1/12. Enzyme studies in GM2 gangliosidiosis, and their application in prenatal diagnosis.Assay of hexosaminidase a and B enzymes in four cases with developmental regression and cherry red spot on fundus examination confirmed that three cases had tay-sachs disease, and one case had sandhoff disease. prenatal diagnosis was carried out by hexosaminidase enzyme assay in amniotic fluid and cells in one family, and chorionic villus sample in the second family. The fetus was diagnosed to be unaffected in one, and affected in the other family. Assay of hexosaminidase a and B is useful for specific diagnosis of GM2 gangliosidosis, and for prenatal diagnosis to reduce the burden of these disorders.- - - - - - - - - - ranking = 1keywords = cherry (Clic here for more details about this article) |
2/12. Ptosis in late infantile tay-sachs disease.The brief communication describes a 2-year-old child who presented with delayed achievement and regression of milestones, seizures of multiple types, exaggerated response to sound, inability to see and bilateral cherry red spots. In addition to these typical manifestations of the late infantile variety of tay-sachs disease, unilateral ptosis was present. The magnetic resonance imaging of brain revealed abnormalities consistent with an advanced stage of the disease.- - - - - - - - - - ranking = 1keywords = cherry (Clic here for more details about this article) |
3/12. Tay Sachs disease: an autopsy case report.This report describes a case report of a postmortem performed on a 5-year old patient of tay-sachs disease, presenting with failure to thrive, muscular flaccidity, and cherry-red spots on macula on fundoscopy. There was no history of similarly affected sibling or any other family member. The diagnosis was confirmed by enzyme studies. At postmortem, there was no organomegaly. The brain, on microscopy, showed vacuolated swollen neurons.- - - - - - - - - - ranking = 1keywords = cherry (Clic here for more details about this article) |
4/12. tay-sachs disease with conspicuous cranial computerized tomographic appearances.An autopsy case of a 3-year-old female infant with tay-sachs disease was presented. A cherry red spot in the fundus and a deficiency of N-acetyl-beta-hexosaminidase a in the white blood cells were revealed soon after admission at the age of one year. Her parents and sister were found to be healthy carriers. The patient showed a typical clinical course with marked cranial swelling. In addition to the marked ballooning of neurons on light microscope, membranous cytoplasmic body (MCB) on electron microscope and abnormal accumulation of GM2 ganglioside in the cerebral cortex by thin layer chromatography were confirmed in the autopsy specimens. In the late stage of her clinical course, the cranial computerized tomography (CT) demonstrated symmetric and deep-wavy hyperdense cerebral cortical zones, diffuse hypodensity and diminished volume of cerebral white matter, mild to moderate ventricular dilatation, and a small cerebellum and brainstem. These conspicuous appearances of the cranial CT seem to be characteristic of tay-sachs disease in the late stage, and they are derived from abnormal accumulation of GM2 ganglioside in the cerebral cortex, and diffuse intense demyelination (dysmyelinating demyelination) of the cerebral white matter.- - - - - - - - - - ranking = 1keywords = cherry (Clic here for more details about this article) |
5/12. tay-sachs disease: B1 variant.This first child of non-Jewish parents had nystagmus at 4 months of age, bilateral cherry-red macular spots at 7 months of age, and hyperacusis at 8 months of age; the patient has deteriorated progressively following a clinical course typical of tay-sachs disease B variant. Total beta-N-acetylhexosaminidase assayed with 4-methylumbelliferyl-beta-glucosamine (4 MU GlcNAc) as substrate was within the normal range in plasma and cultured dermal fibroblasts and 2/3 the normal mean in leukocytes. The hexosaminidase a activity, assayed with the same substrate in plasma and cultured fibroblasts, approximated tay-sachs disease heterozygote levels; however, the activity of hexosaminidase a assayed with 4 MU Glc NAc-6-sulfate in the plasma, leukocytes, and cultured fibroblasts was less than 8, 2, and 1%, respectively of the control mean. This female infant with the B1 variant of tay-sachs disease demonstrated an earlier onset and more rapidly progressive course than was observed in 4 of the 5 previously reported patients with this tay-sachs disease variant.- - - - - - - - - - ranking = 1keywords = cherry (Clic here for more details about this article) |
6/12. GM1 gangliosidosis: clinical and laboratory findings in eight families.GM1 Gangliosidosis is an autosomal recessive genetic disorder due to deficiency of the lysosome enzyme beta-galactosidase, with consequent tissue accumulation of glycolipids, oligosaccharides, and especially GM1 ganglioside. In the present paper we report the clinical and laboratory findings obtained for eight families starting from eight index cases exhibiting the childhood form of the disease. The total number of cases in these families may be as high as 14, thus causing GM1 gangliosidosis to be the inborn metabolic error most frequently diagnosed in our service. Hypotonia, neuromotor retardation, hepatosplenomegaly, macrocephaly, and hydrocele are some of the most frequent clinical findings. The disease evolves towards convulsions and bronchopneumonia, leading to patient death generally during the first half of the second year of life. The presence of vacuolated lymphocytes, alterations of the lumbar vertebrae, and cherry spots on the retina were observed in almost all patients. When tested for inborn metabolic errors, all patients gave normal results, a fact that may have confused and delayed diagnosis. Diagnosis was made by urine oligosaccharide chromatography and confirmed by beta-galactoside measurement in peripheral blood leukocytes. This method proved to be accurate also for the detection of heterozygotes, which permitted post-mortem diagnosis in two families. The authors speculate that increased fetal loss and tendency towards macrosomy may be possible characteristics of the disease, suggest that testing for vacuolated lymphocytes be used as a screening method, and propose that urine oligosaccharide chromatography be included in the routine screening for inborn metabolic errors.- - - - - - - - - - ranking = 1keywords = cherry (Clic here for more details about this article) |
7/12. The cherry-red spot in Tay-Sachs and other storage diseases.The disappearance of the cherry-red spot in an otherwise typical patient with tay-sachs disease is described and illustrated. This clinical observation has rarely been made, but it is consistent with the pathological finding of loss of retinal ganglion cells. Disappearance of the cherry-red spot has also been observed in GM1 generalized gangliosidosis, the sialidoses known as the cherry-red spot-myoclonus syndrome and the Goldberg syndrome, and Niemann-Pick, type C disease. Thus the absence of a cherry-red spot in the neurologically impaired child or adult does not exclude these diagnoses.- - - - - - - - - - ranking = 8keywords = cherry (Clic here for more details about this article) |
8/12. Thermal activation of hexosaminidase a in a genetic compound with tay-sachs disease.Increase in total hexosaminidase activity has been observed during heat treatment of serum and leukocyte specimens from a 1-year-old boy with cherry-red spot and severe and progressive mental and motor deterioration. The activity increased 40% in the first 40-70 min of incubation at 50 degrees C and pH 4.3, but declined thereafter and was only slightly above the initial activity in the final 2-3 h of incubation. Heat treatment of specimens from family members revealed very reduced rates of inactivation of hexosaminidase in the proband's father and some paternal relatives, whereas those of the mother and some maternal relatives were indistinguishable from those of Tay-Sachs carriers. Mixing experiments with enzyme preparations from the proband, normal controls and patients with tay-sachs disease resulted in additive values and did not support the possibility of inhibitor- or activator-related defect. Fractionation of heat-treated samples by ion exchange chromatography and electrophoresis, as well as examination of the separated fractions for their thermostability, have shown that hexosaminidase a is the activated component and hexosaminidases B, I1 and I2 are not affected. These findings suggest that the patient is a genetic compound and the apparent thermal activation is probably due to formation of hexosaminidase a from altered alpha-subunits produced by the paternal mutant alpha-allele and beta-subunits produced by the normal beta-alleles.- - - - - - - - - - ranking = 1keywords = cherry (Clic here for more details about this article) |
9/12. Ultrastructural pathology of skin biopsy and fibroblast enzyme studies in a case of GM2-gangliosidosis with deficient hexosaminidase a and thermolabile hexosaminidase b.A 2 year-old non-Jewish boy had muscle hypertonia, a black cherry spot, dementia, and seizures. His skin biopsy showed membranous cytoplasmic bodies in axonal terminals and zebra body-like inclusions in schwann cells. Biochemically, a deficiency of Hex A and two separate Hex B peaks indicated a type 1 (B variant, Tay Sachs) like subvariant of GM2-gangliosidosis.- - - - - - - - - - ranking = 1keywords = cherry (Clic here for more details about this article) |
10/12. The AB-variant of GM2-gangliosidosis. Clinical, biochemical, and pathological studies of two patients.Clinical, neuropathological, and biochemical studies are reported in two children with the AB-variant of GM2-gangliosidosis. One patient had become symptomatic by 1--1.5 years, initially showing cerebellar signs, and then progressive psychomotor retardation, with hypotonia, spasticity, dementia, and macular cherry red spots, until death at the age of 4.5 years. The second patient showed an earlier onset of retardation and a more rapidly progressive course. At postmortem, the brains were of normal or near normal weights and displayed grossly only mild cerebral cortical and cerebellar atrophy, and mild pallor or attenuation of the white matter. Neuronal storage was widespread throughout the CNS, and both neurons and glia contained a variety of abnormal, membranous inclusions. Visceral organs were not involved. Ganglioside sialic acid was increased several fold in gray matter, with GM2 the predominant ganglioside species. N-acetyl-beta-glucosaminidase activities in serum, leukocytes, fibroblasts, and postmortem gray matter, assayed with an artificial, fluorogenic substrate, were normal, as were activities of other lysosomal hydrolases.- - - - - - - - - - ranking = 1keywords = cherry (Clic here for more details about this article) |
| | Next -> |