Neonatal cardiomyopathy and lactic acidosis responsive to thiamine

A congestive cardiomyopathy was diagnosed in a girl at the age of 4 weeks. In the weeks following she developed general muscle hypotonia and plasma lactate increased to 8.5 mmol/L. Biochemical investigations of a muscle biopsy at the age of 3 months showed a deficiency in the oxidation of all substrates tested: pyruvate plus malate, 2-ketoglutarate and palmitate plus malate. After freezing and thawing of the homogenate and the addition of essential cofactors, the oxidation of the ketoacids normalized. The oxidation defect in the untreated homogenate can be explained by a deficiency in one of the cofactors (such as thiamine pyrophosphate, NAD+ or CoASH), or by a defect in the oxidative phosphorylation. Treatment with thiamine and carnitine resulted in a decrease in blood lactate to normal levels and a dramatic clinical improvement. Suspension of thiamine caused deterioration of her clinical condition and lactic acidaemia. The thiamine therapy was then continued. The girl is now 6 years old and in perfect health

Neuroblastoma stage 4S: Tumor regression rate and risk factors of progressive disease

Background: The clinical course of neuroblastoma stage 4S or MS is characterized by a high rate of spontaneous tumor regression and favorable outcome. However, the clinical course and rate of the regression are poorly understood. Methods: A retrospective cohort study was performed, including all patients with stage 4S neuroblastoma without MYCN amplification, from two Dutch centers between 1972 and 2012. We investigated the clinical characteristics, the biochemical activity reflected in urinary catecholamine excretion, and radiological imaging to describe the kinetics of tumor regression, therapy response and outcome. Results: The cohort of 31 patients reached a 10-year overall survival of 84% ± 7% (median follow-up 16 years; range, 3.3-39). During the regressive phase, liver size normalized in 91% of the patients and catecholamine excretion in 83%, both after a median of two months (liver size: range, 0-131; catecholamines: range, 0-158). The primary tumors completely regressed in 69% after 13 months (range, 6-73), and the liver architecture normaliz

Two-dimensional electrophoresis of urinary mucopolysaccharides on cellulose acetate after f-cetylpyridiniumchloride (CPC) precipitation: A method suitable for the routine laboratory

A technique for two-dimensional electrophoresis of urinary mucopolysaccharides (MPS) is described. The method allows differentiation of a number of mucopolysaccharidoses and is suitable for application in the routine laboratory. This technique should be used to evaluate urines from patients who have a positive MPS-spot test and/or an increased urinary excretion of MPS-bound uronic acid. Urinary MPS excretion patterns are given from normal individuals, patients with the Sanfilippo syndrome and the Hunter syndrome

Inborn errors of pyrimidine degradation: clinical, biochemical and molecular aspects

The pyrimidines, uracil and thymine, are degraded in four steps. The first three steps of pyrimidine catabolism, controlled by enzyme shared by both pathways, result in the production of the neurotransmitter amino acid beta-alanine from uracil and the nonfunctional (R)-(-)-beta-aminoisobutyrate from thymine. The fourth step is controlled by several aminotransferases, which have different affinities for beta-alanine, beta-aminoisobutyrate and GABA. Defects concerning the first three steps all lead to a reduced production of beta-alanine; defects of the transaminases involving the metabolism of beta-alanine and GABA lead to accumulation of these neurotransmitter substances. In addition, other metabolites will accumulate or be reduced depending on the specific enzyme defect. Analysis of the abnormal concentrations of these metabolites in the body fluids is essential for the detection of patients with pyrimidine degradation defects. Clinically these disorders are often overlooked because symptomatology is highly aspecific. The growth in our knowledge concerning inborn errors of pyrimidine degradation has emphasized the importance of the clinical awareness of these defects as a possible cause of neurological disease and a contraindication for treatment of cancer patients with certain pyrimidine analogues. The various defects are discussed and attention is paid to clinical genetic and diagnostic aspect

Prolidase deficiency diagnosed by 1H-NMR spectroscopy of urine

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