Hyperketonaemia in glycerol kinase deficiency.
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Child, Preschool↗
Biomedical subjects
W Sperl
Publications and source records attributed to W Sperl.
Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study.
The decrease in intracellular creatine concentration in Duchenne muscular dystrophy may contribute to the deterioration of intracellular energy homeostasis and may thus be one of the factors aggravating muscle weakness and degeneration. Oral creatine supplementation should have potential in alleviating the clinical symptoms. To test this hypothesis, creatine was orally administered over a period of 155 days to a 9-year-old patient with Duchenne muscular dystrophy. In accordance with previous investigations on normal subjects and trained athletes, the patient experienced improved muscle performance during creatine supplementation. Further evidence supporting this hypothesis derived from plasma creatine kinase and lactate dehydrogenase activities and repeated 31P magnetic resonance spectroscopy of the gastrocnemius muscle. These preliminary observations indicate a potential role for creatine supplementation in the symptomatic therapy of patients with muscle disease.
Administration, Oral↗
Lactobacilli and acidosis in children with short small bowel.
BACKGROUND: In patients with a short small bowel, D-lactic acidemia and D-lactic aciduria are caused by intestinal lactobacilli. The purpose of this study was to obtain a detailed picture of the metabolic acidosis in young children with short small bowel. METHODS: Feces, blood, and urine of children with short small bowel and acidosis were studied microbiologically and/or biochemically. RESULTS: Previous findings were confirmed that more than 60% of the fecal flora of patients with small short bowel, who are not receiving antibiotics, consists of lactic acid-producing lactobacilli. In blood, D-lactic acid was the most prominent metabolite: the highest serum D-lactate (15.5 mmol/l) was observed in a sample taken immediately after the onset of hyperventilation. The highest D-lactate excretion was in urine collected some hours after the onset of hyperventilation, and amounted to 59 mol/mol creatinine. Acidosis in the patients with short small bowel was related to strongly increased serum D-lactate and anion gap and to strongly decreased serum bicarbonate and pH. CONCLUSION: In children with small short bowel and acidosis, the common intestinal flora of mainly lactobacilli abundantly produces D-lactic acid from easily fermentable carbohydrates. Thus, these bacteria directly cause shifts of bicarbonate, pH, and base excess and indirectly cause shifts of the anion gap, as well as hyperventilation. These kinetic parameters are strongly associated.
Acidosis↗
Spectrum of CFTR mutations in the Middle North of Spain and identification of a novel mutation (1341G-->A). Mutation in brief no. 252. Online.
We have analyzed 39 unrelated cystic fibrosis (CF) families by denaturing gradient gel electrophoresis (DGGE) and direct sequencing in order to determine the spectrum of CF mutations in our population. This approach has allowed us to detect 72 out of the 78 CF chromosomes (92.3%). The DF508 mutation was found to be present in 51/78 (65.4%) CF chromosomes, in accordance with the predicted Northwest-Southeast gradient within the European population. Another 14 known mutations, and the novel 1341G-->A mutation were identified. Nine out of fifteen non DF508 mutations were present in a single chromosome. The 1341G-->A mutation, found in 2 unrelated patients, is a new mutation associated to severe phenotype, causing pancreatic insufficiency and chronic lung infections. Our data suggest a different distribution of non-DF508 mutations in our population when compared with previous studies carried out in Spanish CF families. Six out of the 14 non-F508 in our study were not present in a recent study carried out in 640 Spanish families with CE These six mutations account for 29.6% non DF508 chromosomes in our sample.
Cystic Fibrosis↗
Gram type-specific broad-range PCR amplification for rapid detection of 62 pathogenic bacteria.
Broad-range PCR has proven to be useful for the detection of bacteria. A set of broad-range PCR primers directed against conserved regions in the 16S rRNA gene was designed to specifically amplify either gram-positive or gram-negative bacteria. The gram type-specific broad-range PCR correctly classified all 62 pathogenic species tested.
DNA Primers↗
Galanin and galanin receptor expression in neuroblastoma.
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Brain Neoplasms↗
Sudden infant death syndrome: risk factor profiles for distinct subgroups.
The authors investigated risk profiles of sudden infant death syndrome (SIDS) as a function of age at death. A case-control study carried out in the Tyrol region of Austria enrolled 99 infants who died of SIDS between 1984 and 1994 and 136 randomly selected controls. Early and late SIDS (< 120 days of age vs. > or = 120 days) were defined according to the clear-cut bimodal age-at-death distribution. Inadequate antenatal care, low parental social and educational level, and the prone sleeping position were risk conditions that applied to both early and late SIDS. A marked seasonal variation (winter preponderance) was the most outstanding feature of late SIDS. A gestational age of < 37 weeks (odds ratio (OR) = 8.4, 95% confidence interval (CI) 2.6-26.0), repeated episodes of apnea (OR = 5.7, 95% CI 1.2-27.0), low birth weight (< 2,500 g) (OR = 3.4, 95% CI 1.1-11.0), a family history of sudden infant death (OR = 2.9, 95% CI 1.1-7.5), and maternal smoking during pregnancy (OR = 2.2, 95% CI 1.0-4.5) were associated with early SIDS. This study identified two distinct subgroups of SIDS infants characterized by different risk conditions and ages at death. These results underline a multiple-cause hypothesis for SIDS etiology which involves a genetic predisposition, immaturity in the first months of life, and environmental factors acting at various ages.
Adult↗
The therapeutic potential of oral creatine supplementation in muscle disease.
The decrease in intracellular creatine concentration observed in a number of muscle diseases may deplete energy homeostasis and may, therefore, be one of the factors determining and/or aggravating muscle weakness and degeneration. Two hypotheses are put forward in the present communication to explain: (i) the mechanisms leading to the disturbances in creatine metabolism found in various muscle diseases; and (ii) the potential of oral creatine supplementation in alleviating the clinical symptoms.
Animals↗
Living at high altitude and risk of sudden infant death syndrome.
OBJECTIVE: To investigate the association between altitude of residence and risk of sudden infant death syndrome (SIDS). METHODS: A retrospective, case control study in the Tyrol, Austria enrolled 99 infants with SIDS occurring between 1984 and 1994, and 136 randomly selected control cases. Data on pregnancy, delivery, child care practice, and socio-demographic characteristics including altitude of residence were collected with a standardised questionnaire. RESULTS: The risk of SIDS increased gradually with increasing altitude of residence. This relation remained independently significant when the analysis was adjusted for gestational age, birth weight, prenatal care, mother's age at delivery, educational level of parents, and cigarette smoking during pregnancy. The prone sleeping position emerged as an obligatory cofactor in this association. In the whole of Austria, a similar trend of association emerged between the average altitudes in the 99 political counties and the rates of SIDS. CONCLUSIONS: This study identified altitude of residence as a significant risk predictor of SIDS, primarily in combination with the prone sleeping position. Respiratory disturbances, reduced oxygen saturation, and lower temperatures at high altitude might explain this association.
Altitude↗
[Diagnosis and therapy of mitochondriopathies].
Defects of the mitochondrial energy production cab be expressed in many tissues and may lead to various types of diseases. Since defects can occur on many sites of the oxidative phosphorylation system, molecular diagnosis can be difficult. In typical mitochondrial syndromes, like MELAS- or MERRF-syndrome, diagnosis can be suspected already on clinical grounds. Lactate measured in various body fluids is still the best selective screening parameter. Loading tests, respectively ergometry is only necessary in the milder clinical forms of diseases or possibly in older children. The in vivo lactate determination e.g. In the CNS by 1H NMR spectroscopy can be helpful in evaluating prognosis. The diagnosis of a mitochondriopathy is usually confirmed enzymatically by tissue biopsies; skeletal muscle is still the tissue of the first choice because some enzyme deficiencies are not sufficiently expressed in cultured fibroblasts. If possible, intact mitochondria should be investigated polarografically along with histology and histochemistry. Finally several parts of the respiratory chain and pyruvate dehydrogenase complex are analyzed by single enzyme measurement. Also combined deficiencies have been described. Polypeptide subunits of respiratory chain complexes can be investigated by means of immunoblotting. The investigations of the mitochondrial DNA from the end of the diagnostic scale. The application of various new therapeutic agents, such as antioxidants, radical scavangers and cofactors have not come to any persuasive clinical result. But there is a number of reports about some successful treatment with coenzyme Q10, vitamin K3, vitamin C, riboflavin, thiamine, dichloroacetate and in PDHC -deficiency with ketogenic diet. Mitochondrial gene therapy appears only theoretical and speculative. Because of the enormous heterogeneity even on the DNA-level genetic counselling is reserved for some cases with exact molecular diagnosis.
Adult↗
Stridor as the major presenting symptom in riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency.
UNLABELLED: Inspiratory stridor of unknown origin was the leading clinical symptom in an 11-month-old boy. The stridor increased over a period of 4 weeks, and assisted ventilation became necessary. Selective urinary screening by gas chromatography/mass spectrometry analysis revealed excretion of ethylmalonic and 3-OH-isovaleric acid and of N-isobutyryl-, N-2-methylbutyryl-, N-isovaleryl-, N-hexanoyl- and N-suberylglycine. Neither hypoglycaemia nor metabolic acidosis were noticed. Treatment with 200 mg of riboflavin per day led to a dramatic clinical improvement with restoration of normal respiration and an increase in muscular tone within 2 months. During this period, metabolite excretion in urine completely normalized. Riboflavin-sensitive multiple acyl-CoA dehydrogenation deficiency was confirmed in cultured fibroblasts. With riboflavin supplementation, the development of the child has been favourable, with normal school attendance now at an age of 9 years. CONCLUSION: As respiratory symptoms might precede other symptoms in disorders of mitochondrial oxidation, we propose determination of urinary organic acids in all cases of unexplained laryngeal stridor.
Adipates↗
Microheterogeneity of serum glycoproteins and their liver precursors in patients with carbohydrate-deficient glycoprotein syndrome type I: apparent deficiencies in clusterin and serum amyloid P.
Serum and liver protein patterns were studied, respectively, in 5 patients (serum) and 1 patient (liver) with carbohydrate-deficient glycoprotein syndrome (CDGS) type I by high-resolution two-dimensional electrophoresis (2-DE) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The pattern of serum glycoproteins in all 5 patients presented abnormal trains of isoforms with decreased mass (delta molecular weight 3000) and all showed a cathodal shift. Two-dimensional electrophoresis and SDS-PAGE mass analysis of transferrin, alpha1 -antitrypsin, haptoglobin beta-chain, and alpha1-acid glycoprotein after neuraminidase and N-glycosidase F treatments demonstrated that the additional trains of the isoforms found in CDGS type I contain homologous species of isoforms. Some of them still showed charge differences, and all still contained glycans except for transferrin, with some unusual nonglycosylated isoforms. In addition, deficiencies in clusterin and serum amyloid P, not described so far, have been found in all 5 patients. The two-dimensional pattern of immunodetected precursors of serum proteins in liver cells from 1 patient with CDGS showed abnormal low-mass precursors and the absence of the precursors normally found in controls. These results suggest that these abnormal precursors accumulate during the early oligosaccharide processing of the nascent protein-bound oligosaccharides and that glycoprotein precursors undergo an altered intracellular transport while the post-translational processing along the normal pathway is still apparently functioning in patients with CDGS.
Amyloid↗
Cirrhosis in a child with deficiency of mitochondrial respiratory-chain succinate-cytochrome c-oxidoreductase.
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Electron Transport Complex II↗
Essential fatty acids in clinically stable children with propionic acidaemia.
Disturbances of fatty acid metabolism with accumulation of odd-chain fatty acids have been reported in propionic acidaemia (PA). It is not known whether the synthesis of long-chain polyunsaturated fatty acids (LCPUFA) is also affected. In five clinically stable children with PA (median age 8 years, range 3.5-9.5 years; median percentage fibroblast propionyl-CoA carboxylase activity 0.8, range 0.8-1.5), we determined the fatty acid composition of plasma phospholipids, triglycerides and sterol esters and compared the results with those of 18 age-matched healthy controls. Odd-numbered fatty acids were found in all samples of PA patients but in controls median values were zero. Percentage contributions of substrate (linoleic acid, C18:2 omega-6) and principal product (arachidonic acid, C20:4 omega-6) of omega-6 LCPUFA synthesis did not differ between patients and controls. Similarly, there were no differences between both groups in the substrate (alpha-linolenic acid, C18:3 omega-3) and principal product (docosahexaenoic acid, C22:6 omega-3) of omega-3 LCPUFA formation. We conclude that disturbances of fatty acid metabolism in clinically stable children with PA do not affect LCPUFA synthesis.
Amino Acid Metabolism, Inborn Errors↗
Mitochondrial respiratory chain succinate-cytochrome-c oxidoreductase deficiency and hepatic cirrhosis.
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Electron Transport↗
Metabolic stroke in carbamyl phosphate synthetase deficiency.
Stroke-like episodes with hemiparesis have been described in children with different inherited metabolic diseases. We report the novel observation of a severe stroke as the presenting sign in an 18-month-old girl with carbamyl phosphate synthetase (CPS) deficiency. MRI revealed infarction within the territory of the right middle cerebral artery. Localized 1H-NMR spectroscopy showed elevation of glutamine (at 2.0-2.5 and 3.7 ppm) and lactate within the region of infarction. CPS activity in the liver was reduced (2.5 mU/ mg protein, n = 12-35). On a protein-restricted diet including arginine supplementation, the child has developed well with moderate mental retardation: no neurologic relapses have been observed over a period of 4 years. CPS deficiency has to be added to the list of metabolic diseases that may lead to stroke-like episodes. In every case of unclear hemiparesis in childhood, urea cycle defects should be included in the differential diagnosis.
Ammonia↗
Pre- and postnatal medical care and risk of sudden infant death syndrome.
The current study investigated whether sufficient attendance at prenatal and postnatal checks affects the risk of sudden infant death syndrome. A case-control study in the Tyrol enrolled 99 infants with sudden infant death syndrome that occurred between 1984 and 1994, and 136 randomly selected control cases. The risk of sudden infant death syndrome was higher in infants whose mothers attended less than five antenatal health checks than in the group with at least five or more visits (OR 5.1; p < 0.01). Babies who received medical help beyond routine health controls had a lower risk than those who did not (OR 0.32; p < 0.001). These differences persisted when social and demographic variables (mother's age at delivery, educational level, marital status, parity and gestational age) were taken into account. Our study identified inadequate antenatal and postnatal care as a risk indicator for sudden infant death syndrome and as a potential target for further educational work. Clinical recommendations should await the results of further evaluations.
Austria↗
Persistent hyperplastic primary vitreous in a family with osteoporosis-pseudoglioma syndrome.
We had the opportunity to investigate the early abnormalities of the eyes in a family with osteoporosis-pseudoglioma syndrome. This syndrome combines severe premature osteoporosis with a bilateral eye disorder, leading to early onset blindness. Using colour doppler imaging in the 4-month-old girl from this affected family we demonstrated persistent hyperplastic primary vitreous in both eyes. Her brother's eyes had developed a partially calcified undefined mass. Our observation supports the hypothesis, that the disease gene may encode a matrix protein expressed in bone and eye.
Abnormalities, Multiple↗