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Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Oncocytic tumours are characterised by hyperproliferation of mitochondria. We immunohistochemically analysed all enzymes of the oxidative phosphorylation system in 19 oncocytic thyroid tumours. A specific lack of complex I was detected, which was expressed at <5% of the level determined in surrounding non-cancerous tissue. [ABSTRACT FROM AUTHOR]

Previously, renal cell carcinoma tissues were reported to display a marked reduction of components of the respiratory chain. To elucidate a possible relationship between tumourigenesis and alterations of oxidative phosphorylation, we screened for mutations of the mitochondrial DNA (mtDNA) in renal carcinoma tissues and patient-matched normal kidney cortex. Seven of the 15 samples investigated revealed at least one somatic heteroplasmic mutation as determined by denaturating HPLC analysis (DHPLC). No homoplasmic somatic mutations were observed. Actually, half of the mutations presented a level of heteroplasmy below 25%, which could be easily overlooked by automated sequence analysis. The somatic mutations included four known D-loop mutations, four so far unreported mutations in ribosomal genes, one synonymous change in the ND4 gene and four nonsynonymous base changes in the ND2, COI, ND5 and ND4L genes. One renal cell carcinoma tissue showed a somatic A3243G mutation, which is a known frequent cause of MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episode) and specific compensatory alterations of enzyme activities of the respiratory chain in the tumour tissue. No difference between histopathology and clinical progression compared to the other tumour tissues was observed. In conclusion, the low abundance as well as the frequently observed low level of heteroplasmy of somatic mtDNA mutations indicates that the decreased aerobic energy capacity in tumour tissue seems to be mediated by a general nuclear regulated mechanism. [ABSTRACT FROM AUTHOR]

Abstract 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 (C 15:0, C 17:0, C 17:1) 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. [ABSTRACT FROM AUTHOR]

Unlabelled: Trimethoprim-sulphamethoxazole (TMP-SMZ) is considered a safe drug for treatment of infectious bacterial diseases in children. Side-effects are rare and generally take the form of a hypersensitivity reaction to the sulphamethoxazole component of the drug. Hepatic injury usually presents as a transient elevation of liver enzymes, which is of little clinical relevance. Fulminant liver failure due to TMP-SMZ has been reported in only six adults and never in children. We here report a 5-year-old girl who developed fulminant liver failure 3 weeks after her third exposure to TMP-SMZ. After a biphasic clinical course she underwent successful liver transplantation.Conclusion: Trimethoprim-Sulphamethoxazole may cause fulminant liver failure in children. The disease can run a biphasic clinical course and liver transplantation must be considered as the therapeutic option for these patients. [ABSTRACT FROM AUTHOR]

Unlabelled: Veno-occlusive disease was diagnosed in an 18-month-old boy who had regularly consumed a herbal tea mixture since the 3rd month of life. The boy developed portal hypertension with severe ascites. Histology of the liver showed centrilobular sinusoidal congestion with perivenular bleeding and parenchymal necrosis without cirrhosis. The tea contained peppermint and what the mother thought was coltsfoot (Tussilago farfara). The parents believed the tea aided the healthy development of their child. Pharmacological analysis of the tea compounds revealed high amounts of pyrrolizidine alkaloids. Seneciphylline and the corresponding N-oxide were identified as the major components by thin-layer chromatography, mass spectrometry and NMR spectroscopy. We calculated that the child had consumed at least 60 micrograms/kg body weight per day of the toxic pyrrolizidine alkaloid mixture over 15 months. Macroscopic and microscopic analysis of the leaf material indicated that Adenostyles alliariae (Alpendost) had been erroneously gathered by the parents in place of coltsfoot. The two plants can easily be confused especially after the flowering period. The child was given conservative treatment only and recovered completely within 2 months.Conclusion: In all cases of veno-occlusive disease pyrrolizidine alkaloids ingestion should be excluded. The identity of collected plant material should be verified by pharmaceutically trained experts and information of composition, dosage and mode of administration should be included in guidelines for herbal preparations. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rechtsmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The cascade of known haematopoietic growth factors controlling granulomonopoiesis and erythropoiesis includes interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (EPO). Elevated endogenous IL-3 and IL-6 cord blood levels in infection-free premature and mature neonates may reflect their possible role for expansion of haematopoietic progenitor cells, granulocytes and monocytes. Within the erythroid lineage a synergistic action of IL-3, IL-6 and EPO can be assumed. To identify the regulatory role in fetal haematopoietic expansion cord blood plasma levels of these haematopoietic growth factors were assessed in 19 premature and 20 mature infants using commercial enzyme-linked immunosorbent assay and enzyme-amplified sensitivity immuno assay test kits. Peripheral blood IL-3, GM-CSF and EPO were studied in 5 and 10 premature infants respectively. Compared with cord blood levels we found a decline in EPO levels but no decrease of IL-3 and GM-CSF during the 1st month of life. We conclude that postnatal decrease in plasma burst-promoting activity levels in preterm infants is mainly explained by low postnatal EPO levels. [ABSTRACT FROM AUTHOR]

In six patients with mitochondrial (encephalo-) myopathy investigations of skeletal muscle revealed a defect of pyruvate dehydrogenase complex (PDHC) in combination with one or more respiratory chain complex deficiencies. A combination of defects of this kind has not been reported previously. Five of the six patients presented within the 1st year of life and had a severe clinical course. Intrafamilial variability of the clinical course in dizygotic twins both suffering from a cytochrome c oxidase deficiency and one of them also from a PDHC deficiency suggests an additional effect of PDHC deficiency on the clinical symptoms. Immunoblot studies of PDHC in five of the patients revealed no abnormalities in their subunit pattern, rendering a defect of mitochondrial protein import or assembly unlikely. The finding of a combined PDHC and respiratory chain deficiency has implications for the diagnostic approach, for therapy and genetic counselling. The exact pathogenetic mechanism of this combination of defects remains to be elucidated. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The diagnosis of infantile sialic acid storage disease (ISSD) was established in two siblings on the basis of typical clinical signs and the biochemical findings of hyperexcretion and intracellular storage of free sialic acid. A severe, steroid resistant nephrosis occurred in both siblings. The activities of lysosomal enzymes, including sialidase, were normal. A combined detection method for sialic acids with Limax flavus agglutinin labelling and phosphotungstic acid staining showed severely alterated sialic acid components in epithelial kidney cells and indicate a causal relationship between the nephrosis and the underlying biochemical defect. Further observations of ISSD patients with renal involvement will prove if a separate nephropathic phenotype exists. [ABSTRACT FROM AUTHOR]

An infant with moderate muscular hypotonia and congenital lactic acidosis died suddenly at the age of 3 months. Autopsy revealed no abnormalities responsible for this unexpected death. Measurement of mitochondrial enzymes involved in energy production indicated a severely decreased total pyruvate dehydrogenase complex (PDHC) activity in muscle tissue (0.23 nmoles x min-1 x mg protein-1, control range 2.8-8.7) and moderately decreased PDHC activity in fibroblasts (0.27 nmoles x min-1 x mg protein-1, control range 0.37-2.32). The activity of the first component E1 (pyruvate dehydrogenase) in muscle tissue was 10 times lower than that of controls (0.008 nmoles x min-1 x mg protein-1, control range 0.10-0.25). The activities of dihydrolipoyl dehydrogenase (E3) and various other mitochondrial enzymes were normal. Immunochemical analysis in skeletal muscle tissue and fibroblasts demonstrated a decrease in the amount of the alpha and beta subunits of E1. The features of this patient are compared with those of other patients reported in the literature with immunochemically confirmed combined E1 alpha and beta deficiency. [ABSTRACT FROM AUTHOR]

An infant with moderate muscular hypotonia and congenital lactic acidosis died suddenly at the age of 3 months. Autopsy revealed no abnormalities responsible for this unexpected death. Measurement of mitochondrial enzymes involved in energy production indicated a severely decreased total pyruvate dehydrogenase complex (PDHC) activity in muscle tissue (0.23 nmoles · min · mg protein, control range 2.8-8.7) and moderately decreased PDHC activity in fibroblasts (0.27 nmoles · min · mg protein, control range 0.37-2.32). The activity of the first component E (pyruvate dehydrogenase) in muscle tissue was 10 times lower than that of controls (0.008 nmoles · min · mg protein, control range 0.10-0.25). The activities of dihydrolipoyl dehydrogenase (E) and various other mitochondrial enzymes were normal. Immunochemical analysis in skeletal muscle tissue and fibroblasts demonstrated a decrease in the amount of the α and β subunits of E. The features of this patient are compared with those of other patients reported in the literature with immunochemically confirmed combined E α and β deficiency. [ABSTRACT FROM AUTHOR]

A patient with severe muscular hypotonia, failure to thrive, a metabolic acidosis and a renal tubular dysfunction is presented. The disease followed a fatal course. Blood lactate and pyruvate levels as well as lactate/pyruvate ratios were strongly elevated. There were a massive excretion of lactate in urine, a generalized hyperaminoaciduria, a proteinuria and a mellituria. The carnitine concentration was diminished in blood and muscle tissue. Biochemical investigations of skeletal muscle and liver tissue revealed a defect in the respiratory chain at the level of succinate: cytochrome c oxidoreductase. The defect could not be demonstrated in cultured fibroblasts. [ABSTRACT FROM AUTHOR]

Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Unlabelled: Inspiratory stridor of unknown origin was the leading clinical symptom in an 11-month-old boy. The stridor increased over a period of 4 weeks, and assisted ventilation became necessary. Selective urinary screening by gas chromatography/mass spectrometry analysis revealed excretion of ethylmalonic and 3-OH-isovaleric acid and of N-isobutyryl-, N-2-methylbutyryl-, N-isovaleryl-, N-hexanoyl- and N-suberylglycine. Neither hypoglycaemia nor metabolic acidosis were noticed. Treatment with 200 mg of riboflavin per day led to a dramatic clinical improvement with restoration of normal respiration and an increase in muscular tone within 2 months. During this period, metabolite excretion in urine completely normalized. Riboflavin-sensitive multiple acyl-CoA dehydrogenation deficiency was confirmed in cultured fibroblasts. With riboflavin supplementation, the development of the child has been favourable, with normal school attendance now at an age of 9 years.Conclusion: As respiratory symptoms might precede other symptoms in disorders of mitochondrial oxidation, we propose determination of urinary organic acids in all cases of unexplained laryngeal stridor. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Platelet Transfusion Can Mimic Somatic mtDNA Mutations" published in the December 2005 issue.

Comprehensive data on 30 patients with propionic acidaemia, diagnosed by selective screening for inborn errors of metabolism, are presented. The most valuable diagnostic metabolites found were methylcitric-, 3-hydroxypropionic-, and 2-methyl-3-oxovaleric acids. Hyperlysinaemia and hyperlysinuria are also characteristic findings in this disease. The metabolic pattern found in propionic acidaemia is discussed extensively as are enzymatic findings. Residual activity of propionyl-CoA carboxylase is neither a predictive marker for severity nor for outcome of the disease. Propionate fixation assay were less reliable for confirmation of propionic acidaemia and of no prognostic value. Clinical presentation of the disease is discussed in detail. Besides the well-known unspecific findings (poor appetite, feeding difficulties, vomiting, dehydration, weight loss, muscular hypotonia, dyspnoea, somnolence, apathy, convulsion, coma, severe metabolic acidosis, hyperammonaemia) various skin abnormalities have been detected in about 50% of all patients. In 27% 'dermatitis acidemica' was found. [ABSTRACT FROM AUTHOR]