1/36. A two-year-old patient with an atypical expression of GM1-beta-galactosidase deficiency: biochemical, immunological, and cell genetic studies.Cultured skin fibroblasts from a 2-year-old boy with an atypical form of beta-galactosidase deficiency have been studied. With the artificial substrate 4-methylumbelliferyl-beta-D-galactopyranoside, 5--15% residual activity was found in fibroblasts from this patient. Most of this activity was in the monomeric A form of the enzyme, very little in the multimeric B form. Km value, pH profile, and heat lability of the mutant enzyme were similar to those of beta-galactosidase from control fibroblasts. Immunological studies showed that the mutant enzyme cross-reacted with an antiserum raised against human liver beta-galactosidase, but the catalytic activity per unit antigenic activity was lower than normal. It was demonstrated by somatic cell hybridization that the gene mutation in this patient is different from that in patients with type 1 or type 2 GM1-gangliosidosis. No genetic complementation was found after fusion of fibroblasts from this patient with those from two other clinical variants of GM1-gangliosidosis formerly designated type 3 and adult type 4.- - - - - - - - - - ranking = 1keywords = enzyme (Clic here for more details about this article) |
2/36. Generalized gangliosidosis type II (juvenile GM1 gangliosidosis). A pathological, histochemical and ultrastructural study.Pathological, histochemical and ultrastructural studies on 3 siblings with GM1 gangliosidosis type II are reported. These studies support a biochemical defect with profound deficiency of beta-galactosidases which results in widespread accumulation of the GM1 ganglioside and its asialo derivative in brain and to a lesser extent in viscera, as well as in storage of a keratan sulphate-like mucopolysaccharide. Striking valvular changes in the heart without myocardial involvement were seen in all cases. The histochemical and ultrastructural changes are similar to those seen in GM1 gangliosidosis type I, though less severe. Autosomal recessive inheritance without apparent ethnic predilection seems likely.- - - - - - - - - - ranking = 6.5686172840851keywords = storage (Clic here for more details about this article) |
3/36. Ultrastructural study of a muscle biopsy in a case of GM1 gangliosidosis type I.The main ultrastructural findings in a muscle biopsy from a child aged 11 months with a GM1 gangliosidosis were cytoplasmic inclusions of two different types: (1) inclusions filled with a moderate electron dense and polymorphous material thought to correspond to ganglioside accumulation and lying only in the schwann cells of intramuscular nerves. (2) Vacuolar inclusions regarded as containing polysaccharides and observed in perineurial cells, endothelium and pericytes of blood vessels, and also in muscle satellite cells. The muscle fibres only exhibited moderate and non-specific changes. The study shows that in a muscle biopsy of GM1 gangliosidosis the two characteristic types of storage deposits and their preferential localization in different cells may be demonstrated, providing that the intramuscular nerves and motor end plates are examined.- - - - - - - - - - ranking = 6.5686172840851keywords = storage (Clic here for more details about this article) |
4/36. adult (chronic) GM2 gangliosidosis. Atypical spinocerebellar degeneration in a Jewish sibship.Two adult Ashkenazi Jewish siblings have had slowly progressive deterioration of gait and posture since early childhood, distal to proximal muscle atrophy, pes cavus, foot drop, spasticity, mild ataxia of limbs and trunk, dystonic features, and dysarthria. Vision and optic fundi are normal, verbal intelligence is stable, and no seizures have occurred. The sister of the patients died at 16 years of age with the same illness. autopsy showed diffuse neuronal storage, predominating in subcortical areas, consisting of membranocytoplasmic bodies, zebra bodies, and complex lamellar structures. GM2 ganglioside was increased in her brain. hexosaminidase a was decreased in serum and leukocytes of the living patients, and was in the range for carriers of tay-sachs disease in their parents. The disease found in this family represents a new, more indolent variant of GM2 gangliosidosis.- - - - - - - - - - ranking = 6.5686172840851keywords = storage (Clic here for more details about this article) |
5/36. Molecular and clinical heterogeneity of adult GM2 gangliosidosis.adult GM2 gangliosidosis is a rare autosomal recessive disease with widely varying neurological and psychiatric manifestations. It is caused by marked deficiency, but not total absence, of beta-hexosaminidase (Hex) A, due to a single base change in the alpha-subunit gene of Hex, resulting in a substitution of Ser for Gly at position 269 in the alpha-subunit of the enzyme. The same mutation was identified in all investigated patients, most of whom are Ashkenazi jews. Among previously studied non-Jewish patients of unrelated families this mutation appears either homozygously or in compound heterozygosity with an unidentified alpha-subunit mutation, whereas all Ashkenazi patients are compound heterozygotes. In all but one of them the other mutation is one of the Ashkenazi infantile Tay-Sachs alleles, while in one 76-year-old woman with very mild neurological symptoms, it is an unidentified alpha-subunit mutation. At present, the little correlation that seems to exist between these different genotypes and the severity of the disease poses a serious dilemma for genetic counselors.- - - - - - - - - - ranking = 0.33333333333333keywords = enzyme (Clic here for more details about this article) |
6/36. Fine structure of cutaneous nerves in ganglioside storage disease.skin punch biopsies of six children suffering from infantile or late onset tay-sachs disease, juvenile sandhoff disease, or GM gangliosidosis type I, contained axons which, when viewed with the electron microscope, were distended by large amorphous black deposits. These are nonspecific residual bodies. Their large numbers indicate severe disturbance of the nerve cell and may be part of the dying back process. The three cases with tay-sachs disease had also axonal zebra or complex membranous bodies which appeared to be specific. Cytoplasmic vacuolation of other cells was a feature in the patient with GM1 gangliosidosis. Biopsies of three parents were negative.- - - - - - - - - - ranking = 92.236565826797keywords = storage disease, storage (Clic here for more details about this article) |
7/36. Hyperpigmented macules and patches in a patient with GM1 type 1 gangliosidosis.We report a case of a 10-month-old male infant with GM1 type 1 gangliosidosis who also had hyperpigmented macules and patches. light and electron microscopic findings correlated with previously published reports on findings in skin biopsy specimens of patients with lipid storage disorders. The hyperpigmented macules are most likely mongolian spots. A differential diagnosis of these lesions is discussed.- - - - - - - - - - ranking = 6.5686172840851keywords = storage (Clic here for more details about this article) |
8/36. angiokeratoma corporis diffusum in GM1 gangliosidosis, type 1.A patient with severe deficiency of beta-galactosidase, who developed skin lesions of angiokeratoma corporis diffusum between the 3rd and 10th month of life, is described. The activity of other lysosomal enzymes, including alpha-neuraminidase, was normal. The first signs of the disease were noticed during the first month of life. By 3 months coarseness of the face and psychomotor retardation were present. In addition to angiokeratoma, he had large mongolian spots and several scattered slate-blue spots of pigmentation over his body. With the exception of the skin lesions, the other clinical signs and the course of the psychomotor deterioration were within the clinical picture of GM1 gangliosidosis, Type 1. angiokeratoma, a manifestation of several lysosomal disorders, may appear in GM1 gangliosidosis during the first year of life.- - - - - - - - - - ranking = 0.33333333333333keywords = enzyme (Clic here for more details about this article) |
9/36. Enzyme activities and phospholipid storage patterns in brain and spleen samples from Niemann-Pick disease variants: a comparison of neuropathic and non-neuropathic forms.Phospholipid levels and enzyme activities were measured in brain and spleen samples from patients with the three major variants of Niemann-Pick disease. Accumulations of sphingomyelin and bis(monoacylglycero)phosphate were demonstrated in spleen from types A and B and group C Niemann-Pick disease, whereas only in type A Niemann-Pick brain was the sphingomyelin concentration increased. Sphingomyelinase activity was markedly deficient in type A Niemann-Pick brain and spleen but residual activity of approximately 12% of control was measured in type B Niemann-Pick brain. Normal or raised sphingomyelinase and beta-glucosidase activities were measured in group C Niemann-Pick brain and spleen. Significant (17% of control) residual beta-glucosidase activity was also measured in non-neuropathic Gaucher brain. Normal levels of neutral sphingomyelinase activity were measured in brain samples from the three variants of Niemann-Pick disease. Acid sphingomyelinase activity in group C Niemann-Pick brain appeared normal with respect to enzyme extraction, pH optimum (pH 5.0) and apparent Km (approximately 0.4 mmol/L). isoelectric focusing of brain sphingomyelinase revealed a degree of heterogeneity with activity peaks between pI 4.5 and 6.5. No defect was observed in group C Niemann-Pick brain and, although attenuated, all peaks were present in type B Niemann-Pick brain.- - - - - - - - - - ranking = 26.941135803007keywords = storage, enzyme (Clic here for more details about this article) |
10/36. Pathologic findings in fetal GM1 gangliosidosis.A 24-week fetus with GM1 gangliosidosis (type 1) was studied using biochemical and histopathologic methods. foam cells in viscera and placenta demonstrated widespread accumulation of a lipidlike material. By microscopy, central nervous system storage appeared confined to the retina and dorsal root ganglia, but the brain ganglioside content was measurably elevated compared with that of age-matched controls. These data, along with those of others, imply that, if the observed pathologic findings are irreversible, any attempts at intrauterine therapy must commence prior to the middle of the second trimester.- - - - - - - - - - ranking = 6.5686172840851keywords = storage (Clic here for more details about this article) |
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