Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent around the age of three to six months of age, with the baby losing the ability to turn over, sit, or crawl. This is then followed by seizures, hearing loss, and inability to move, with death usually occurring by the age of three to five. Less commonly, the disease may occur in later childhood or adulthood. These forms tend to be less severe, but the juvenile form typically results in death by age 15.
Lysosomal storage diseases are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective due to a mutation, the large molecules accumulate within the cell, eventually killing it.
Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset.
GM2-gangliosidosis, AB variant is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. It has a similar pathology to Sandhoff disease and Tay–Sachs disease. The three diseases are classified together as the GM2 gangliosidoses, because each disease represents a distinct molecular point of failure in the activation of the same enzyme, beta-hexosaminidase. AB variant is caused by a failure in the gene that makes an enzyme cofactor for beta-hexosaminidase, called the GM2 activator.
The GM2 gangliosidoses are a group of three related genetic disorders that result from a deficiency of the enzyme beta-hexosaminidase. This enzyme catalyzes the biodegradation of fatty acid derivatives known as gangliosides. The diseases are better known by their individual names: Tay–Sachs disease, AB variant, and Sandhoff disease.
The GM1 gangliosidoses, usually shortened to GM1, are gangliosidoses caused by mutation in the GLB1 gene resulting in a deficiency of beta-galactosidase. The deficiency causes abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells, resulting in progressive neurodegeneration. GM1 is a rare lysosomal storage disorder with a prevalence of 1 to every 100,000 to 200,000 live births worldwide, although rates are higher in some regions.
Hexosaminidase is an enzyme involved in the hydrolysis of terminal N-acetyl-D-hexosamine residues in N-acetyl-β-D-hexosaminides.
N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase is an enzyme that in humans is encoded by the AGA gene.
In medical genetics, compound heterozygosity is the condition of having two or more heterogeneous recessive alleles at a particular locus that can cause genetic disease in a heterozygous state; that is, an organism is a compound heterozygote when it has two recessive alleles for the same gene, but with those two alleles being different from each other. Compound heterozygosity reflects the diversity of the mutation base for many autosomal recessive genetic disorders; mutations in most disease-causing genes have arisen many times. This means that many cases of disease arise in individuals who have two unrelated alleles, who technically are heterozygotes, but both the alleles are defective.
Cathepsin A is an enzyme that is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the CTSA gene.
Prosaposin, also known as PSAP, is a protein which in humans is encoded by the PSAP gene.
Galactosidase, beta 1, also known as GLB1, is a protein which in humans is encoded by the GLB1 gene.
GM2 ganglioside activator also known as GM2A is a protein which in humans is encoded by the GM2A gene.
Hexosaminidase A (alpha polypeptide), also known as HEXA, is an enzyme that in humans is encoded by the HEXA gene, located on the 15th chromosome.
Glycoprotein hormones, alpha polypeptide is a protein that in humans is encoded by the CGA gene.
Sphingomyelin phosphodiesterase 1 (SMPD1), also known as acid sphingomyelinase (ASM), is an enzyme that in humans is encoded by the SMPD1 gene.
Integrin beta-7 is an integrin protein that in humans is encoded by the ITGB7 gene. It can pair with ITGA4 (CD49d) to form the heterodimeric integrin receptor α4β7, or with ITGAE (CD103) to form αEβ7.
Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial is an enzyme that in humans is encoded by the DBT gene.
In molecular biology, the CHB HEX N-terminal domain represents the N-terminal domain in chitobiases and beta-hexosaminidases. Chitobiases degrade chitin, which forms the exoskeleton in insects and crustaceans, and which is one of the most abundant polysaccharides on earth. Beta-hexosaminidases are composed of either a HexA/HexB heterodimer or a HexB homodimer, and can hydrolyse diverse substrates, including GM(2)-gangliosides; mutations in this enzyme are associated with Tay–Sachs disease. HexB is structurally similar to chitobiase, consisting of a beta sandwich structure; this structure is similar to that found in the cellulose-binding domain of cellulase from Cellulomonas fimi. This domain may function as a carbohydrate binding module.
In molecular biology, glycoside hydrolase family 20 is a family of glycoside hydrolases.
