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Biomedical subjects

J Jaeken

Publications and source records attributed to J Jaeken.

At least 145 records · Page 8Linked to original sources
PubMed1992

A mutation in adenylosuccinate lyase associated with mental retardation and autistic features.

We have examined the molecular basis of three cases of severe mental retardation with autistic features in one family. A point mutation in a purine nucleotide biosynthetic enzyme, adenylosuccinate lyase (ASL), segregates with the disorder. The affected children are homozygous for the point mutation while the parents and all four unaffected children are heterozygous. The point mutation is absent in control subjects. The point mutation results in a Ser413Pro substitution which leads to structural instability of the recombinant mutant enzyme, and this instability lowers ASL levels in lymphocytes. These observations suggest that the instability of ASL underlies the severe developmental disorder in the affected children, and that mutations in the ASL gene may result in other cases of mental retardation and autistic features.

Adenylosuccinate Lyase↗
PubMed1991

Radiochemical assay of adenylosuccinase: demonstration of parallel loss of activity toward both adenylosuccinate and succinylaminoimidazole carboxamide ribotide in liver of patients with the enzyme defect.

A radiochemical assay for adenylosuccinase, an enzyme which intervenes twice in the biosynthesis of adenine nucleotides, has been developed. The two substrates of the enzyme, succinylaminoimidazole carboxamide ribotide (SAICAR) and adenylosuccinate (S-AMP), were synthesized in radioactive form by incubating [2,3-14C]fumarate and, respectively, AICAR and AMP with partially purified adenylosuccinase from yeast. Enzyme activities were determined by measuring the release of labeled fumarate after its separation from the substrate by chromatography on polyethyleneimine thin-layer plates. The ratio of the activity of adenylosuccinase measured with SAICAR compared to that with S-AMP was about 1 in crude extracts of rat liver and muscle and around 0.5 in human liver. In rat and human liver, but not in rat muscle, 20 to 40% of both activities of adenylosuccinase were lost after freezing at -80 degrees C followed by thawing. In the liver of patients with adenylosuccinase deficiency, in whom the deficiency had hitherto been measured only with S-AMP, the activity of the enzyme toward S-AMP and SAICAR was found to be lost in parallel. This is in accordance with the finding that both SAICA-riboside and succinyladenosine accumulate in adenylosuccinase-deficient patients.

Adenosine Monophosphate↗
PubMed1991

Possible platelet contribution to pathogenesis of transient neonatal hyperammonaemia syndrome.

The pathogenesis of the transient neonatal hyperammonaemia syndrome is largely unknown. The role of platelet activation was investigated in three preterm infants with this syndrome by non-invasive methods. In all three infants, urinary concentrations of beta-thromboglobulin and 11-dehydrothromboxane B2 levels were much higher during the hyperammonaemia than those in ten control preterm infants. It is possible that transient platelet activation occurs in the portal system of these infants, thereby causing the hyperammonaemia.

Ammonia↗
PubMed1990

Restrictive dermopathy with distinct morphological abnormalities.

A newborn child is described with the fetal hypokinesia sequence as a consequence of a restrictive dermopathy. Remarkable findings in this infant were neonatal teeth and survival till age 4 months. Ultrastructural examination of the skin showed thin epidermis and absence of elastic fibres.

Abnormalities, Multiple↗
PubMed1990

Review: Normal and abnormal central nervous system GABA metabolism in childhood.

The metabolism and function of central nervous system GABA is briefly reviewed. Hereditary disorders of the GABA metabolism presenting in childhood are discussed with particular emphasis on the recently identified succinic semialdehyde dehydrogenase deficiency and GABA-transaminase deficiency, and on diseases associated with low CSF GABA which await further unravelling. Low CSF GABA concentrations are not always associated with convulsions. A separate section is devoted to the CSF as a tool in the diagnosis of these disorders. Finally, we present a few diagnostic and therapeutic guidelines.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

Neonatal haemochromatosis.

Four cases of neonatal haemochromatosis presenting as fulminant hepatic failure in the newborn were diagnosed by autopsy. In all four cases the diagnosis was made by histochemical demonstration of excessive iron deposition in hepatocytes and extrahepatic parenchymal cells, particularly pancreatic acinar epithelium, thyroid follicular epithelium and distal renal tubules. No haemosiderin was detectable in the extrahepatic mononuclear-phagocytic cells of the spleen, lymph nodes and bone marrow. The liver was the most severely affected organ. The hepatic haemosiderosis was associated with massive hepatocellular necrosis of prenatal onset in three patients, one of whom showed formation of regenerative nodules, establishing true congenital cirrhosis. Other inconstant findings included giant cell transformation, diffuse sinusoidal fibrosis with segregation of small groups of hepatocytes and cholestasis with pseudoacinar change of liver cell plates. The fetal liver disease had its onset in the late second trimester of pregnancy and was reflected clinically by severe panhypoproteinaemia with non-immune hydrops; hyperbilirubinaemia and haemorrhagic diatheses were apparent in the newborn. Neonatal haemochromatosis is a metabolic disorder, probably of autosomal recessive inheritance. The site and nature of the basic defect remain uncertain. Pathologists should be aware of this condition and its potential recurrence in subsequent pregnancies.

Female↗
PubMed1990

Carbohydrate deficient serum transferrin in a new systemic hereditary syndrome.

Four patients with a new, inherited, complex developmental deficiency syndrome were studied. The syndrome affects the central and peripheral nervous system, and also the retina, liver, bone, adipose tissue, and genital organs. Abnormalities of glycoproteins, glycopeptide hormones, and lipids have been found in serum from these patients, the most pronounced being increased cathodal forms of transferrin. Isoforms of serum transferrin were therefore analysed qualitatively and quantitatively by isoelectric focusing and isocratic anion exchange chromatography, and the carbohydrate composition was determined in transferrin isolated by immune affinity chromatography. All the patients had about tenfold raised serum concentrations of isotransferrins with higher isoelectric points than normal. Similar findings, though less pronounced, were made in all the fathers and in one of the mothers. Half the transferrin in the patients was constantly present in two principal abnormal cathodal forms in approximately equal amounts. Carbohydrate determinations in purified transferrin showed quantitatively similar deficiencies of sialic acid, galactose, and N-acetylglucosamine, the mannose content being normal. The results suggest that either two or all of the normally four terminal trisaccharides in transferrin may be missing. A defect in the synthesis or catabolism, or both, of this trisaccharide, which is common to many secretory glyco-conjugates, is likely. Apart from providing a quantitative diagnostic method, the present findings may serve as a basis for further studies of the metabolic deficiency in this syndrome.

Biomarkers↗
PubMed1990

[Metabolic diseases: a challenge for pediatrics].

During the past ten years we have identified in five girls a previously unreported hereditary metabolic disease with severe neurologic involvement. A common defect in the carbohydrate structure of serum glycoproteins could be demonstrated. This disease illustrates the great challenge that metabolic diseases are for pediatrics. Their number is very large and increases steadily; most of them can not yet be treated efficiently, and nearly all these disorders are hereditary. These and other features make a national and international approach necessary.

Blood Protein Disorders↗
PubMed1989

Clinical and biochemical studies in three patients with severe early infantile Cockayne syndrome.

We present clinical and biochemical data from three patients with severe Cockayne syndrome (CS) of very early onset. Unlike in classic CS, signs became evident in the first weeks of life and led to unusually early death. Fibroblasts from two of the patients showed a complete defect of the repair of UV-induced thymine dimer lesions. They were unable to remove thymine dimer lesions from their DNA, had a severe reduction of the RNA synthesis rates after UV irradiation, and showed no reactivation of an UV-inactivated indicator gene and no DNA recondensation after UV irradiation. DNA repair investigated in these two fibroblast cell strains resembled that of xeroderma pigmentosum cells of complementation group A. In contrast, fibroblasts from the third patient showed the same in vitro repair characteristics as classic CS cells.

Cell Survival↗