Zebra Bodies Research Articles

PRENATAL DIAGNOSIS OF GM1 -GANGLIOSIDOSIS

Abstract Amniocentesis at 14 weeks' gestation on a mother who had previously had an affected child demonstrated Type 1 GM1-gangliosidosis. β-galactosidase activity was absent in cell-free amniotic fluid (normal, 33.2 ± 16 nmoles methylumbelliferyl β-D-galactoside hydrolysed per milliliter per hour). The enzyme activity in extracts of cultured amniocytes was 1 per cent of that in normal cells. The pregnancy was terminated by hysterotomy at 17 weeks' gestation. Vacuolation and abnormal inclusions were seen by light and electron microscopy in epon-embedded sections from brain, liver, kidney and other organs. Typical zebra bodies werefound in cells of the dorsal-rootganglions. β-galactosidase activity was present but decreased in liver and brain from the affected fetus, whereas sphingomyelinase activity was increased two to six times that in controls.

The central nervous system in Fabry's disease. An ultrastructural study.

An ultrastructural study of the central nervous system (CNS) in a case of Fabry's disease revealed intraneuronal inclusions of four types in the amygdala. These included zebra bodies and granulomembranous bodies similar to those seen in Hurler's syndrome, an inclusion made of concretions of delicate membranes and amorphous material, and lipofuscin bodies. Perithelial cells throughout the nervous system contained zebra bodies and granulomem-branous bodies, as well as inclusions resembling zebra bodies on end. Endothelial cells contained myelin ovoids. The inclusions seen ultrastructurally in the CNS differed from those seen in other regions of the body.

Prenatal diagnosis of G M1 -gangliosidosis.

Amniocentesis at 14 weeks' gestation on a mother who had previously had an affected child demonstrated Type 1 GM1-gangliosidosis. β-galactosidase activity was absent in cell-free amniotic fluid (normal, 33.2 ± 16 nmoles methylumbelliferyl β-D-galactoside hydrolysed per milliliter per hour). The enzyme activity in extracts of cultured amniocytes was 1 per cent of that in normal cells. The pregnancy was terminated by hysterotomy at 17 weeks' gestation. Vacuolation and abnormal inclusions were seen by light and electron microscopy in epon-embedded sections from brain, liver, kidney and other organs. Typical zebra bodies werefound in cells of the dorsal-rootganglions. β-galactosidase activity was present but decreased in liver and brain from the affected fetus, whereas sphingomyelinase activity was increased two to six times that in controls.

Juvenile GM2 gangliosidosis. Biochemical and ultrastructural studies on a new variant of Tay-Sachs disease.

Morphological and chemical studies were performed on a cerebral biopsy in a patient with the clinical course of late infantile amaurotic idiocy. Accumulation of the Tay-Sachs ganglioside, G M2 (G 5 ) was noted in both gray and white matter. Hexosaminidase A in serum and skin fibroblast cultures was reduced to 6.6% and 12% of total hexosaminidase activity, as contrasted with 57.3% and 49.0% in controls. On electron microscopic examination there was an accumulation of intraneuronal membranous cytoplasmic bodies, zebra bodies, other varieties of lipid bodies (including aggregates of the preceding types), and lipofuscin bodies. These findings indicate that the patient had juvenile G M2 gangliosidosis, a newly recognized G M2 ganglioside storage disease in which hexosaminidase A is partially active but apparently to an insufficient degree to prevent the slow evolution of neurological symptoms.

STUDIES OF TAY-SACHS DISEASE

1) A boy aged 3 years was examined clinically and typical symptoms of Tay-Sachs disease namely, retardarion of mental and physical developments, venous types of seizures, cherry red spot in ocular fundi, decerebrated ridity at the final stage were observed.Activities of lactic dehydrogenase and of amylase in serum were elevated. EEG revealed the.electro-physiological activity was almost silent.2) Histological examination of ihe brain of the patient showed diffuse loss and marked distension of nerve cell were found all over the central nervous system, especially in the cerebrum and in the cerebellum. Abnormal fine structures resembling Membranons Cytoplasmic Bodies (Terry) and Zebra Bodies (Gonatas) were filled in the cytoplasm of nerve cells and gitter cells electron-microscopically.3) The neurochemical analysis of cerebral lipids of the brains of the case and of one another case of T-S disease revealed as follows : a) Abnormally much amount of T-S ganglioside was extracted and isolated both from the cortex and white matter of two brains by column chromatography. T-S ganglioside in case 1 was almost 70% of total ganglioside.b) The fatty acid composition, suger and sphingosine base of the T-S ganglioside isolated were determined by Gas-Liquid-Chromatography. The fatty acid was composed almost of stearic acid (C : 18). The ratio of glucose to galactose was 1 : 1. Sphingosine was C18 sphingosiue, the decrease of cerebroside varied from case to case, and small amount of gluco-kerasin was identified in them.c) The activity of β-galactosidase of the cerebral cortex in case 1 was within normal level.

The fine structure of liver in children with hurler's syndrome

Four biopsy and six autopsy specimens from livers of seven children with the classical Hurler disease, and two control liver specimens obtained at autopsy of two children with no demonstrable hepatic disease, were utilized in the present study. Tissues were obtained at both biopsy and autopsy in three patients. Our electron microscopic studies of the patients' hepatocytes showed changes of mitochondria, endoplasmic reticulum, absence of microbodies, and presence of lysosomal (autophagic) and other vacuoles. The content of the latter varied considerably. The above changes varied qualitatively and quantitatively with the progression of the disease, and ultimately, the degeneration of the hepatocytes culminated in a ghost-like appearance subsequent to the “release” of the various cytoplasmic components into the extracellular space (sinusoidal, intercellular, intrabiliary). The peribiliary dense bodies, i.e., the hepatic lysosomes, were present in the hepatocytes, but they decreased in number, as did other organelles, with the progression of the disease. The changes of the sinusoidal cells appeared to take place later and to a lesser extent than those of hepatocytes. They consisted of the presence of cytoplasmic vacuoles (largely of one type), myelin figures and, in two of the seven children, zebra bodies previously described only in nervous tissue. Myelin figures were also present, floating free in the dilated sinusoids. None of the changes found in the livers of children with Hurler syndrome were observed in controls. The various possibilities which would explain the presence of zebra bodies in reticulo-endothelial (sinusoidal) cells of the liver, and the significance of these and other findings relevant to the nature of the disease, are discussed.

An electronmicroscopical study of a case of atypical cerebral lipidosis.

Histological and electron microscopical findings in a cerebral biopsy from a 16 year old boy are presented. He developed dementia from the age of 10 and grand mal from the age of 13. The histological picture was one of neuronal lipid storage disease, and the electron microscopy, while confirming this, was not clearly characteristic of any of the previously reported lipidoses. Apart from a few “zebra bodies” (characteristics of gargoylism) the neurons contained masses of material (here called “granular vesicles”) which resembled the pericyte deposits of gargoylism, though these are very rare in the neurones of that disease. It was therefore not possible to assign a presumptive classification to this case, as there was no clinical evidence of gargoylism.