Biomedical subjects
Publications and source records attributed to W Sperl.
Diatoms in the bone marrow (femur) of 16 nondrowned bodies were detected by a modern method of ultrafiltration. The rate of diatoms were found to be in the same range as in cases of drowning. The results deny the proof of diatoms even in bone marrow to be useful any longer for the diagnosis of death from drowning.
UNLABELLED: In patients with propionic acidaemia (PA), the increased intracellular concentration of propionyl-CoA leads to a relative abundance of odd-numbered long-chain fatty acids (OLCFAs) in body lipids. We investigated the relative amount of OLCFA in erythrocyte membrane lipids over a period of 1-8 years in five patients with early onset PA and present their clinical outcome. After extraction from erythrocyte membrane lipids and esterification, fatty acids were analysed by capillary column gas chromatography. The sum of the OLCFA 15- and 17- carbon saturated and 17-carbon monounsaturated fatty acids (C15:0, C17:0, C17:1) was calculated and expressed as a percentage of the total C14-C22 fatty acids in the sample. Three patients (pccBC-complementation group) presented with a stable clinical course and showed OLCFA values usually below 1.9% (median % +/- SD: 1.4+/-0.5, 1.6+/-0.5, 1.8+/-0.5). Two patients (pccA-complementation group) had a more severe course of the disease and showed higher medians and a broader range of OLCFA levels (2.2+/-1.2 and 2.2+/-0.8). CONCLUSION: Our study shows that odd-numbered long-chain fatty acid concentrations are increased in patients with propionic acidaemia and are higher in those with a more severe clinical course. The value of odd-numbered long-chain fatty acids in the assessment of the phenotypic severity and in the management of propionic acidaemia remains to be proven in a prospective long-term study with more patients of differing phenotype.
Menkes' disease is a rare X-linked multisystemic lethal disorder of copper transport metabolism. Failure of synthesis of several copper enzymes explains most of the clinical features, which were characterised by neurodegenerative symptoms and connective tissue manifestations. Most cases are still prone to rapidly progressive cerebral degeneration and early death in the first few years. Since CNS-dysfunction usually preceeds development of the pathognomonic "steely" hair, delay of clinical diagnosis and onset of therapeutic intervention precludes longlasting neurological benefit. This is particularly true for patients with large deletions or severe truncations of the responsible ATP7A gene. We report on our own experience with a patient, who was diagnosed to be affected by Menkes' syndrome at the age of one year, due to the specific hair texture and biochemical abnormalities. Molecular investigation revealed a total deletion of exon 15 of the ATP7A gene. Heterozygosity was confirmed by means of real-time PCR in the child's mother, but could be excluded in the grandmother and other female relatives at risk. Therapeutic support with subcutaneous injection of copper-histidinate normalised diminished copper and coeruloplasmin serum levels, but was unable to influence the clinical course and to prevent the fatal outcome at the age of two years. This observation is in line with the experience of the literature claiming that currently available medication will hardly be able to normalise brain copper levels. However, observations of clinical variants of Menkes' disease with quite a different outcome and, more importantly, emerging of alternative copper transport pathways might still justify this time-limited therapeutic intervention.
Subacute necrotizing encephalomyelopathy (SNE; Leigh's disease), though a defined entity in neuropathological and morphological terms, is characterized by high clinical heterogenity. SNE of infancy can be defined and diagnosed on the basis of clinical symptoms more readily than juvenile and adult forms. Four patients with SNE displayed combinations of recurrent vomiting, difficulty in swallowing, failure to thrive, impairment of ocular innervation, muscle tone regulation and central regulation of respiration. These symptoms, particularly in combination, point to a disorder of the brainstem and basal ganglia. In addition, all four patients were suffering from lactic acidosis. Other possible indicators, but not in all 4 patients, were abnormal CT brain scans, impaired nerve conduction velocity, elevated CSF protein levels and enlarged mitochondria in muscle cells. Abnormal brainstem auditory evoked potentials have proved to be one of the best criteria for early diagnosis of brainstem lesions. Enzyme assays of pyruvate degradation in cultured skin fibroblasts revealed diminished activity of the pyruvate dehydrogenase complex in one patient (52 pmol/mg protein x min; median range 313, 82-917, n: 58). This paper summarizes the findings and proposes primary and secondary criteria of assistance in establishing an initial clinical diagnosis of infantile SNE. As no common pathogenetic mechanisms have yet been recognized and no uniform diagnostic markers are yet available, the diagnosis still requires confirmation by histological examination of brain and brainstem, as was the case with all four patients presented.
We report a child with a rare cardiac involvement in GM1 gangliosidosis. At the age of 9 months a secondary dilatative cardiomyopathy due to the metabolic disorder was diagnosed. During 2 years the functional echocardiographic signs became normal, though the ECG still was not normal. Our report is the first longterm observation and investigation of cardiac involvement in GM1 gangliosidosis.
Defects in the branched chain amino acid metabolism are the most common forms of organic aciduria. Two thirds of the cases manifest themselves during the neonatal period, most of them with an acute onset. Prompt diagnosis of organic acidurias is a task of the pediatrician and the neonatologist and depends on their early identification of children with suspect clinical symptoms. Between 1984 and 1987 9 patients presented with an organic aciduria at the Pediatric Department of the University of Innsbruck, 7 of them were neonates. 4 of these 7 children had a defect in the branched chain amino acid metabolism, 3 with propionic acidemia, one with maple syrup urine disease. The remaining 3 children presented with lactic aciduria. In all our patients diagnosis was performed by combined gas chromatography and mass spectrometry of spontaneous urine samples. Diagnostic procedures and therapeutic measures applied in the acute metabolic crisis are presented. Continuous arteriovenous hemofiltration has been found to be an efficient method for eliminating toxic metabolites in intractable metabolic acidosis.
BACKGROUND: Rett syndrome can be diagnosed only clinically. Several biochemical abnormalities are known, but none of them is characteristic. To our knowledge only one study on carnitine deficiency and one case of successful carnitine therapy have been reported. PATIENT: A five years old girl with normal milestones in the first months of life became retarded in the second year with muscle hypotonia of unknown cause and loss of known abilities. Later on recurrent washing movements of the hands, hyperventilation and microcephaly were observed and the diagnosis of Rett syndrome was established. METHOD: A muscle biopsy was performed for the determination of enzymes of the respiratory chain and polarographic respirometry in permeabilized muscle fibres at the age of 3 1/2 years. Carnitine in plasma and urine was determined before and during a therapy with carnitine. RESULTS: The activities of some enzymes of the respiratory chain were slightly decreased as was oxygen consumption in the permeabilized muscle fibres. However muscle morphology and histochemistry were normal. With normal carnitine in the muscle plasma carnitine was clearly decreased but showed a normal ratio of acylcarnitine to free carnitine. Carnitine substitution was started at the age of 3 1/2 years with 75 mg/kg/day and was later increased to 150 mg/kg/day. The treatment showed not only a normalisation of plasma carnitine but also an improvement of physical activity, muscle hypotonia, communication and sleep time. A wash out for one month and resumption of therapy confirmed the efficacy of this regime. CONCLUSIONS: The reason for the carnitine deficiency in the patient with Rett syndrome is not known. A primary carnitine deficiency is excluded by normal muscle carnitine. An explanation for the efficacy of the carnitine therapy is not known, although one could speculate that carnitine provides a transport system for acetyl groups, stimulates acetylcholine formation in the brain and in this way improves the disturbance of the cholinergic system.
Propionic acidemia (PA) is one of the most frequent organic acidurias, but information on the outcome of individuals with PA is rather limited. We present data of 49 patients with PA, which were gathered from 18 metabolic centers throughout Central Europe on the occasion of an international workshop. All patients were identified by selective metabolic screening, and 86% of them were classified as having early-onset PA owing to their presentation with clinical symptoms within the first 90 days of life. Mortality rate was one third, and details of symptoms and treatment of the surviving patients are discussed. The great variation of phenotypic expression of the disease and different therapeutic strategies (especially in regard to the degree of protein restriction) used at the various institutions involved in this study imply the need for a registry of PA patients and for a multicenter prospective treatment study.