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Biomedical subjects

F Hanefeld

Publications and source records attributed to F Hanefeld.

At least 91 records · Page 5Linked to original sources
PubMed1992

L-2-hydroxyglutaric acidemia: a novel inherited neurometabolic disease.

Routine screening for organic acids revealed increased and isolated urinary excretion of L-2-hydroxyglutaric acid in 8 mentally retarded patients from five unrelated families, including three pairs of siblings. L-2-Hydroxyglutaric acid concentration was also found to be increased in the cerebrospinal fluid (CSF) and to a lesser extent in plasma. The only other biochemical abnormality was an increased concentration of lysine, both in plasma and in CSF. No organic acid abnormality was found on screening of asymptomatic family members. Patients were of either sex, and became symptomatic during childhood, with moderate to severe mental deficiency in all and definite cerebellar dysfunction in 7. Magnetic resonance imaging revealed an identical abnormal pattern with subcortical leukoencephalopathy, cerebellar atrophy, and signal changes in the putamina and dentate nuclei, in all patients. No specific biochemical function or catabolic pathway involving L-2-hydroxyglutaric acid is known in mammals, including humans. Preliminary loading and dietary studies failed to reveal the origin of the compound. The elevated CSF/plasma ratio suggests that it is in part generated within the central nervous system. This report describes a novel inherited neurometabolic disease, probably autosomal recessive, with distinct clinical, biochemical, and neuroimaging features.

Adolescent↗
PubMed1992

Multiple sclerosis in children: cerebral metabolic alterations monitored by localized proton magnetic resonance spectroscopy in vivo.

In vivo proton magnetic resonance spectroscopy of 8 children (7-16 years) with established multiple sclerosis revealed distinct alterations in regional cerebral metabolism associated with different aspects of the disease: (1) Localized proton spectra (2 to 4-ml volumes of interest) from multiple sclerosis plaques were generally characterized by a decrease in N-acetylaspartate and creatine, and an increase in cholines and myo-inositol relative to age-matched control subjects, (2) neither chronic nor enhancing plaques (by gadolinium-diethylenetriamine pentaacetic acid) during an acute exacerbation showed elevated levels of lactate or lipids, (3) spectra from adjacent white matter that did not appear suspicious in magnetic resonance images were similar to those of normal control subjects, and (4) cortical gray matter related to neighboring multiple sclerosis lesions showed a notable reduction of N-acetylaspartate. The present results show that functional impairment in multiple sclerosis is linked to gross metabolic disturbances of neuronal cell chemistry. We suggest that focal demyelination is accompanied by increased membrane precursors of proliferative turnover and is associated with secondary neuronal shrinkage or loss, perhaps extending into related cortical gray matter.

Adolescent↗
PubMed1992

Simultaneous measurement, using flow cytometry, of radiosensitivity and defective mitogen response in ataxia telangiectasia and related syndromes.

In a retrospective study, peripheral blood mononuclear cells from 13 patients with known ataxia telangiectasia (AT) (Louis Bar syndrome, McKusick #20890) were irradiated with different doses of X-rays prior to stimulation with phytohaemagglutinin. Mitogen response and cell cycle progression were assessed by two-parameter 5-bromo-2'-deoxyuridine/Hoechst--ethidium bromide flow cytometry. Compared to age-matched controls, AT cells show a severely defective mitogen response in both unirradiated and irradiated cells. Following irradiation with 1.5 Gy, AT cells exhibit significantly greater accumulations of cells in the G2 phase of the first cell cycle than controls. The ratio between the number of cells accumulated in the first cycle G2 phase and the growth fraction provides a clear distinction between AT and control cultures. In addition, two patients with microcephaly, normal intelligence, immunodeficiency, chromosomal instability and risk for lymphoreticular malignancies (Seemanová syndrome) and two patients with the Nijmegen breakage syndrome (both syndromes are listed as McKusick #25126) also exhibit very poor mitogen response and moderately increased G2 phase accumulations after X-irradiation. The simultaneous assessment of radiosensitivity and mitogen response in a single cell kinetic assay provides a speedy and accurate classification of cells of AT and AT-related syndromes.

Adolescent↗
PubMed1992

Identification of a new DMD gene deletion by ectopic transcript analysis.

The detailed genetic analysis of the Duchenne/Becker muscular dystrophy gene is hindered by the large number of exons involved and their separation by huge introns. These problems can be overcome by the analysis of mRNA rather than genomic DNA and ectopic transcripts derived from peripheral blood lymphocytes provide a convenient source of material. Using reverse transcription and nested PCR, we show here a comprehensive strategy for the rapid and complete analysis of the coding sequences from complex genes and illustrate its potential by the identification of a hitherto undescribed single exon deletion.

Base Sequence↗
PubMed1992

Multiple sclerosis in childhood.

The occurrence of multiple sclerosis (MS) in childhood is described. An increasing number of cases with onset before puberty have been published. The results of an ongoing study in Göttingen, which includes 20 patients so far are described and the potential value of childhood MS for research is stressed.

Adolescent↗
PubMed1991

Multiple sclerosis in childhood: report of 15 cases.

We report the preliminary results of an ongoing study of multiple sclerosis (MS) in childhood. The investigations include an analysis of the clinical picture and course. Multiple sclerosis in early childhood may present atypically, with a symptomatology suggesting diffuse encephalomyelitis, meningeal reaction, brain oedema, seizures, impaired consciousness and in some cases take a lethal course. Imaging studies including MRI and MR-spectroscopy, CSF-analysis, electrophysiology (VEP, BAEP, SER), and virological and immunological investigations are performed. So far 15 children have been studied. Their age at the onset of the disease ranged from 3 to 15 years. Abnormal CSF-findings with pleocytosis and oligoclonal IgG bands were present in 11 and 10 out of 15 patients respectively. MRI revealed numerous white matter lesions in the brain stem and cerebral hemispheres. VEP, BAEP and SER's were abnormal in most children. Proton magnetic resonance spectra from plaques exhibited a 50-80% decrease in N-acetyl aspartate, which is a potential marker of vital neuronal tissue, a decrease of the creatine pool and an increase of choline-containing compounds. Lactate was not increased. Our observations of MS in early childhood cast doubt on some of the previous notions concerning a latency period of several years between the exposure to a still unknown agent and the manifestation of MS. In view of atypical features in the initial phase, it would seem desirable to record cases of encephalomyelitis of undetermined origin as potential cases of MS and to register the further course for verification or exclusion.

Adolescent↗
PubMed1991

Glutaryl-coenzyme A dehydrogenase deficiency: a distinct encephalopathy.

Clinical course, diagnostic and therapeutic management, and neurodevelopmental outcome were evaluated in 11 patients with glutaryl-coenzyme A dehydrogenase deficiency. In 9 patients macrocephalus was present at or shortly after birth and preceded the neurological disease. In 7 children an acute illness resembling encephalitis appeared after a period of normal development; 2 had developmental delay and progressive "dystonic cerebral palsy." Later, all 9 displayed typical signs of a disorder of the basal ganglia. In 1 patient with macrocephalus the disorder was diagnosed before the onset of neurological disease; in another it was diagnosed prenatally. Computed tomography and magnetic resonance imaging scans revealed severe generalized cerebral atrophy, most striking in the frontal and temporal lobes in 10 patients. Further deterioration was halted after initiation of treatment consisting of low-protein diets, special formulas low in lysine and tryptophan, and supplements of riboflavin and L-carnitine. Only 1 patient showed a slight clinical improvement. Later, dietary therapy was discontinued in 2 older patients and relaxed in a third without observed adverse effects. Two patients in whom treatment could be initiated before the onset of neurological symptoms have developed normally. However, duration of follow-up (6 and 29 months) does not yet allow classification of glutaryl-coenzyme A dehydrogenase deficiency as a treatable disorder. Total body production of glutaric acid, reflected in the daily urinary output, was efficiently reduced by therapeutic measures. Levels of glutaric acid in plasma and cerebrospinal fluid remained unchanged, which may in part explain the overall unsatisfactory outcome. All patients presented with a severe secondary deficiency of carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1990

Isolated and combined deficiencies of NADH dehydrogenase (complex I) in muscle tissue of children with mitochondrial myopathies.

We describe eight children with complex I deficiency, four of them with an isolated, the other four with an additional deficiency of complex IV. Clinical, chemical and morphological findings were compared from patients with isolated and combined deficiency. In both groups, the age of onset of symptoms was between the 1st day and the 4th month of life. Clinical and biochemical heterogeneity were observed. We found no correlation between residual activity of complex I in muscle, blood lactate level, and severity of clinical symptoms. Newborns presenting with severe lactic acidosis and children with later onset myopathy were seen in both groups. The group with combined complex I deficiency showed a more severe clinical course. By light microscopy ragged red fibres were only found in two patients with combined deficiency. However, by electron microscopy structural alterations of the mitochondria were observed in six out of seven muscle specimens.

Biopsy↗
PubMed1990

[Magnetic resonance tomography of laminar heterotopia].

In one baby and 2 infants who presented with psychomotor retardation and epilepsy laminar heterotopic grey matter was demonstrated via magnetic resonance imaging. Laminar heterotopia is a rare migrational disorder with bilateral symmetric ribbons of grey matter within the centrum semiovale, separated from ventricular walls and from obviously normal-sized cortex by broad layers of white matter. The heterotopic grey matter has a signal intensity which is isointense compared with that of normal cortex irrespective of image weighting. On account of this signal behaviour differentiation against other white matter diseases is easy. The knowledge of these pathognomonic findings facilitates correct diagnosis, especially during the first and the second year of life, when signal intensities of white and grey matter differ from normal findings because of the occasionally delayed myelination process. Therefore, further diagnostic procedures can be avoided and early counseling of parents is possible.

Brain↗
PubMed1990

Peripheral facial palsy in childhood--Lyme borreliosis to be suspected unless proven otherwise.

27 consecutive cases with acute peripheral facial palsy were studied for Lyme borreliosis. In 16 out of 27 children Lyme borreliosis could be diagnosed by detection of specific IgM antibodies in CSF. CSF findings allow a clear distinction according to etiology. All children with facial palsy due to Lyme borreliosis revealed lymphocytic CSF pleocytosis, whereas in cases of unknown etiology CSF was usually normal. Bilateral facial palsy occurred only in children with Lyme borreliosis. All cases with a positive history of tick bite and/or erythema migrans in the head-neck region showed ipsilateral neurological affection suggesting a direct invasion via the affected nerve by Borrelia burgdorferi.

Adolescent↗
PubMed1989

[Lyme borreliosis--the most frequent cause of acute peripheral facial paralysis in childhood].

A prospective hospital-based multicentre study in Lower Saxony allowed to investigate the frequency of acute peripheral facial palsy due to Lyme borreliosis and its clinical and laboratory characteristics. Diagnosis of Lyme Borreliosis was based on detection of IgM antibodies against Borrelia burgdorferi in serum and CSF as well, using an IgM capture ELISA. Between June 1986 and October 1987 27 consecutive cases with acute peripheral facial palsy were studied. Lyme borreliosis is the main cause of peripheral facial palsy in childhood. It was verified serologically in two thirds of the cases. All cases with a positive history for a tick bite and/or an erythema migrans in the head-neck region showed ipsilateral neurological affection suggesting a direct invasion via the affected nerve by Borrelia burgdorferi. Peripheral facial palsy due to Lyme borreliosis represents a monosymptomatic meningoradiculitis. All children with Lyme borreliosis revealed a lymphocytic CSF pleocytosis, whereas in cases of unknown etiology CSF findings usually were normal. Therefore, in any case of facial palsy with an inflammatory CSF syndrome Lyme borreliosis has to be suspected unless proven otherwise.

Adolescent↗
PubMed1988

A new chromosomal instability disorder confirmed by complementation studies.

Two sisters with a complex clinical pattern, including microcephaly, microgenia, defects of skin pigmentation, anal stenosis/atresia, and combined immunodeficiency together with spontaneous chromosomal instability and cellular hypersensitivity to X-rays and bleomycin are described. Complementation studies on heterokaryons proved that the underlying genetic defect is non-allelic with that of patients with ataxia telangiectasia (complementation groups AB-E) and the Nijmegen breakage syndrome, but identical with the case described by Conley et al. (1986).

Ataxia Telangiectasia↗
PubMed1987

Genetic linkage study between the loci for Duchenne and Becker muscular dystrophy and nine X-chromosomal DNA markers.

A set of nine polymorphic loci defined by DNA probes was studied for linkage with the disease locus in ten families with a history of Duchenne muscular dystrophy (DMD), and three families with a history of Becker muscular dystrophy (BMD). The results confirm DMD and BMD linkage to all marker loci and suggest closer linkage of several probes than hitherto detected. This will be of practical interest for risk calculations in affected families.

Alleles↗