Biomedical subjects
Publications and source records attributed to J M Trijbels.
A 3 year old mentally retarded boy with convulsions and a disturbed motor, speech and social development is presented. A persistent hyperlysinaemia, lysinuria and saccharopinuria was found. Treatment with a diet restricted in lysine seems favourable.
We present the case history of a boy, who died at the age of 3 1/2 years after a rapidly progressive neurologic disorder, characterized by psychomotor retardation, hypotonia, hemiparesis, seizures and myoclonic contractions. Histopathologic studies showed slight lipid storage in liver. Autopsy showed the characteristic features of progressive infantile poliodystrophy (Alpers' disease); ultrastructural examination showed an increased density of mitochondria in cerebral gray matter. Biochemical studies in leukocytes, cultured fibroblasts and liver indicated a deficiency in the citric acid cycle between succinate and fumarate; this deficiency was not present in muscle tissue. This study supports the view that progressive infantile poliodystrophy is associated with abnormalities in pyruvate metabolism and/or in cell mitochondria.
Three patients are described with different forms of isovaleric acidemia: a girl with the neonatal form and two brothers with an intermittent form. In all three patients the biochemical aspects are identical: Considerable amounts of metabolites of isovaleric acid, especially isovalerylglycine, are secreted with the urine. In the patients' cultured fibroblasts leucine oxydation is greatly depressed. The clinical presentation of the younger brother prompted to a direct search for a metabolic defect. After diagnosing an isovaleric acidemia in the younger brother, investigations on the presence of the same defect were performed in the elder brother too, though he did not show clinical symptoms. As a result, also isovaleric acidemia was found. It is concluded that sibs of patients with a proven inborn error of metabolism have to be studied too for the presence of the same defect. In all patients, especially in the girl with the neonatal form of isovaleric acidemia diet therapy had a beneficial effect on the further course of the disease.
Progressive infantile poliodystrophy (Alpers' disease) is associated with abnormalities in pyruvate metabolism or in cell mitochondria. A 3-year-old-boy had a severe and rapidly progressive neurologic disorder characterized by psycho-motor retardation, tetraparesis, ataxia, and myoclonic jerks, the illness being exacerbated during periods of infection. Lactate concentration in CSF was elevated. Histopathologic studies revealed lipid storage in liver and muscle. Autopsy showed a progressive infantile poliodystrophy. Mitochondrial abnormalities were found in heart muscle. Biochemical studies of muscle and liver tissue suggested a disturbance in nicotinamide adenine dinucleotide (reduced form) oxidation.
The case of a mentally retarded girl with a number of dysmorphic features, Raynaud's phenomenon, hypotonia and petit mal seizures is presented. Laboratory investigations showed alpha-aminoadipic aciduria and a high level of fetal haemoglobin. Oral L-lysine loading resulted in a marked increase of alpha-aminoadipic acid in blood and urine. After 3 months of pyridoxine medication the increase of alpha-aminoadipic acid in blood and urine during the oral L-lysine loading test was less than in the test before treatment. A normal degradation rate of DL-alpha-amino [1-14C] adipic acid in fibroblasts of the patient, as measured by 14CO2 production, did not indicate a primary enzyme defect in the alpha-aminoadipic acid transamination or decarboxylation steps. The persistent HbF could be the result of stress on the erythropoiesis by a secondary induced defect in an early stage of haemoglobin synthesis in which alpha-amino-beta-ketoadipic acid, a structural analogue of alpha-amino-adipic acid, is an intermediate.
A method is presented for the in vitro testing of the energy metabolism of human skeletal muscle. The levels of creatine phosphate, ATP, ADP and AMP, which are defined by the activity of many enzyme system, are measured after incubation of the muscle homogenate with various substrates in the presence or absence of specific inhibitors. Detection of abnormal metabolite concentrations is important for diagnosis of patients with myopathic syndromes.
This report documents the outcome of two pregnancies is a woman with phenylketonuria (PKU) who was treated with a low phenylalanine diet before conception and during pregnancy. Her first pregnancy resulted in an abortion at 17 wk. During the second pregnancy the patient was unable to maintain the right diet consistently, and her blood phenylalanine levels in the first and second trimester were elevated. This pregnancy ended in the birth of a growth retarded microcephalic infant after an amenorrhea of 42 wk. The infant has maintained a normal growth velocity below the tenth percentile, and has not shown signs of mental retardation.
An 18-month-old boy presented with general hypotonia, decreased muscle strength, retarded motor development and stunted growth. The excretion of dicarboxylic acids was enhanced. EMG was normal. A muscle biopsy revealed a lipid storage myopathy. Oral daily supplementation with 2 g D, L-carnitine resulted in: (1) an increase of the growth velocity; (2) increased muscle strength, and (3) a decrease in the lipid fraction of the fibre volume. The carnitine content of the muscle biopsied prior to treatment appeared to be normal.
The metabolism of pipecolic acid ahs been studied in three patients suffering from the cerebro-hepato-renal syndrome of Zellweger. A marked pipecolic aciduria was observed in these patients and serum levels of pipecolic acid were also elevated. From in vivo studies evidence was obtained that a disturbance in the catabolic pathway of pipecolic acid was present in all patients. This conclusion was based on the delayed return of the serum pipecolic acid concentration to the fasting concentration after oral loading of the patients with DL-pipecolic acid. Moreover, no increase in the excretion of alpha-amino adipic acid was observed in the patients after loading, in contrast with the control subjects, who showed a marked increase in the excretion of this metabolite of pipecolic acid. Further evidence for the presence of a metabolic defect in the catabolism of pipecolic acid was obtained from the observation that patients excreted significantly higher amounts of pipecolic acid during the loading experiment.
Myophosphorylase deficiency (McArdle's syndrome) is an uncommon condition characterized by exercise intolerance, muscle cramps and myoglobinuria. The present report describes the clinical, histochemical, electronmicroscopic and biochemical findings in a 12-year-old boy with myophosphorylase deficiency. The diagnosis should have been suspected when the boy was 6 years old. Most index cases have not been diagnosed until adult life, but this syndrome has to be considered in the differential diagnosis of exercise intolerance in childhood.
To obtain more information about the correct protein intake in low birth weight children, serum amino acid concentrations were determined. In 59 formula-fed, low birth weight children, serum amino acid concentrations were determined at 3, 24 and 72 h after birth and at the age of 1, 2, 3 and 4 weeks. Mean serum concentrations of all amino acids decreased during the first 24 h of life, except of aspartate and tyrosine. This decrease was followed by an increase during the first weeks of life and a variable pattern afterwards. A hypertyrosinemia (serum-tyrosine concentration > 250 mumol/l) was not found in any case. Taurine concentrations decreased gradually, as was expected because of the low taurine concentrations in cow's milk. Mean concentrations of alanine, glycine, proline and valine were higher in small for date children. Concluding, parenteral supplementation of amino acids is advisable during the first days of life to low birth weight children.
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The validity of the Wigglesworth experimental model to produce newborn rats that are small for gestational age by ligation of one of both uterine vessels was confirmed. Newborn rats from the opposite horns are used as controls in the classical model. It is concluded from this study that newborns from sham-operated dams are more satisfactory controls for newborn rats that are small for gestational age from ligated horns.
Intrauterine growth retardation was induced in rats by ligation of the artery of one of both uterine horns. Activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase in liver were measured at 0, 1, 3 and 6 h after delivery in newborn rats from normal and sham-operated litters, and from ligated and contralateral uterine horns. Lower activities of fructose-1,6-diphosphatase were found in small-for-gestational-age animals in comparison with animals from contralateral horns. When small-for-gestational-age animals were compared with animals from sham litters (which could be regarded as more satisfactory controls), the activities of two other gluconeogenic enzymes (pyruvate carboxylase and glucose-6-phosphatase) appeared to be lower as well. It is concluded that a delay in the development of these gluconeogenic enzymes could play a role in neonatal hypoglycemia in small-for-gestational-age rats.
A boy with recurrent exertional rhabdomyolysis and stunted growth is described. Fetal movements were few and the boy was small for gestational age. He always experienced easy fatigability, and he noted bouts of pigmenturia associated with episodes of considerable malaise. The change in color of the urine was caused by myoglobin. An electromyogram was myopathic. CPK rose during 60 minutes mild exercise. Prolonged moderate exercise could not be performed. Histopathological examination of muscle biopsy revealed an increase in the number of 11C fibres (20%). Electronmicroscopy revealed the wavy outline of a number of fibres and hypertrophy of sarcoplasmic reticulum elements. No cause for the stunted growth could be detected.
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