Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of adult type mucolipidosis with beta-galactosidase and sialidase deficiency is described. This patient, a woman aged 20, had mental retardation, macular cherry-red spots, corneal clouding, gargoyle-like face, cerebellar ataxia, myoclonus and convulsions beginning at the age of 14. Bony deformities, vacuoles in the peripheral lymphocyte and foamy cells in the bone marrow were also noted. Biopsy study of the sural nerve and vermiform appendix disclosed many vacuoles in almost every kind of cells, although the accumulated substance in these vacuoles could not be characterized histochemically or ultrastructurally. Deficient leukocyte beta-galactosidase and sialidase were confirmed. There was increased urinary sialoglycopeptide and increased siliac acid and hexosamine in the glycoprotein of lymphocytes. Leukocytes sialidase activites of the parents were 30 to 50% of the control values. These results suggest a genetic defect of sialidase.
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PMID:Adult type mucolipidosis with beta-galactosidase and sialidase deficiency. Histological and biochemical studies. 9 67

The carbohydrate-deficient glycoprotein syndrome is a newly described hereditary disorder which may be due to a defect in the glycoprotein metabolism. Predominant symptoms are mental retardation, epilepsy, cerebellar ataxia, polyneuropathy, squint, retinitis pigmentosa, retarded growth, hypothyroidism and liver steatosis. Increased serum glycoprotein-deficient transferrin is a marker of the disease and confirms the diagnosis. We describe four Norwegian children with this syndrome. Olivopontocerebellar degeneration was found upon examination of the brain in two patients who died.
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PMID:[The carbohydrate deficient glycoprotein syndrome]. 1044 Oct 90

The carbohydrate-deficient glycoprotein syndrome is a newly recognised genetic disorder characterised by mental retardation, liver disfunction during infancy, cerebellar ataxia and atrophy, polyneuropathy, growth retardation, stroke-like episodes, and the appearance of carbohydrate-deficient fractions of multiple glycoproteins in the serum. The neuroradiological findings have been known as features of olivopontocerebellar atrophy. However, whether the abnormalities in the cerebellum and brain stem progress after birth is not known. We have carried out serial CT and MRI on three Japanese patients with this syndrome at different ages. A small cerebellum, with peculiar enlargement of the cisterna magna, and a small brain stem are present in infancy and atrophy of the anterior vermis and from before backwards in the cerebellar hemispheres seem to progress throughout early childhood.
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PMID:Neuroradiological findings in the carbohydrate-deficient glycoprotein syndrome. 747 67

A new group of metabolic disorders, the carbohydrate-deficient glycoprotein (CDG) syndromes, is reviewed with emphasis on the key condition, the CDG syndrome type I. This disease, an autosomal-recessive multisystem condition, has now been diagnosed in 45 Scandinavian patients. It is characterized by carbohydrate deficiencies of a number of glycoproteins, including uniform changes in transferrin. The transferrin alterations provide a distinct biologic marker and a practical and simple laboratory diagnostic means employing analysis of serum or blood spots from Guthrie-type filter paper. The syndrome presents differently through various life periods. A four-stage grouping system by age has been constructed and is presented. During infancy, internal organ symptoms are dominant; some may be life-threatening. In later childhood and adolescence, static mental deficiency, cerebellar ataxia, slowly progressive lower limb neuropathy, and pigmentary retinal degeneration, as well as secondary skeletal deformities, are the most prominent findings. Two very recently described clinical and biologic variants, CDG syndromes II and III, are summarized and compared to CDG type I.
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PMID:Carbohydrate-deficient glycoprotein syndromes: peculiar group of new disorders. 821 37

Carbohydrate-deficient glycoprotein (CDG) syndrome is a newly recognized hereditary disorder that presents with psychomotor retardation, cerebellar ataxia, peripheral sensorimotor neuropathy, and, variably, skeletal abnormalities, lipodystrophy, and retinitis pigmentosa. These abnormalities appear to be produced by a defect that causes reduced carbohydrate content in glycoproteins. We studied seven patients with CDG type I belonging to five unrelated families. The concentration of serum TBG, a glycoprotein of hepatic origin, was measured by RIA and T4 saturation and was found to be below the normal range in three of the seven patients and normal in four of them. More than half of the total serum TBG had reduced sialic acid content and localized on isoelectric focusing (IEF) as two prominent bands cathodal to the three major bands of normal TBG. The latter two bands are responsible for the characteristic IEF pattern or CDG syndrome. TBG in patients with CDG had immunoreactivity indistinguishable from that of normal TBG and had normal affinity for T4, T3, and rT3. Serum total T4, T3, and rT3 were below the normal range in seven, five, and seven patients, respectively. The free T4 index was also below normal in four patients, but the free T4 concentration, measured by equilibrium dialysis at low dilution, and serum TSH were in the midnormal range. The serum total T4 and rT3 levels were disproportionately reduced relative to the serum TBG concentration and compared to the concentrations of these iodothyronines in matched subjects with inherited partial TBG deficiency. Chronic illness cannot explain these changes, because, contrary to patients with nonthyroidal illness, those with CDG had significantly higher serum total T3/T4 and lower rT3/T4 ratios. It is concluded that IEF of TBG is a rapid and simple method for the diagnosis of CDG type I and that the abnormal pattern can be detected as early as 5 days postpartum. Patients with CDG are chemically euthyroid, and it is postulated that the reduction in serum iodothyronine concentrations beyond that explained on the basis of low TBG levels may be due to the interference with binding to TBG by an unidentified substance.
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PMID:Thyroid function tests and characterization of thyroxine-binding globulin in the carbohydrate-deficient glycoprotein syndrome type I. 853 Jun 28

Voltage-gated sodium channels are glycoprotein complexes responsible for initiation and propagation of action potentials in excitable cells such as central and peripheral neurons, cardiac and skeletal muscle myocytes, and neuroendocrine cells. Mammalian sodium channels are heterotrimers, composed of a central, pore-forming alpha subunit and two auxiliary beta subunits. The alpha subunits form a gene family with at least 10 members. Mutations in alpha subunit genes have been linked to paroxysmal disorders such as epilepsy, long QT syndrome, and hyperkalemic periodic paralysis in humans, and motor endplate disease and cerebellar ataxia in mice. Three genes encode sodium channel beta subunits with at least one alternative splice product. A mutation in the beta 1 subunit gene has been linked to generalized epilepsy with febrile seizures plus type 1 (GEFS + 1) in a human family with this disease. Sodium channel beta subunits are multifunctional. They modulate channel gating and regulate the level of channel expression at the plasma membrane. More recently, they have been shown to function as cell adhesion molecules in terms of interaction with extracellular matrix, regulation of cell migration, cellular aggregation, and interaction with the cytoskeleton. Structure-function studies have resulted in the preliminary assignment of functional domains in the beta 1 subunit. A sodium channel signaling complex is proposed that involves beta subunits as channel modulators as well as cell adhesion molecules, other cell adhesion molecules such as neurofascin and contactin, RPTP beta, and extracellular matrix molecules such as tenascin.
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PMID:Sodium channel beta subunits: anything but auxiliary. 1148 43

Voltage-gated Na+ channels are glycoprotein complexes responsible for initiation and propagation of action potentials in excitable cells such as central and peripheral neurons, cardiac and skeletal muscle myocytes, and neuroendocrine cells. Mammalian Na+ channels are heterotrimers, composed of a central, pore-forming a subunit and two auxiliary beta subunits. The a subunits form a gene family with at least 10 members. Mutations in alpha subunit genes have been linked to paroxysmal disorders such as epilepsy, long QT syndrome, and hyperkalaemic periodic paralysis in humans, and motor endplate disease and cerebellar ataxia in mice. Three genes encode Na + channel beta subunits with at least one alternative splice product. A mutation in the beta1 subunit gene has been linked to generalized epilepsy with febrile seizures plus type 1 (GEFS+1) in a human family with this disease. Na+ channel beta subunits are multifunctional. They modulate channel gating and regulate the level of channel expression at the plasma membrane. More recently, they have been shown to function as cell adhesion molecules in terms of interaction with extracellular matrix, regulation of cell migration, cellular aggregation, and interaction with the cytoskeleton. Structure-function studies have resulted in the preliminary assignment of functional domains in the beta1 subunit. A Na+ channel signalling complex is proposed that involves beta subunits as channel modulators as well as cell adhesion molecules, other cell adhesion molecules such as neurofascin and contactin, RPTPbeta, and extracellular matrix molecules such as tenascin.
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PMID:Beta subunits: players in neuronal hyperexcitability? 1177 42

Homozygous variants in MAG, encoding myelin-associated glycoprotein (MAG), have been associated with complicated forms of hereditary spastic paraplegia (HSP). MAG is a glycoprotein member of the immunoglobulin superfamily, expressed by myelination cells. In this study, we identified a novel homozygous missense variant in MAG (c.124T>C; p.Cys42Arg) in a Portuguese family with early-onset autosomal recessive cerebellar ataxia with neuropathy and oculomotor apraxia. We used homozygosity mapping and exome sequencing to identify the MAG variant, and cellular studies to confirm its detrimental effect. Our results showed that this variant reduces protein stability and impairs the post-translational processing (N-linked glycosylation) and subcellular localization of MAG, thereby associating a loss of protein function with the phenotype. Therefore, MAG variants should be considered in the diagnosis of hereditary cerebellar ataxia with oculomotor apraxia, in addition to spastic paraplegia.
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PMID:Novel MAG Variant Causes Cerebellar Ataxia with Oculomotor Apraxia: Molecular Basis and Expanded Clinical Phenotype. 3234 Feb 15