1/81. prenatal diagnosis of GM1-gangliosidosis: biochemical manifestations in fetal tissues. A prenatal diagnosis of GM1-gangliosidosis was made in a pregnancy at risk, on the basis of a deficiency of beta-galactosidase activity demonstrated in cultured amniotic fluid cells. Biochemical analyses were performed in the aborted fetus. GM1-ganglioside beta-galactosidase activity was reduced to 1% of the control value in both the brain and liver of the affected fetus. Lamellar bodies suggestive of membranous cytoplasmic bodies were found in cells of basal ganglions, while the accumulation of GM1-ganglioside in the brain was not remarkable. ( info) |
2/81. 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. ( info) |
3/81. Infantile sialidosis: a phenocopy of type 1 GM1 gangliosidosis distinguished by genetic complementation and urinary oligosaccharides. A clinical description of an apparently classical case of type 1 GM1 gangliosidosis is presented. The patient was the first-born child of first cousins. She was diagnosed at 6 weeks and died at 6 months. beta-galactosidase activity was deficient in cultured fibroblasts using [3H]GM1 ganglioside and [3H]ceramide-lactose as substrates. Genetic complementation studies performed after cell fusion between cultured fibroblasts from the patient and from two other type 1, one type 2, and one juvenile GM1 gangliosidosis strain were positive with all strains. Subsequent studies revealed an increased excretion of a sialic acid-containing hexasaccharide in the patient's cells. parents' fibroblasts contained normal levels of beta-galactosidase. The case emphasizes the variability of the clinical expression in sialidosis and the importance of demonstrating a primary gene defect in establishing a diagnosis of an inborn error or metabolism. ( info) |
4/81. Infantile GM1-gangliosidosis with marked manifestation of lungs. GM1-gangliosidosis is a disease characterized by abnormal accumulation of GM1-ganglioside in the brain and viscera. The disease is characterized by clinical findings similar to Hurler's disease and pathologic features resembling Niemann-Pick's disease but with involvement of the glomerular epithelium. A 14-month-old boy, clinically diagnosed as GM1-gangliosidosis, died of respiratory insufficiency and was autopsied except for the brain. Biochemically, marked increase of GM1-ganglioside in the viscera was demonstrated. Pathologically, the foam cells were present in the viscera. Some parts of the cytoplasmic vacuoles in the lungs and spleen contained osmiophilic fibrillar material electron-microscopically. This case was characterized by marked accumulation of foam cells in the pulmonary alveolar spaces. ( info) |
5/81. 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. ( info) |
6/81. 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. ( info) |
| adult GM2 gangliosidosis is a rare disorder that often presents with both neurological and psychiatric syndromes. Effective treatment of the psychotic and affective symptoms associated with this disorder has been complicated by poor treatment response and the concern that many psychotropic agents may worsen the underlying gangliosidosis. We report the successful use of electroconvulsive therapy for treatment of severe depression in a young man with adult GM2 gangliosidosis. ( info) |
8/81. GM2-gangliosidosis, AB variant: clinico-pathological study of a case. Clinical and neuropathological studies of a case of AB variant GM2-gangliosidosis have been presented. The patient was a 14 months old black female infant who had "black cherry spot" in the retinas. The total activities of beta-galactosidase and N-acetyl-beta-hexosaminidase, as well as the proportion of hexosaminidase a and B components in her serum and leukocytes were normal when the assays were carried out with artificial fluorogenic substrate. Diagnosis of GM2-gangliosidosis AB variant was established by an abnormal increase of GM2-ganglioside in the biopsied brain tissue, similar to classical tay-sachs disease. Her clinical manifestation appeared to be similar but somewhat milder than those of classical tay-sachs disease. light microscopic features of the cerebral biopsy were also closely similar to tay-sachs disease and sandhoff disease but gliosis and neuronal loss were less pronounced. Electron microscopic study revealed numerous membranous cytoplasmic bodies (MCB) and zebra bodies in neurons. In addition, varieties of large intracytoplasmic inclusions in astrocytes, a feature distinctly different from classical tay-sachs disease, were observed. Numerous cytoplasmic inclusions were also present in oligodendroglia, pericytes and microglial cells. ( info) |
9/81. 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. ( info) |
| A 42 year old man presented with a slowly progressive gait disturbance, generalised weakness, dysarthria, clumsiness and tremor of his hands, and involuntary jerks. hexosaminidase a activity in plasma, leucocytes and fibroblasts was considerably reduced, establishing the diagnosis of GM2 gangliosidosis. Clinical examination showed two previously unreported features, a clinically evident sensory neuropathy and internuclear ophthalmoplegia. ( info) |