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Biomedical subjects

B Steinmann

Publications and source records attributed to B Steinmann.

At least 181 records · Page 10Linked to original sources
PubMed1983

Multiple acyl-Co A dehydrogenation deficiency (MADD) in a boy with nonketotic hypoglycemia, hepatomegaly, muscle hypotonia and cardiomyopathy. Detection of N-isovalerylglutamic acid and its monoamide.

A boy, aged 7 months, of consanguineous parents presented with an acute onset of vomiting, fever, nonketotic hypoglycemia and acidosis and died from cardiac arrest after ventricular fibrillation. He had hepatomegaly and echocardiographically a non-obstructive cardiomyopathy. Autopsy was not allowed. After birth the child had suffered from a severe respiratory distress syndrome, transient metabolic acidosis and had a sweaty feet odour. Later on, development was retarded with a severe muscular hypotonia. Post mortem, numerous unusual organic acids were found in high concentrations in urine, e.g. dicarbonic acids, 2-hydroxyisobutyric, isovaleric, 3-hydroxyisovaleric acid, N-acyl glycines, isovalerylglutamic acid and sarcosine. This pattern indicated deficiencies of several acyl-Co A dehydrogenases in the metabolism of leucine, isoleucine, valine, lysine, short-chain fatty acids and sarcosine. This could be confirmed using cultured skin fibroblasts which were shown to degrade the corresponding labeled substrates insufficiently to 14CO2. It is assumed that the functional multiple acyl-Co A dehydrogenation deficiency is caused by a deficiency of a common link in the electron transfer system of these dehydrogenases which is inherited autosomal recessively in this family. Among the 12 patients reported, 7 died within the first 5 days of age.

Cardiomyopathies↗
PubMed1982

A new high performance liquid chromatography (HPLC) method for the quantitation of strychnine in urine and tissue extracts.

A high performance liquid chromatography (HPLC) method was developed for the quantitation of strychnine in urine of children with nonketotic hyperglycinaemia and other developmental disorders treated with the alkaloid. Mobile and stationary phases were polar, i.e. methanol-water-330 g/kg ammonia (volumes, 85 ml + 14.2 ml + 0.8 ml) and LiChrosorb Si-60, 7 microns. Brucine was the internal standard. Extraction was performed by the Extrelut technique. At strychnine nitrate concentrations in urine of 21, 126, and 70 micrograms/l, recovery was 92.1 +/- 8.7, 98.1 +/- 2.7, and 102.5 +/- 2.7%. A child with nonketotic hyperglycinaemia under continued strychnine treatment excreted 1 to 13.6% of the daily dose unmetabolized in urine. The method was also suitable for the estimation of unreacted strychnine in tissue extracts. The fast disappearance in vitro of strychnine from a guinea pig liver preparation was confirmed.

Amino Acid Metabolism, Inborn Errors↗
PubMed1981

The diagnosis of hereditary fructose intolerance.

Hereditary fructose intolerance (HFI) is a potentially life-threatening disorder and can be suspected from a detailed nutritional history. The usefulness of 2 diagnostic procedures, fructose tolerance test (FTT) and aldolase assay on biopsied liver, was studied. A standardized intravenous FTT with 200 mg/kg b.w. was done on 11 children with HFI, 17 age-matched contrast children, 6 adults with HFI and 6 adult controls. Blood glucose, phosphorus, urate, magnesium and fructose were followed for 2 hours. By the FTT, each HFI individual was reliably distinguished from controls and contrasts and even from those with acute liver disease other than HFI. Both children with non-HFI hepatopathy examined by both procedures had a normal FTT in spite of reduced liver fructaldolase activity. HFI children responded to the FTT by earlier and more pronounced hypoglycemia than adults, and one girl converted to an adult type response between the ages 12 and 181/2 years. Responses of two HFI sibling pairs and of one set of monozygotic twins were typical for age, but resemblance was no greater than within the unrelated HFI probands. The intravenous FTT is judged a reliable diagnostic tool, simple and harmless if done in hospital. Essential fructosuria is readily diagnosed by the FTT, but fructose-1,6-diphosphatase deficiency and HFI are not differentiated with certainty. Liver biopsies were obtained from 35 children with HFI, 14 contrast persons and 10 controls (of which 9 organ donors) and examined enzymatically. Deficiency of fructaldolase was observed in all HFI children but also in some contrast children suffering from acute liver disease other than HFI. In these, HFI could only be excluded when the reduced activity of reference enzymes such as fructose-1,6-diphosphatase and glucose-6-phosphatase and liver histology were included in the evaluation. In one deceased HFI infant, fructaldolase was deficient in both, liver and kidney cortex. Extent of antibody activation and of heat inactivation of residual fructaldolase varied between unrelated HFI patients but not within families. These results did not contribute to diagnosis but further documented genetic heterogeneity of HFI. For diagnosis of HFI we recommend 1. immediate elimination of fructose from the diet, 2. the intravenous FTT after several weeks of fructose withdrawal, and 3., should diagnosis still be uncertain, laparoscopic liver biopsy for assay of fructaldose and of reference enzymes and for histology.

Adult↗
PubMed1980

Evidence for a structural mutation of procollagen type I in a patient with the Ehlers-Danlos syndrome type VII.

We have found that the collagen from a patient with the Ehlers-Danlos syndrome type VII contained a polypeptide chain, pN alpha 2, not present in collagen prepared from normal tissue. Fibroblasts cultured from the patient's skin produced type I procollagen in which the NH2-terminal propeptide of pro alpha 2 was cleaved to about half of normal values by chick procollagen neutral protease which removes the NH2-terminal propeptides from procollagen (N-protease). The NH2-terminal propeptide on the pro alpha 2 chain of the patient's procollagen was also more resistant than procollagen from control fibroblasts to digestion by pepsin or alpha-chymotrypsin. assays for procollagen N-protease indicated that the patient's fibroblsts contained about the same level of enzymic activity as normal fibroblasts. These results suggest that the patient's fibroblasts synthesize both an abnormal pro alpha 2 chain and a normal pro alpha 2 chain. The abnormality probably consists of a structural mutation in or near the site at which procollagen N-protease cleaves the pro alpha 2 chain. The results presented here appear to provide the first example of a mutation in a structural gene for collagen. Since equal amounts of pN alpha 2 and alpha 2 are found in the protein in neutral salt extracts of the patient's tissue, as well as in newly synthesized collagen produced by cultured skin fibroblasts, and since both parents are phenotypically normal and express exclusively normal collagen chains, the patient is likely to be a sporadic heterozygote, arisen by new mutation, with one normal and one abnormal gene coding for pro alpha 2.

Cells, Cultured↗
PubMed1980

[Age dependent risk factors (author's transl)].

With increasing age the intrinsic disposition of diseases gains always more of importance facing the true causes of diseases. This disposition includes the totality of all changes of aging, which therefore have the significance of risk factors. There are mentionned several groups of age dependent risk factors, which can lead in different manner to real diseases. Since the importance of preventive geriatrics gets more and more important, it is indispensable to determine the aging processes so far as they have the significance of risk factors, and then to adjust the preventive measures. Age depending preventive geriatrics requires a continuous care and is specially the task of the practitioner or of the family doctor.

Aged↗
PubMed1979

[Catamnestic studies in hemiplegics].

61 patients with hemiplegia who had undergone hospital rehabilitation were examined 1 year later and 29 patients after an interval of 10--11 years. Special attention was paid to improvements and relapses with respect to walking ability, personal care, and social situation. The investigation showed that 62% of personal living on their own made progress in the activities of daily life; there were no relapses. 14% of those living in a family showed improvement while 29% relapsed. Of patients living in nursing homes only 5% showed improvement, while there were relapses in 42% of cases. The percentages of cases showing improvement (or relapses) with respect to walking ability are as follows: 20% (7.5%), 30% (22%) and 0% (21%). 32% of the patients had regular physiotherapy sessions. A change in the social situation had resulted for 50%; many of these were lonely and missed visitors. Persons looking after themselves showed the best prognosis following rehabilitation.

Activities of Daily Living↗
PubMed1979

Skin and bone lesions (dermato-osteolathyrism), possible side effects of D-penicillamine treatment, in a boy with cystinuria.

A 2 1/4 year-old boy was treated for cystinuria and urolithiasis with high fluid intake, sodium bicarbonate, and D-penicillamine, over a period of 5 3/4 years, unauthorized interruptions and prescribed pauses included. Therapy was partially sucessful but regrowth of calculi coincided with interruptions of D-penicillamine administration and also with the institution of a low-dose D-penicillamine regime. Flat feet, scoliosis, pectus carinatum, hypermobility of joints, molluscoid pseudotumors and atrophic scars were alarming side effects of D-penicillamine. However, the possibility was not excluded that a forme fruste of an Ehlers-Danlos syndrome preexisted in this boy and was effected by D-penicillamine. Only the molluscoid pseudotumors regressed when D-penicillamine was reduced or omitted temporarily. Osteolathyrism caused by D-penicillamine has hitherto not been reported in man.

Atrophy↗
PubMed1979

Abnormal collagen fibril structure in the gravis form (type I) of Ehlers-Danlos syndrome.

The Ehlers-Danlos syndrome (EDS) is a clinically, genetically, and biochemically heterogeneous group of disorders characterized by generalized connective tissue abnormalities. We studied collagen fibrils by electron microscopy in the dermis of nine individuals with clinical findings consistent with type I Ehlers-Danlos syndrome. In all patients the collagen fibrils had an increased mean diameter (13 to 40%) and showed a higher degree of variability in width and shape than collagen fibrils from controls. Approximately 5% of the fibrils were much wider (up to 500 nm. versus 90 nm.), had a highly irregular outline when viewed in cross-section, and were spiraled and fragmented in longitudinal view. The periodicity of banding was normal. The mode of inheritance was dominant in five patients, probably recessive in two, and could not be determined in the remaining two. Despite genetic heterogeneity among these patients with type I Ehlers-Danlos syndrome, the ultrastructural findings are indistinguishable and do not allow discrimination in sporadic cases between the recessive and the more common dominant form. We conclude that abnormalities of fibrillogenesis are heterogeneous in origin; some might be due to primary defects in collagen whereas others may result from alterations of noncollagenous extracellular matrix components that influence collagen fibril formation.

Adolescent↗
PubMed1979

Congenital defect in intracellular cobalamin metabolism resulting in homocystinuria and methylmalonic aciduria. II. Biochemical investigations.

Biochemical investigations are reported in an infant with methylmalonic aciduria and homocystinuria who died at 4 months of age. Postmortem analysis of liver obtained 2 weeks after the child was treated with vitamin B12 revealed deficient activity of both cobalamin dependent enzymes: N5-methyltetrahydrofolate: homocysteine methyltransferase (requiring Me-Cbl), and methylmalonyl CoA mutase (requiring Ado-Cbl). MMA-CoA mutase activity could be restored to normal in vitro by added Ado-Cbl, but MeTHF-HCy transferase activity was not significantly enhanced by addition of Me-Cbl. Though the serum total cobalamin was normal, total cobalamin in liver and kidney was abnormally low. In the kidney Me-Cbl and Ado-Cbl were disproportionally decreased whereas in the liver only Ado-Cbl was significantly reduced. This suggests that at least some of the CN-Cbl administered was converted to the coenzymes in liver which would explain the reduction of MMA- and HCy-excretion during therapy. The results show 1. that this infant suffered from a congenital defect in one of the steps of intracellular cobalamin metabolism or transport common to the synthesis of both coenzymes, 2. that life-long treatment with vitamin B12 (OH-Cbl) may be of value in similar cases, particularly if given early in the course of the disease.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1979

Congenital defect in intracellular cobalamin metabolism resulting in homocysteinuria and methylmalonic aciduria. I. Case report and histopathology.

The case is described of an infant who suffered from progressive, severe dystrophy, hemolytic and megaloblastic anemia, hematuria, proteinuria and slight uremia. He died at 4 months of age following two acute episodes of heart failure. Abnormally increased excretion of methylmalonate and homocystine was detected by our screening program for metabolic disorders. Amino acid analyses showed that the plasma and urine levels of methionine were very low whereas those of cystathionine were raised. Vitamin B12 deficiency, malabsorption or abnormal cobalamin transport were excluded by a normal serum total cobalamin and normal transcobalamins. These findings suggested a congenital error of cobalamin metabolism. Treatment with vitamin B12 resulted in a biochemical though not a clinical response. Postmortem examination revealed severe vascular lesions with changes in the kidney characteristic of thrombotic microangiopathy supporting a diagnosis of hemolytic-uremic syndrome. It is assumed that the elevated plasma homocysteine induced the vascular lesions by causing detachment of endothelium.

Blood Vessels↗
PubMed1979

Strychnine treatment attempted in newborn twins with severe nonketotic hyperglycinemia.

Strychnine, a potent antagonist of glycine was given to twins suffering from nonketotic hyperglycinemia at age 73 hours. Within hours of the onset of treatment favorable effects were observed such as improvements of muscle tone, movements, defense reactions, and probably breathing. Pyridoxine, N5-formyl-tetrahydrofolate and lipoic acid were given concomitantly with strychnine but failed to alter glycine levels in plasma and cerebrospinal fluid. The therapeutic trial was terminated after 2 1/2 days because success, though considerable, was judged inadequate.

Diseases in Twins↗