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Biomedical subjects

U Langenbeck

Publications and source records attributed to U Langenbeck.

At least 19 recordsLinked to original sources
PubMed2006

Variant maple syrup urine disease (MSUD)--the entire spectrum.

BACKGROUND: In the rare inborn autosomal recessive disorder maple syrup urine disease (MSUD) the accumulation of the branched-chain amino acids (BCAAs) and their metabolic products results in acute and chronic brain dysfunction. About 20% of the patients suffer from non-classic variant forms of MSUD of different clinical severity. AIM: Up to now variant cases have mostly been published as individual case reports; the aim of this study was to give a comparative description of 16 individuals (aged 6-30 years) with different forms of variant MSUD. METHODS: Laboratory data, information on clinical course and treatment as well as aspects of developmental, intellectual and social outcome were obtained retrospectively. Data from in vitro and in vivo methods measuring the degree of enzyme deficiency were included. RESULTS: In addition to a mild phenotype, which fits well into the so-called intermittent variant, and a more severe phenotype with a wider range from a mild variant to an almost classic form, which fits well into the so-called intermediate variant, we assume the existence of an asymptomatic, non-disease variant of MSUD. These clinical phenotypes are not unambiguously differentiable on the basis of biochemical parameters. CONCLUSION: A continuum of clinical severity from asymptomatic to very severe (border to classic) exists in variant MSUD. Apart from newborns with classic MSUD, also those with variant forms benefit from early diagnosis and start of adequate treatment.

Adolescent↗
PubMed2005

Predicting the phenylalanine blood concentration from urine analyses. An approach to noninvasive monitoring of patients with phenylketonuria.

The need for regular blood-drawing in the management of chronic metabolic disorders may negatively influence the compliance of patients and their parents; noninvasive analytical procedures could well alleviate this burden. Using data obtained in six adult probands with phenylketonuria, we evaluate the feasibility of noninvasive prediction of phenylalanine blood concentrations from analysis of phenylalanine and creatinine in urine. Cross-validated regression equations correct for the significant inter-individual variation of phenylalanine fractional excretion rates. With sensitive and specific enzymatic assays for phenylalanine and creatinine, the accuracy of this noninvasive procedure may also become clinically satisfactory for the purpose of self-monitoring.

Adult↗
PubMed2003

A glimpse into genomeland.

This selective review of current genetic paradigms and procedures, presented in the context of surprising discoveries from the entire field of clinical and experimental genetics, may serve as a primer for the in-depth reviews of this volume. The rapid progress in clinical and molecular genetics requires continuing education and self-study of practising physicians to keep abreast of the developments that form the expanding field of genetic and molecular medicine.

Animals↗
PubMed2001

Modelling the phenylalanine blood level response during treatment of phenylketonuria.

A vast body of phenylketonuria (PKU) patient monitoring data is deposited in clinical files and, after having served the actual needs, has remained there largely unused. We propose a kinetic model that will allow continued analysis of such data for further elucidation of the patient's metabolic phenotype and phenylalanine (Phe) disposal characteristics. Our PKU model of a single compartment with the input of alimentary Phe and two outputs--(1) first-order Phe conversion to tyrosine and acidic metabolites, and (2) zero-order Phe usage for net protein synthesis--has been developed with the graphics-oriented ModelMaker (then Cherwell Scientific Ltd, Oxford, UK) software package. The corresponding differential and integrated rate equations are presented to enable transfer of the model to equation-oriented simulation packages. The model offers a possible explanation for discrepancies in some genotype-phenotype data.

Child↗
PubMed2000

[Family study of patients with aspirin intolerance and rhinosinusitis].

The high prevalence of aspirin intolerance in asthmatics and patients with nasal polyps as well as reports of familial clustering suggest a genetic disposition of this disease. Our study aimed at obtaining further evidence of hereditary factors in this disease. We included 33 unselected patients from 28 families with aspirin intolerance and rhinosinusitis in this study. Controls were recruited from individuals treated in our ENT clinic for diseases other than aspirin intolerance (n = 52). A questionnaire focused on family histories as well as reports on diseases of the upper respiratory tract or allergies. ASS intolerance was verified either by bronchial or nasal provocation tests. We found cases of aspirin intolerance among parents, siblings, and children of ASS intolerant probands. The children of probands had nasal polyps and rhinosinusitis more often than the children of controls. We propose that ASS intolerance with nasal polyps and asthma represents a complex phenotype, with genetic and environmental factors contributing to its manifestation.

Adolescent↗
PubMed2000

Parent-offspring resemblance of palmar and plantar dermatoglyphic patterns in Down syndrome.

With the aim of investigating the influence of trisomy 21 on the expression of heritable morphological features, we recorded the palmar and plantar dermatoglyphic patterns in 48 children with Down syndrome (DS), in both their parents, and, as a control, in 57 of their siblings. Using the Kendall tau rank correlation test, a considerable parental influence on the frequency of true patterns in the interdigital areas (IDA) III and IV of the palms (P = 0.3%) and soles (P = 1.0% and 3.8%, respectively) is demonstrated for the control siblings. In the children with DS, this influence is discernible as well, although with no statistical significance. A greater number of families may be required to settle the question.

Down Syndrome↗
PubMed1996

Towards self-monitoring and self-treatment in phenylketonuria--a way to better diet compliance.

It has been a long established principle in the treatment of diabetes that the patient or his/her family is responsible for day-to-day monitoring of metabolic control. It is believed that this concept should also now be applied in phenylketonuria. At present, self-monitoring of blood phenylalanine still requires assaying the phenylalanine concentration in capillary blood obtained by finger-stick sampling at home, via mailing to a nearby laboratory. Frequently and rapidly obtained data can guide the patient to adjust dietary phenylalanine intake, provided he and his family have been informed in detail about the disease and trained in practical diet competence. Teaching programmes for patients are to be promoted. A home-monitoring device for blood phenylalanine is at the development stage.

Humans↗
PubMed1995

Crigler-Najjar syndrome type II. New observation of possible autosomal recessive inheritance.

The inheritance of Crigler-Najjar syndrome type II (CNS II) is still unclear. Both autosomal dominant transmission with variable penetrance and autosomal recessive transmission have been reported. We describe the diagnosis of CNS II in an adult patient with unconjugated serum bilirubin levels up to 19.6 mg/dl and no detectable activity of bilirubin UDP-glucuronosyltransferase in the liver biopsy. Serum bilirubin levels decreased markedly on phenobarbital treatment. The parents of our patient are first cousins. The mother and three of the patient's five sibs were jaundiced within a few days of birth. Our patient and her jaundiced siblings have 11 children, all healthy and anicteric. We conclude from these data that the inheritance of this very rare disease follows an autosomal recessive pattern, with pseudodominance in this family.

Adult↗
PubMed1995

[Genetic diagnosis and therapy of hereditary breast carcinoma].

Congenital genetic disturbances in the genes BRCA1 and BRCA2 could lead to the forming of mamacarcinoma and ovarian carcinomas. The probability of illness is by an existing gene defect very high, and mostly young women are already affected. A direct anamnestic identification of high risk person with a following proof of gene mutations could help the patient. The way of the clinical-consultation which is recommending the BRCA1-BRCA2-test in reasons for an early recognition diagnosis is at the moment subject in clinical and scientific research.

BRCA2 Protein↗
PubMed1992

Determination of (S)- and (R)-2-oxo-3-methylvaleric acid in plasma of patients with maple syrup urine disease.

An enzymatic method for the separate measurement of both chiral 2-oxo-3-methylvaleric acid (OMV) compounds, (S)- and (R)-OMV, by NADH-dependent enantioselective amination using leucine dehydrogenase in the presence of a NADH regenerating system is described. This method allows the quantitative determination of all branched-chain 2-oxo acids, simultaneously. In plasma samples from classical maple syrup urine disease patients under therapy the average (R)-OMV/(S)-OMV ratio was 0.35 and great differences in the transamination equilibria of the diastereomeric branched-chain amino acids L-isoleucine and L-alloisoleucine were demonstrated.

Amino Acid Oxidoreductases↗
PubMed1992

A synopsis of the unconjugated acidic transamination metabolites of phenylalanine in phenylketonuria.

We present blood and urine levels of unconjugated o-hydroxyphenylacetic, phenyllactic and phenylpyruvic acids in 61 children (2 years of age and above) and juveniles with phenylketonuria on or partially off diet. The samples were obtained during 185 scheduled outpatient visits and have been analysed with gas chromatographic methods. The compiled data define reference ranges of phenylalanine transamination capacity and of renal transport of metabolites which may be of value in further studies on the pathogenesis of phenylketonuria.

Adolescent↗
PubMed1991

Sphingolipid activator protein 1 deficiency in metachromatic leucodystrophy with normal arylsulphatase A activity. A clinical, morphological, biochemical, and immunological study.

A 7-year-old boy had clinical features of metachromatic leucodystrophy (MLD), however, an increased urinary sulphatide excretion was found in the presence of normal arylsulphatase A (and alpha-galactosidase A) activity. A rectal biopsy showed metachromatically staining storage macrophages as well as nonmetachromatic, but PAS-positive, submucosal neurons filled with membranous cytoplasmic bodies. These two types of storage material led to testing for a sphingolipid activator protein (SAP) deficiency. Loading tests with sulphatide and globotriaosylceramide showed deficient turnover of both sphingolipids in cultured fibroblasts. Using the Ouchterlony method, there was no reactivity between a described anti-SAP 1 antiserum and the patient's fibroblast extracts. This new case of SAP-1 deficient MLD was compared with the four cases of this variant known from the literature. Our results indicate that rectal biopsy morphology and lipid loading biochemistry should prove useful for the screening of SAP defects.

Biopsy↗
PubMed1991

Oral L-alloisoleucine loading studies in healthy subjects and in patients with maple syrup urine disease.

Total body and renal elimination of L-alloisoleucine was assessed after oral loads (0.57 mmol/kg body wt) in four healthy subjects and in five patients with maple syrup urine disease (MSUD) of different degrees of severity. As judged from the fictive initial concentration, L-alloisoleucine is distributed evenly in the total body water space. In the controls, estimated half-time of total elimination was 9.2 +/- 2.2 h (n = 4). In the MSUD patients, it ranged from 26 h (mild variant) to about 8 d (classical type). Because of its low renal clearance rate, L-alloisoleucine was cleared through ketomethylvalerate to greater than 99% in normals and to at least 73% in the MSUD patients. Assuming small variation in the losses of ketomethylvalerate through L-isoleucine formation and through renal excretion, this test allows ranking of MSUD patients with regard to their residual in vivo branched-chain oxo-acid dehydrogenase activity.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗