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Biomedical subjects

H Mandel

Publications and source records attributed to H Mandel.

At least 73 records · Page 4Linked to original sources
PubMed1994

A new type of peroxisomal disorder with variable expression in liver and fibroblasts.

We describe two siblings, presently 5 and 9 years of age, who had neurodegenerative symptoms after the first year of life. Although they lacked clinical characteristics of a peroxisomal disorder, they had elevated levels of plasma very long chain fatty acids, pipecolic and phytanic acids, and abnormal bile acid intermediates, which suggested a generalized peroxisome deficiency disorder. Immunocytochemical study and electron microscopy of the liver disclosed absence of peroxisomes in approximately 90% of hepatocytes. However, the remaining 10% of the hepatocytes had numerous normal-looking peroxisomes containing catalase activity and catalase antigen. Alanine glyoxylate aminotransferase and the peroxisomal beta-oxidation enzymes acyl-coenzyme A oxidase and 3-ketoacyl coenzyme A thiolase were also present in the organelles. Both cell types were grouped in clusters. In contrast to most of the liver cells, fibroblasts cultured from skin biopsy specimens had normal peroxisomal functions. Thus this defect in peroxisome biogenesis is characterized by variable expression in different tissues (liver vs fibroblasts), as well as within individual cells in the same tissue (liver mosaicism). Awareness of the heterogeneity in tissue expression of peroxisomal disorders could be of critical importance in prenatal diagnosis.

Child↗
PubMed1993

Congenital muscular dystrophy with neurological abnormalities: association with Hirschsprung disease.

We report on a baby girl with congenital muscular dystrophy (CMD) with neurological abnormalities ("CMD Plus" condition), who also had Hirschsprung disease. This association may indicate a category of congenital muscular dystrophy with involvement of the visceral nervous system. We propose that Hirschsprung disease be added to the list of anomalies pertaining to the "CMD Plus" array, and that CMD should be considered when Hirschsprung disease occurs with central nervous system anomalies.

Brain↗
PubMed1993

Human liver pathology in peroxisomal diseases: a review including novel data.

Results from electron microscopic morphometry, enzyme cytochemistry and immunolocalization in liver biopsies are reviewed. Emphasis is put on the following aspects: 1) relationship between peroxisomal size and enzyme concentration; 2) abnormal enlargement of peroxisomes in many congenital disorders with peroxisomal dysfunction; 3) normal localization of matrix enzymes in several patients with peroxisomal dysfunction, with the exception of catalase, which is mainly cytoplasmic; 4) ghost-like peroxisomes in the liver of several syndromes but not in nine cases labelled as Zellweger; 5) discrepancies between liver and cultured fibroblasts; 6) trilamellar, regularly spaced inclusions, large stacks of which are birefringent, indicate a peroxisomal dysfunction; their absence does not exclude it. The same rule holds for lipid in macrophages which is insoluble in acetone and n-hexane (after fixation). The chemical nature of these two storage materials remains unclear; and 7) proliferation of human peroxisomes is frequent in acquired liver diseases and drug toxicity, but is never accompanied by an increase in size, in contrast to the effect of the fibrates and phthalates in rat and mouse. Novel data from seven peroxisomal patients are included.

Adrenoleukodystrophy↗
PubMed1993

Muscle involvement in Walker-Warburg syndrome. Clinicopathologic features of four cases.

Walker-Warburg syndrome is a lethal autosomal recessive disorder characterized by anomalies of the central nervous system and the eye. Recently, elevation of muscle enzymes and congenital muscular dystrophy have been found to contribute to the diagnosis of this syndrome. The authors studied two pairs of siblings with Walker-Warburg syndrome, offspring of consanguineous parents from two unrelated families. The patients had hydrocephalus, congenital glaucoma, elevated muscle enzymes, and hypotonicity. The histologic and ultrastructural muscular changes were consistent with congenital muscular dystrophy.

Brain↗
PubMed1993

Mucolipidosis III presenting as a rheumatological disorder.

Genetic disorders of the osseous skeleton constitute a challenging area of differential diagnosis. Three patients, 2 girls and 1 boy, were referred to our pediatric rheumatology clinic because of progressive stiffness of their hands and flexion contractures of fingers, accompanied by additional musculoskeletal changes. One of the girls had been diagnosed in early childhood as having juvenile rheumatoid arthritis, the other was suspected to have scleroderma, and the boy had been labelled with "Hurler's syndrome." On evaluation, all 3 patients had the clinical and roentgenographic features of mucolipidosis III; the diagnosis of mucolipidosis III was confirmed by enzymatic assays. We call for an awareness of pediatricians, rheumatologists and orthopedic surgeons to the "rheumatological" presentation of mucolipidosis III. The establishment of a precise diagnosis will lead to adequate management and will allow appropriate genetic counseling.

Arthrography↗
PubMed1992

Plasma lipoproteins and monocyte-macrophages in a peroxisome-deficient system: study of a patient with infantile refsum disease.

Hypocholesterolaemia in infantile Refsum disease (IRD) may link peroxisomes and lipoprotein metabolism. In our patient, plasma cholesterol levels were reduced to 26% and 29% of control in LDL and HDL fractions, respectively. Plasma apolipoproteins B-100 and A-I levels were 52% and 66% of controls, respectively. In the kindred, plasma cholesterol concentration was 61-73% of controls. The HDL-cholesterol/apo A-I ratios were: patient 0.12; kindred 0.17; controls 0.28. Analysis of the IRD patient's lipoprotein revealed compositional abnormalities in all fractions. The patient's LDL demonstrated a substantial reduction in its lipid-to-protein ratio. Alterations in plasma lipoproteins affect their interaction with macrophages. Upon incubation of the patient's LDL with J-774 macrophages, its cellular uptake, measured as cholesterol esterification rate, was only 66% of a control rate. The abnormal LDL of the IRD patient showed also only 25% of control susceptibility to in vitro oxidation. Studies of cellular cholesterol metabolism in the patient's monocyte-derived macrophages (MDM) showed 57% increased cholesterol esterification rate in comparison to normal MDM. The possible link between lipoprotein abnormalities and monocyte-macrophage cholesterol metabolism is discussed.

Animals↗
PubMed1992

Infantile refsum disease: gastrointestinal presentation of a peroxisomal disorder.

This article describes two siblings with infantile Refsum disease (IRD) whose initial presentation was that of malabsorption and mimicked a-beta- or homozygous hypo-beta-lipoproteinemia. Failure to recognize IRD in the first-born child precluded proper genetic counseling and prenatal diagnosis in subsequent pregnancies and also caused considerable delay in diagnosing IRD in the second child. The clinical heterogeneity of peroxisomal disorders constitutes a diagnostic challenge, which demands a high degree of awareness from the part of the clinician. This is particularly the case with IRD, where protracted diarrhea with low serum cholesterol levels appears to be a frequently occurring initial feature during the 1st months of life.

Abetalipoproteinemia↗
PubMed1991

Glutaric aciduria type I. Brain CT features and a diagnostic pitfall.

Serial CT findings in an infant with glutaric aciduria type I (GA-I) are reported. The major CT features were dilatation of the insular cisterns, regression of the temporal lobes, with "bat wings" dilatation of the Sylvian fissures and hypodensity of the lenticular nuclei. CT changes preceded the onset of symptoms by 3 months. An improvement in the temporal lobe atrophy was seen after a period of treatment, coinciding with marked clinical improvement. A peculiar feature was the presence of external hydrocephalus, which diverted the attention from manifestations of the primary disease and thus constituted a diagnostic pitfall. The delineation and recognition of the characteristic radiologic manifestations of GA-I are essential for allowing an adequate radiologist/clinician interaction in diagnosing this inborn error of metabolism.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

Walker-Warburg syndrome with microtia and absent auditory canals.

Walker-Warburg syndrome is a lethal, autosomal recessive disorder characterized by anomalies of the central nervous system and eye. Typical findings include hydrocephalus, agyria, retinal dysplasia, cerebellar dysgenesis, anterior chamber dysgenesis, and encephalocele. Recently, the phenotypic spectrum has been expanded to include congenital muscular dystrophy. Two sibs with Walker-Warburg syndrome are reported. One sib had congenital glaucoma and hydrocephalus. The other sib had hydrocephalus, microtia, absent auditory canals, and pale retinas, barely within the phenotypic spectrum of the disorder. Elevation of muscle enzymes was consistent with the diagnosis of Walker-Warburg syndrome.

Abnormalities, Multiple↗
PubMed1990

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: biochemical studies and family investigation of four generations.

3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) lyase activity was determined by the recently described spectrophotometric method of Wanders et al. (1988a) in polymorphonuclear leukocytes and lymphocytes obtained from 33 members of a highly consanguineous Arab-Bedouin family belonging to four generations. Seven subjects were obligatory heterozygotes (parents and grandparents of three propositi); in seven additional subjects enzyme activity in both cell types was in the heterozygote range. No asymptomatic homozygotes were found. The results support the proposed autosomal recessive mode of inheritance of this disorder.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

Determination of fructose metabolic pathways in normal and fructose-intolerant children: a 13C NMR study using [U-13C]fructose.

An inborn deficiency in the ability of aldolase B to split fructose 1-phosphate is found in humans with hereditary fructose intolerance (HFI). A stable isotope procedure to elucidate the mechanism of conversion of fructose to glucose in normal children and in HFI children has been developed. A constant infusion of D-[U-13C]fructose was given nasogastrically to control and to HFI children. Hepatic fructose conversion to glucose was estimated by examination of 13C NMR spectra of plasma glucose. The conversion parameters in the control and HFI children were estimated on the basis of doublet/singlet values of the plasma beta-glucose C-1 splitting pattern as a function of the rate of fructose infusion (0.26-0.5 mg/kg per min). Significantly lower values (approximately 3-fold) for fructose conversion to glucose were obtained for the HFI patients as compared to the controls. A quantitative determination of the metabolic pathways of fructose conversion to glucose was derived from 13C NMR measurement of plasma [13C]glucose isotopomer populations. The finding of isotopomer populations of three adjacent 13C atoms at glucose C-4 (13C3-13C4-13C5) suggests that there is a direct pathway from fructose, by-passing fructose-1-phosphate aldolase, to fructose 1,6-bisphosphate. The metabolism of fructose by fructose-1-phosphate aldolase activity accounts for only approximately 50% of the total amount of hepatic fructose conversion to glucose. It is suggested that phosphorylation of fructose 1-phosphate to fructose 1,6-bisphosphate by 1-phosphofructokinase occurs in human liver (and intestine) when fructose is administered nasogastrically; 47% and 27% of the total fructose conversion to glucose in controls and in HFI children, respectively, takes place by way of this pathway. In view of the marked decline by 67% in synthesis of glucose from fructose in HFI subjects found in this study, the extent of [13C]glucose formation from a "trace" amount (approximately 20 mg/kg) of [U-13C]fructose infused into the patient can be used as a safe and noninvasive diagnostic test for inherent faulty fructose metabolism.

Blood Glucose↗
PubMed1989

Clinical zinc deficiency during zinc-supplemented formula.

A 2 1/2-month old preterm infant had failure to gain weight with high caloric intake, and had generalized persistent dermatitis and mild diarrhea. The patient was being fed zinc-supplemented cow's-milk-based formula (Osterfeed). High caloric intake of 8 weeks' and topical treatment of 11 weeks' duration were futile. A thorough investigation revealed low serum zinc concentration. Administration of zinc sulfate 150 mg/day resulted in brisk weight gain and complete clearing of skin lesions. The infant maintained normal levels of zinc 4 months after zinc therapy was discontinued, while being fed unmodified cow's milk and a diet of corn flour. The probability that zinc-supplemented formulas do not meet the high zinc requirements of premature infants is raised. The importance of plasma or serum zinc examination in preterm infants with slow growth velocity or failure to gain weight despite adequate caloric intake, with or without skin lesions and diarrhea, is emphasized.

Body Weight↗
PubMed1989

Sandifer syndrome reconsidered.

Three children with Sandifer syndrome are described. One patient was at first erroneously diagnosed as having neurological disease; the two others had true neurological damage, which led initially to misinterpretation of their bizarre dystonic features. Awareness of this entity will spare such children needless investigations and suffering, while giving them the benefit of proper treatment.

Antacids↗