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Biomedical subjects

F Hanefeld

Publications and source records attributed to F Hanefeld.

At least 109 records · Page 6Linked to original sources
PubMed1994

Deletion screening of mitochondrial DNA via multiprimer DNA amplification.

We report an application of multiprimed polymerase chain reaction (PCR) which allows a rapid, nonradioactive detection of deletions in mitochondrial DNA using EDTA-blood and muscle samples. The use of two primer sets consisting of three forward and five reverse primers, respectively, allows a competitive PCR resulting in significant amplification products only in the presence of deletion-harbouring DNA species. Under the conditions described, deletions causing Kearns-Sayre syndrome (KSS) and progressive external ophthalmoplegia (PEO) have been successfully detected. The location of the primers on mitochondrial DNA used in this study should allow identification and localization of most of the large-scale deletions (i.e. more than 1 kb) of mitochondrial DNA reported so far.

Base Sequence↗
PubMed1994

Giant axonal neuropathy: a generalized disorder of intermediate filaments with longitudinal grooves in the hair.

Giant axonal neuropathy (GAN) is a generalized neurological disorder with accumulation of intermediate filaments in different cell populations. The hallmark are enormous axonal swellings containing densely packed neurofilaments. Clinical symptoms reported so far are mainly limited to the nervous system. We report on a four-year-old girl with clinical and sural nerve biopsy findings typical of GAN. In addition, scanning electron microscopy (SEM) showed longitudinal grooves in the hairs of our patient. This peculiarity so far has only been described in two other patients with GAN. Scanning electron microscopy of hairs therefore may serve as a method of screening in patients suspected of suffering from GAN.

Axons↗
PubMed1994

Interstitial deletion of 22q11 in DiGeorge syndrome detected by high resolution and molecular analysis.

Two patients with DiGeorge syndrome (DGS), one with and one without characteristic dysmorphic facial features, were studied by high resolution banding, fluorescence in situ hybridization (FISH) and quantitative Southern blotting. In both patients, even in the one with no typical facial stigmata, a microdeletion within 22q11.2 was detected. FISH analysis, in particular, is most useful in screening for 22q11.2 segmental monosomy in patients with DGS and DGS-related features.

Blotting, Southern↗
PubMed1994

Creatine deficiency in the brain: a new, treatable inborn error of metabolism.

In a patient with extrapyramidal movement disorder and extremely low creatinine concentrations in serum and urine, in vivo proton magnetic resonance spectroscopy disclosed a generalized depletion of creatinine in the brain. Oral substitution of arginine, a substrate for creatine synthesis, resulted in an increase of brain guanidinoacetate as the immediate precursor of creatine but did not elevate cerebral creatine levels. In contrast, oral substitution of creatine-monohydrate led to a significant increase of brain creatine, a decrease of brain guanidinoacetate, and a normalization of creatinine in serum and urine. Phosphorus magnetic resonance spectroscopy of the brain revealed no detectable creatine-phosphate before oral substitution of creatine and a significant increase afterward. Partial restoration of cerebral creatine concentrations was accompanied by improvement of the patient's neurologic symptoms. This is the first report of a patient with complete creatine deficiency in the brain. Magnetic resonance spectroscopy during arginine and creatine treatment point to an inborn error of creatine biosynthesis at the level of guanidinoacetete-methyltransferase.

Arginine↗
PubMed1994

Linkage of a locus for carbohydrate-deficient glycoprotein syndrome type I (CDG1) to chromosome 16p, and linkage disequilibrium to microsatellite marker D16S406.

Carbohydrate-deficient glycoprotein syndrome type I is a multisystem disease with early severe nervous system involvement. The disease, which is inherited as an autosomal recessive trait, is biochemically characterized by complex defects in the terminal carbohydrate residues of a number of serum glycoproteins. This can be most readily detected in transferrin. A whole genome scan was initiated in order to localize the gene (CDG1) with linkage techniques. We analyzed individuals from 25 CDG1 pedigrees with several highly polymorphic microsatellite markers and after exclusion of about 30% of the genome linkage was detected with markers located in chromosome region 16p. The lod score (Zmax) was above 8 (theta max = 0.00) for several markers in this region. In order to further localize the CDG1 gene, recombination and linkage disequilibrium analyses were performed. Recombination events in some pedigrees indicated that the CDG1 gene is located in a 13 cM interval between microsatellite markers D16S406 and D16S500. Furthermore, allelic association was shown for marker D16S406 indicating that the CDG1 gene is located close to this. No heterogeneity could be detected in the European family material tested by us. The positions of cytogenetically localized flanking markers suggest that the location of the CDG1 gene is in chromosome region 16p13.3-p13.12.

Alleles↗
PubMed1994

In vivo proton magnetic resonance spectroscopy of the brain in a patient with L-2-hydroxyglutaric acidemia.

Morphologic appearance and metabolic disturbances of the brain of a patient with L-2-hydroxyglutaric acidemia were investigated with use of magnetic resonance imaging and localized proton magnetic resonance spectroscopy in vivo. Whereas magnetic resonance imaging revealed increased internal and external cerebrospinal fluid spaces as well as patchy white matter lesions, metabolic deviations included a 50% decrease of N-acetylaspartate (neuronal marker), a 75% increase of myo-inositol (glial marker), and a 40% decrease of choline-containing compounds in white matter relative to age-matched controls. A clinical deterioration of the patient was clearly reflected in a follow-up examination 22 mo later, resulting in a further reduction of N-acetylaspartate and a more pronounced enhancement of myo-inositol. No elevation of lactate was observed. The magnetic resonance spectroscopy findings are in line with a generalized neurodegenerative process in L-2-hydroxyglutaric acidemia but also suggest a defect in phosphatidyl inositol metabolism of glial cells.

Adolescent↗
PubMed1993

Quantitative organic acid analysis in cerebrospinal fluid and plasma: reference values in a pediatric population.

Quantitative reference values for the concentrations of organic acids in cerebrospinal fluid (CSF) and plasma, as well as ratios of individual organic acids between CSF and plasma, were determined in twenty-three pairs of samples from pediatric patients. Twenty-six organic acids were present and quantifiable in all or the majority of plasma and CSF specimens (limit of detection 1 mumol/l). There were substantial differences between subgroups of organic acids, best reflected by the ratios of individual acids between CSF and plasma. Metabolites related to fatty acid oxidation were present in CSF in substantially lower amounts than in plasma. Organic acids related to carbohydrate and energy metabolism and to amino acid degradation were present in CSF in equal or slightly lower amounts than in plasma. Finally, some organic acids were found in substantially higher amounts in CSF than in plasma, e.g. glycolate, glycerate, 2,4-dihydroxybutyrate, citrate and isocitrate. Quantitation of organic acids in CSF and plasma should aid diagnosis and monitoring of treatment of patients with organic acid disorders.

Acids↗
PubMed1993

L-2-hydroxyglutaric acidaemia: clinical and biochemical findings in 12 patients and preliminary report on L-2-hydroxyacid dehydrogenase.

L-2-Hydroxyglutaric acidaemia represents a newly defined inborn error of metabolism, with increased levels of L-2-hydroxyglutaric acid in urine, plasma and cerebrospinal fluid. The concentration in cerebrospinal fluid is higher than in plasma. The other consistent biochemical finding is an increase of lysine in blood and cerebrospinal fluid, but lysine loading does not increase L-2-hydroxyglutaric acid concentration in plasma. This autosomal recessively inherited disease is expressed as progressive ataxia, mental deficiency with subcortical leukoencephalopathy and cerebellar atrophy on magnetic resonance imaging. Since these features were described in 8 patients by Barth and co-workers in 1992, 4 more patients with similar findings have been diagnosed and added to the present series. L-2-Hydroxyglutaric acid is found in only trace amounts on routine gas chromatographic screening in normal persons, and its origin, its fate and even its relevance to normal metabolism are unknown. Therefore its catabolism was studied in normal liver. Incubation of rat liver with L-2-hydroxyglutaric acid did not produce H2O2, which excluded (peroxisomal) L-2-hydroxyacid oxidase as the main route of catabolism. However, L-2-hydroxyglutaric acid is rapidly dehydrogenated if NAD+ is added as a co-factor to the standard reaction medium. This could also be demonstrated in human liver. The preliminary evidence for this enzyme activity in rats and humans, L-2-hydroxyglutaric acid dehydrogenase, is given. Further investigations are required to clarify the possible relevance to the metabolic defect in L-2-hydroxyglutaric acidaemia.

Adolescent↗
PubMed1993

Alterations of brain metabolites in metachromatic leukodystrophy as detected by localized proton magnetic resonance spectroscopy in vivo.

The brain morphology and chemistry of seven children with late infantile (4/7) and juvenile (3/7) forms of metachromatic leukodystrophy (MLD) were investigated by magnetic resonance imaging (MRI) and localized proton magnetic resonance spectroscopy (MRS). Patients who were examined at least 6 months after the onset of symptoms (6/7) had severe leukodystrophic changes on MRI. Proton MRS revealed a marked reduction of the neuronal marker N-acetylaspartate in white and grey matter and elevated lactate in demyelinated areas. In contrast to other leukodystrophies MLD patients showed a generalized increase of brain myo-inositol (2- to 3-fold in white matter), indicating a specific role in the pathophysiology of demyelination in MLD.

Adolescent↗
PubMed1993

Diffuse white matter disease in three children: an encephalopathy with unique features on magnetic resonance imaging and proton magnetic resonance spectroscopy.

Amongst 21 children with unclassified white matter diseases three patients could be characterised by an identical clinical picture, magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) findings as a probably distinct entity. Following a normal early development they later showed rapidly progressive motor symptoms (ataxia, spasticity) leading to severe handicap within one or two years after onset. Later on bulbar symptoms, optic atrophy and epileptic seizures occurred. The MRI showed a diffuse homogeneous hypodensity of the white matter almost identical to the signal of the ventricles. MRS revealed a near total absence of N-acetylaspartate, choline and creatine and an increase of lactate and glucose. One girl and one boy were siblings, indicating an autosomal recessive trait.

Aspartic Acid↗
PubMed1993

Epidemiology and clinical manifestations of Lyme borreliosis in childhood. A prospective multicentre study with special regard to neuroborreliosis.

Lyme borreliosis is a tick-borne infection caused by the spirochete Borrelia burgdorferi, whose discovery in 1982 solved an aetiological mystery involving a variety of dermatological and neurological disorders and explained their association with Lyme disease. Lyme borreliosis occurs frequently and is readily treatable with antibiotics. Along with its discovery, however, came the realization that it is difficult to diagnose accurately, especially antibody diagnosis. False-positive antibody results in particular led to gradual widening of the clinical spectrum, and differential diagnosis became increasingly difficult. This prospective, multicentre study presents a systematic description of Lyme borreliosis in childhood, emphasizing epidemiological and clinical issues. Because, predominantly, inpatients were examined, Lyme neuroborreliosis was the focus of the study, with the chief concern being to minimize false-positive results. To this end, we chose to narrow the diagnostic criteria, using the presence of specific antibodies in the cerebrospinal fluid as the determining factor. The epidemiological investigation was focused on the incidence of Lyme neuroborreliosis in childhood in southern Lower Saxony as well as on the prevalence of Lyme neuroborreliosis among acute-inflammatory neurological illnesses in children. The clinical part of the study aimed at establishing criteria for differential diagnosis in addition to the detection of specific antibodies. The detection of specific IgM antibodies using an IgM capture ELISA confirmed the presence of acute Lyme borreliosis. The study examined 208 children with Lyme borreliosis, of whom 169 had Lyme neuroborreliosis, from mid-1986 until the end of 1989. The yearly incidence of Lyme neuroborreliosis in Lower Saxony was 5.8 cases/100,000 children aged 1 to 13. The manifestation index was 0.16, or one case of Lyme neuroborreliosis per 620 infected children, compared with the presence of specific antibodies against B. burgdorferi for children in the same age group and region. Both the seasonal distribution of Lyme borreliosis, which peaked in summer and autumn, as well as the information about when the tick bites took place point to an incubation period of a few weeks. The most frequent manifestation of Lyme neuroborreliosis in childhood was acute peripheral facial palsy, found in 55% of all cases (n = 93). Lyme borreliosis proved to be the most frequently verifiable cause of acute peripheral facial palsy in children, causing every second case of this disorder in summer and autumn.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗