LTE4 excretion proved inversely correlated to plasma alpha-tocopherol levels. This strongly suggests that in genetic vitamin E deficiency, alpha-tocopherol influences formation of leukotrienes in vivo.

Adolescent↗
PubMed1997

Continuous mannose infusion in carbohydrate-deficient glycoprotein syndrome type I.

The effects on isoelectrofocusing patterns of serum glycoproteins were studied in a patient with CDG syndrome type I and phosphomannomutase deficiency during 3 weeks of continuous intravenous mannose infusion. Doses of 5.7 g/kg/day led to stable serum mannose levels up to 2.0 mmol/l and were well tolerated without signs of liver or renal toxicity. While most of the pathological glycoprotein patterns, including alpha1-antitrypsin, typical for CDG syndrome type I remained unchanged, mannose infusion led to a unique change of the isoelectrofocusing pattern of serum sialotransferrins with appearance of two extra bands after 3 weeks of treatment.

Acyl Carrier Protein↗
PubMed1997

Early clinical manifestation of glutaric aciduria type I and nephrotic syndrome during the first months of life.

We describe a male patient with glutaric aciduria type I which had already presented during the neonatal period with therapy-resistant seizures. In the course of the disease, he also developed choreoathetosis and dystonia. The disease was associated with nephrotic syndrome. Renal histology showed signs of a glomerular disorder with shrinking of glomerular tufts, increase in mesangial matrix, proliferation of extracapillary epithelial cells and formation of larger epithelial crescents. The child died at 22 weeks of age due to end-stage renal failure. This report illustrates an unusual and early clinical manifestation of glutaric aciduria type I and a hitherto unknown association with nephrotic syndrome in early childhood.

Fatal Outcome↗
PubMed1996

Defective degradation of leukotrienes in peroxisomal-deficient human hepatocytes.

Chain-shortening via beta-oxidation from the omega-end has been recognized as the major pathway for the degradation of the biologically active cysteinyl leukotrienes as well as LTB4. The metabolic compartmentation of this pathway was investigated in peroxisomal-deficient (Zellweger syndrome) and normal human hepatocytes. Leukotriene metabolism was studied in isolated hepatocytes by incubation with omega-carboxy-[3H]LTE4 as well as omega-carboxy-[3H]LTB4. Analysis was done by HPLC, UV-detection and radioactivity measurements. Incubation of normal hepatocytes with omega-carboxy-[3H]LTE4 or omega-carboxy-[3H]LTB4 resulted in the formation of the corresponding beta-oxidation products, whereas beta-oxidation derivatives were not detected as products formed by peroxisome-deficient human hepatocytes. These results underline the essential contribution of peroxisomes in the catabolism and inactivation of cysteinyl leukotrienes and LTB4 in humans.

Humans↗
PubMed1996

Defective hepatobiliary leukotriene elimination in patients with the Dubin-Johnson syndrome.

The Dubin-Johnson syndrome (DJS) is characterized by a hereditary conjugated hyperbilirubinemia and a typical dark pigment accumulation in liver parenchymal cells. In the present study the renal excretion of leukotrienes in five patients with histologically established DJS and five age- and sex-matched healthy subjects was investigated. Endogenous urinary leukotrienes were separated by high-performance liquid chromatography and subsequently quantified by immunoassays and gas chromatography-mass spectrometry. Patients with DJS excreted significantly (P < 0.01) greater amounts of cysteinyl leukotriene, LTE4 (8-fold), the omega-oxidation product omega-carboxy-LTE4 (15-fold) and the beta-oxidation metabolite omega-carboxy-tetranor-LTE3 (26-fold) into urine than healthy controls. These results imply that in DJS leukotriene elimination into bile is defective, leading to a compensatory renal leukotriene elimination and a typical excretion pattern of urinary leukotriene metabolites. Analysis of endogenous urinary leukotrienes seems to be a new approach to the noninvasive diagnosis of this disease.

Adult↗
PubMed1996

Atypical vitamin B12-unresponsive methylmalonic aciduria in sibship with severe progressive encephalomyelopathy: a new genetic disease?

UNLABELLED: We report on two siblings, a girl of 7 years and a boy of 2 years, who presented in infancy with hypotonia, athetoid movements, myopathy and severe developmental delay. The progressive clinical course was characterized by ophthalmoplegia, pyramidal tract signs, loss of visual contact and failure to thrive. The older sister died at the age of 7 years. The younger brother followed an almost identical clinical course. MRI of the brain revealed bilateral hypodensities and atrophy of the putamen. Neurophysiological investigations were consistent with peripheral neuropathy. Investigations for neurometabolic disorders in urine, plasma and CSF of both patients revealed a consistent increase of methylmalonic acid in urine, plasma and CSF as well as borderline low free GABA in CSF. Except for an inconstant elevation of lactate in the boy, metabolic acidosis, hypoglycaemia, episodic ketoacidosis, or hyperammonaemia, the usual concomitants of organoacidopathies, were absent in both children. Homocystinuria was excluded. Methylmalonic aciduria did not respond to antibiotic treatment, vitamin B12 therapy nor dietary protein restriction. Incorporation of [14C]propionate into protein in cultured fibroblasts was pathologically but inconsistently decreased. Both patients' cell lines showed only minimal response to hydroxocobalamin and normal methylmalonyl-CoA mutase activity. CONCLUSION: Even though the definitive underlying enzymatic defect in this sibship remains obscure our results suggest a new genetic disorder. This report illustrates that hitherto undescribed metabolic disorders remain to be elucidated even in long investigated areas of intermediary metabolism such as methylmalonic aciduria.

Amino Acid Metabolism, Inborn Errors↗
PubMed1996

Severe hyperchloriduria-hyperkaliuria: a new congenital renal tubular abnormality?

A female infant, aged 5 weeks, had metabolic alkalosis associated with severe electrolyte disturbances. In addition to findings typically seen in patients with Bartter syndrome or hyperprostaglandin E syndrome, she had massive urinary excretion of prostaglandins E2 and E-M, normal calcium metabolism, hyperphosphaturia, and severe hyperchloriduria and hyperkaliuria with limited response to indomethacin. These findings may represent a new congenital renal tubular abnormality.

Bartter Syndrome↗
PubMed1996

12- and 15-hydroxyeicosatetraenoic acid are excreted in the urine of peroxisome-deficient patients: evidence for peroxisomal metabolism in vivo.

To determine the importance of peroxisomes and mitochondria in hydroxyeicosatetraenoic acid (HETE) oxidation in vivo, urinary excretion of 12- and 15-HETE was measured in eight patients with a peroxisome deficiency disorder (Zellweger syndrome) showing normal mitochondrial beta-oxidation capacity, in three patients with a defect of mitochondrial long-chain fatty acid oxidation (long-chain acyl-CoA dehydrogenase deficiency), and in eight healthy subjects. 12- and 15-HETE were identified and quantified by gas chromatography/negative ion chemical ionization-mass spectrometry and specific RIA. The free compounds were found exclusively in the urine of peroxisome-deficient subjects (12-HETE: median 26 pg/mL, range 17-36 pg/mL; 15-HETE: median 40 pg/mL, range 29-61 pg/mL), whereas both compounds were below the detection limit (< 0.5 pg/mL) in the urine of patients with defective mitochondrial long-chain fatty acid oxidation and normal subjects (p < 0.002). These results implicate that peroxisomes are the main cellular organelle responsible for HETE oxidation in vivo. Analysis of HETE excretion in urine represents an additional new specific diagnostic tool in patients with Zellweger syndrome.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗