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Biomedical subjects

O A Bodamer

Publications and source records attributed to O A Bodamer.

At least 19 recordsLinked to original sources
PubMed2006

Glucose and leucine kinetics in idiopathic ketotic hypoglycaemia.

AIMS: To investigate glucose and leucine kinetics in association with metabolic and endocrine investigations in children with ketotic hypoglycaemia (KH) in order to elucidate the underlying pathophysiology. METHODS: Prospective interventional study using stable isotope tracer in nine children (mean age 4.23 years, range 0.9-9.8 years; seven males) with KH and 11 controls (mean age 4.57 years, range 0.16-12.3 years; four males). RESULTS: Plasma insulin levels were significantly lower in KH compared to subjects in the non-KH group. Plasma ketone body levels were significantly higher in KH than in non-KH. Basal metabolic rate was significantly higher in subjects with KH (45.48+/-7.41 v 31.81+/-6.72 kcal/kg/day) but the respiratory quotients were similar in both groups (KH v non-KH, 0.84+/-0.05 v 0.8+/-0.04. Leucine oxidation rates were significantly lower in children with KH (12.25+/-6.25 v 31.96+/-8.59 micromol/kg/h). Hepatic glucose production rates were also significantly lower in KH (3.84+/-0.46 v 6.6+/-0.59 mg/kg/min). CONCLUSIONS: KH is caused by a failure to sustain hepatic glucose production rather than by increased glucose oxidation rates. Energy demand is significantly increased, whereas leucine oxidation is reduced.

Alanine↗
PubMed2005

Use of denaturing HPLC to provide efficient detection of mutations causing guanidinoacetate methyltransferase 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 symptoms. To date, 14 mutations of the GAMT gene in 27 patients have been reported. Mutation analysis was done using direct sequencing of PCR products and denaturing gradient gel electrophoresis in combination with direct sequencing. In contrast, we evaluated the efficiency of a newly developed DHPLC method to detect mutations in the GAMT gene by analysing DNA from 14 GAMT patients with known mutations. PCR amplification of both patient and control DNA was followed by formation of homoduplices and heteroduplices, and their detection by DHPLC. DHPLC identified all mutations tested and is the preferred choice of analytical method.

Base Sequence↗
PubMed2005

Late-onset neurologic disease in glutaryl-CoA dehydrogenase deficiency.

Neurologic disease in glutaryl-CoA dehydrogenase (GCDH) deficiency usually presents with acute encephalopathic crises before 2 years of age. The authors report two previously asymptomatic patients with macrocephaly presenting with progressive neurologic deterioration and a severe leukoencephalopathy during adolescence or adulthood.

Age of Onset↗
PubMed2005

Lack of correlation between fatty acid oxidation disorders and haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome?

AIM: Fatty acid beta-oxidation defects comprise a heterogeneous group of disorders that may precipitate acute life threatening metabolic crises particularly during catabolic episodes. Several studies have demonstrated a possible association between fatty acid beta-oxidation defects, including long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and severe pregnancy complications. However, the precise percentage of women with haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome associated with foetal fatty acid beta-oxidation defects is not known. METHODS: We carried out a multicentre retrospective study on 88 infants, born to women with HELLP syndrome. Acylcarnitine profiles from blood dried on filter paper cards were analysed by tandem mass spectrometry for the diagnosis of fatty acid beta-oxidation defects. In addition, we screened for the common long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mutation using a standard restriction fragment length polymorphism polymerase chain reaction method. RESULTS: None of the infants studied carried the common long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mutation. There was no evidence of fatty acid beta-oxidation defects, including long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, as expected by unremarkable acylcarnitine profiles, while three infants with fatty acid beta-oxidation defects were diagnosed in the control group. CONCLUSIONS: Neither foetal long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, including heterozygosity for the common long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency mutation, nor fatty acid beta-oxidation defects in general are a major risk factor for HELLP syndrome in Austria.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2004

Nuclear magnetic resonance spectroscopy in glutaryl-CoA dehydrogenase deficiency.

Nuclear magnetic resonance (NMR) spectroscopy is a safe, noninvasive method that is the preferred technique for in vivo analysis of specific chemical compounds in localized brain regions. Besides quantification of compounds, NMR spectroscopy allows the detailed analysis of neurotransmitter, glucose and lactate metabolism following peripheral infusions of stable isotopically labelled precursors. The latter has been successfully applied to patients with different neurological disease states not including glutaryl-CoA dehydrogenase (GCDH) deficiency. In contrast, single patients with GCDH deficiency who were neurologically unremarkable have been studied with conflicting results. One patient was shown to have an increase in intracerebral creatine and phosphocreatine concentrations, while the second studied had unremarkable levels. In a 15-year-old patient, we were able to demonstrate elevated levels of intracerebral lactate and elevated choline/N -acetylaspartate ratios, indicating potentially increased myelin turnover and reduced neuronal integrity in periventricular white matter. Interestingly, spectra in basal ganglia were within normal limits. Systematic studies to address well-defined questions in GCDH deficiency are urgently needed. In particular, analysis of in vivo neurotransmitter metabolism following administration of isotopically labelled precursors in patients with GCDH deficiency, both when metabolically stable and when unstable, may help to advance our understanding of the pathophysiology of GCDH deficiency.

Adolescent↗
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↗
PubMed2003

Reversibility of cirrhotic regenerative liver nodules upon NTBC treatment in a child with tyrosinaemia type I.

UNLABELLED: In a male patient with hereditary tyrosinaemia type I (HTI), NTBC [2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexandion] treatment and a diet low in phenylalanine and tyrosine were started at the age of 4 wk. At the recommended average dosage (1 mg kg(-1)), liver failure improved transiently. After 4 mo of treatment, with increased body weight, the dose had decreased to 0.7 mg kg(-1), and diffuse cirrhotic changes in liver parenchyma and multiple nodules were visualized by ultrasonography. Multiple nodules in the liver parenchyma were differentiated from hepatocellular carcinoma by magnetic resonance imaging (MRI) using mangafodipir trisodium as a paramagnetic liver-specific contrast agent. Augmentation of NTBC dosage resulted in a decrease in serum alpha-fetoprotein levels and in significant regression of liver nodules on MRI. CONCLUSION: In HTI patients with a poor response to NTBC treatment and/or development of cirrhotic changes of liver parenchyma, augmentation of the recommended NTBC dosage may result in significant improvement of symptoms.

Cyclohexanones↗
PubMed2001

Atypical presentation of amniotic band sequence.

Amniotic Band Sequence (ABS) is a disruption sequence that results in a variable group of abnormalities secondary to the disruption process and subsequent deformations. The incidence of ABS ranges from 1:1,200 to 1:15,000 live-born, and is even higher in still-born [Froster and Baird, 1993: Am J Med Genet 46:497-500]. The pathophysiology of ABS remains controversial, but a close look to critical periods of embryogenesis and/or organogenesis has helped in understanding pathogenetic mechanisms leading to the ABS disruption. The abnormalities are typically limited to external structures; however, associated internal malformations as seen in the case reported here may occur [Hunter and Carpenter, 1986: Am J Med Genet 24:691-700]. The prognosis depends on the severity of the abnormalities and the involvement of internal organs [Froster and Baird; 1993: Am J Med Genet 46:497-500; Levy, 1998: Ped Rev 19:249].

Amniotic Band Syndrome↗
PubMed2001

Analysis of guanidinoacetate and creatine by isotope dilution electrospray tandem mass spectrometry.

Guanidinoacetate methyltransferase (GAMT) deficiency is a disorder of creatine metabolism characterized by low plasma creatine concentrations in combination with elevated guanidinoacetate (GAA) concentrations. Although rare, GAMT deficiency has been identified in children with seizures, extrapyramidal movements, developmental delay, myopathies and behavioral abnormalities. Treatment with creatine monohydrate has been proven to be effective. We describe an isotope dilution electrospray tandem mass spectrometry (ES-MS/MS) assay for the simultaneous determination of plasma GAA and creatine using multiple reaction monitoring (MRM), d(3)-creatine as the internal standard and derivatization of GAA and creatine as butyl-esters. We analysed plasma of 16 healthy adults and 20 healthy children as well as three affected children. Plasma GAA concentrations were 5.02+/-1.84 micromol/l (mean+/-S.D.) in adults, 3.91+/-0.76 micromol/l in children age 5-10 years and 11.57, 15.16, 14.36 micromol/l in children with GAMT deficiency. Plasma creatine concentrations were 34.7+/-15.25 micromol/l in adults, 58.96+/-22.30 micromol/l in children and 5.37, 8.15, 403.5 micromol/l in two untreated children and one treated child with GAMT deficiency, respectively. GAA can also be reliably measured from filter cards, which is sufficient to make the correct diagnosis while creatine is consistently falsely elevated probably secondary to liberation of red cell creatine. In nine healthy newborn infants, GAA concentrations from filter cards were 4.83+/-1.43 and 5.04+/-1.84 micromol/l in 16 healthy adults. We conclude that isotope dilution ES-MS/MS is ideal for rapid high-throughput diagnosis of GAMT deficiency both from plasma and filter paper cards. Using this technique neonatal screening is feasible for this treatable inborn error of creatine metabolism.

Adult↗
PubMed2001

Mitochondrial DNA depletion associated with partial complex II and IV deficiencies and 3-methylglutaconic aciduria.

We report a patient with mitochondrial DNA depletion, partial complex II and IV deficiencies, and 3-methylglutaconic aciduria. Complex II deficiency has not been previously observed in mitochondrial DNA depletion syndromes. The observation of 3-methylglutaconic and 3-methylglutaric acidurias may be a useful indicator of a defect in respiratory chain function caused by mitochondrial DNA depletion.

Biopsy↗
PubMed2000

The effects of l-alanine supplementation in late-onset glycogen storage disease type II.

Myopathy in glycogen storage disease type II (GSD-II) is slowly progressive. Five subjects with the late-onset form of GSD-II (age range, 15 to 47 years) and seven healthy control subjects (age range, 28 to 55 years) were studied. Following alanine supplementation, resting energy expenditure decreased in patients with GSD-II (p < 0.05) compared to values seen in control subjects. Leucine flux decreased (p < 0.004), as did leucine oxidation, to levels lower than those observed in control subjects (p < 0.001). l-Alanine reduces protein turnover and catabolism in GSD-II.

Adolescent↗
PubMed2000

Deletion (9) (p13.1 p21.1).

We report on a 22-month-old girl with minor facial anomalies, global developmental delay, growth retardation, seizures, and leukoencephalopathy. Initial clinical assessment suggested the diagnosis of Williams syndrome. Results of fluorescence in situ hybridization testing for elastin were normal. However, chromosome analysis showed a 46,XX,del(9)(p13.1p21.1) karyotype in peripheral lymphocytes. Parental chromosomes were normal, indicating a de novo deletion. This patient's manifestations are compared with those of two other cases with overlapping deletions of the proximal short arm of chromosome 9.

Chromosome Banding↗
PubMed2000

Psychiatric symptoms of inherited metabolic disease.

Inborn errors of metabolism often present with a variety of psychiatric symptoms. With improved diagnosis and treatment options, many patients have increased lifespans; consequently, issues of long-term quality of life are coming to the forefront. Mental health concerns are among these issues. To demonstrate the connection between the course of metabolic disease and its psychiatric manifestations, four different inborn errors of metabolism are reviewed: phenylketonuria, Wilson disease, acute intermittent porphyria, and metachromatic leukodystrophy.

Hepatolenticular Degeneration↗