Lysosomal Storage Diseases Overview

An inherited metabolic disorder caused by a deficiency in the enzyme hexosaminidase A, leading to the accumulation of GM2 ganglioside in the brain and other tissues.

A genetic defect in the HEXA gene, which codes for the alpha subunit of hexosaminidase A, leading to a deficiency in the enzyme.

A rare genetic condition that causes a deficiency in both hexosaminidase A and hexosaminidase B enzymes, due to a defect in the beta subunit which is shared by both.

A type of lysosome that is abnormally swollen and contains a buildup of undegraded material, specifically GM2 ganglioside, in conditions like Tay-Sachs disease.

The second step in the degradation of gangliosides, specifically the breakdown of GM2 ganglioside.

An enzyme that breaks down GM2 ganglioside, a type of lipid found in the brain and other tissues.

An enzyme that breaks down GM2 ganglioside, but also has a different role in breaking down other types of lipids.

A protein that helps hexosaminidase A function properly by acting as a mediator in the degradation of GM2 ganglioside.

A group of genetic disorders characterized by the accumulation of specific macromolecules within lysosomes due to defects in degradative enzymes. This accumulation leads to progressive damage in various tissues and organs, often affecting the central nervous system.

A treatment approach for LSDs that aims to replace the missing or defective enzyme, allowing for the breakdown of accumulated substrates. It involves administering the enzyme through regular infusions.

A treatment approach for LSDs that involves introducing small molecules that help the faulty enzyme fold correctly and reach its destination within the cell. These chaperones can bypass the blood-brain barrier and offer potential for treating the central nervous system involvement.

An X-linked lysosomal storage disease caused by a deficiency in the enzyme α-galactosidase A, leading to the accumulation of globotriaosylceramide (Gb3) in various tissues and organs.

A group of lysosomal storage diseases caused by deficiencies in sphingomyelinase, resulting in the accumulation of sphingomyelin in various tissues, particularly the brain and liver.

A lysosomal storage disease characterized by a deficiency in arylsulfatase A, leading to the accumulation of sulfatides in the nervous system and other tissues.

A group of inherited disorders where harmful quantities of lipids (fats) build up in cells, causing health problems.

Treatment used to reduce the amount of harmful substances (substrate) in the body, aimed at slowing down disease progression.

A lysosomal storage disease where glucosylceramide builds up, causing liver, spleen, and bone marrow enlargement.

A type of Niemann-Pick disease that affects infants and leads to severe neurodegeneration and early death.

A type of Niemann-Pick disease with later onset, usually leading to survival into adulthood.

A type of Niemann-Pick disease characterized by a defect in lipid transport, causing neurological issues, and is more common than types A and B.

A critical symptom of Niemann-Pick disease type A and B, where the macula of the eye appears abnormally red.

Fabry disease is an X-linked genetic disorder caused by a deficiency in the enzyme alpha-galactosidase A. This deficiency leads to the buildup of a fatty substance called globotriaosylceramide (Gb3) in various organs, including the kidneys, heart, and nervous system. This buildup causes a range of symptoms.

The second step in the degradation of globoside involves the removal of a galactose residue from the molecule by the enzyme alpha-galactosidase A. This step is crucial for the proper breakdown and recycling of glycolipids, which are important components of cell membranes.

Gaucher disease is a genetic disorder characterized by a deficiency in the enzyme glucocerebrosidase. This deficiency leads to the accumulation of glucocerebroside, a fatty substance, in macrophages, which are immune cells.

The accumulation of glucocerebroside in macrophages causes these cells to swell and become known as Gaucher cells. These Gaucher cells are abnormal and can lead to various symptoms, including anemia, easy bruising, and hepatosplenomegaly (enlarged liver and spleen).

Enzyme replacement therapy (ERT) is a standard treatment for Gaucher disease. This therapy involves replacing the missing or deficient glucocerebrosidase enzyme, allowing for the breakdown of accumulated glucocerebroside.

The 'crumpled tissue paper' appearance of the cytoplasm of Gaucher cells is caused by the presence of numerous enlarged, elongated lysosomes filled with glucocerebroside. These lysosomes, which normally break down cellular waste, are overloaded in Gaucher disease and give the characteristic appearance.

Migalastat is a chaperone therapy approved for Fabry disease that helps improve the function of some mutant alpha-galactosidase A enzymes. It works by promoting the correct folding and stability of the enzyme.

Fabry, Gaucher, and Pompe are all lysosomal storage disorders. These disorders occur due to genetic mutations that affect the function of specific lysosomal enzymes, leading to the accumulation of undegraded substrates within lysosomes and causing cellular damage.