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General Disease Information
Fabry Disease : General Disease Information
The enzyme involved in Fabry disease is α-galactosidase A (α-GAL A). The substrate that accumulates in Fabry disease is globotriaosylceramide (GL-3, also known as Gb3). This website will use α-GAL and GL-3 to refer to the enzyme and substrate, respectively, involved with Fabry disease.
Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called α-galactosidase A (α-GAL A, referred to here as α-GAL). The primary biological function of α-Gal is to degrade specific lipids in lysosomes, including globotriaosylceramide (referred to here as GL-3, also known as Gb3). Lipids that can be degraded by the action of α-Gal are called “substrates” of the enzyme. Reduced or absent levels of α-GAL activity leads to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, and skin. This accumulation of GL-3 is believed to cause the various symptoms of Fabry disease, including pain, kidney failure, and increased risk of heart attack and stroke.
Fabry disease is an X-linked recessive genetic disorder that affects both men and women. Most individuals with Fabry disease have missense mutations in the GLA gene. Missense mutations can alter the structure of α-GAL, which results in the accumulation of the enzyme in a part of the cell called the endoplasmic reticulum (ER). As a result of the accumulation of α-GAL in the ER, the enzyme is unable to reach the lysosome, the part of the cell where α-GAL does its work of breaking down substrate.
It is currently estimated that Fabry disease affects approximately 5,000 to 10,000 people worldwide. However, several literature reports suggest that Fabry disease may be significantly under diagnosed, and the prevalence of the disease may be much higher.
Pompe Disease : General Disease Information
Pompe disease is also known as glycogen storage disease type II (GSD-II) and acid maltase deficiency.
Pompe disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called acid α-glucosidase (GAA). The role of GAA within the body is to break down glycogen, the form of sugar stored in living cells for use as energy. Reduced or absent levels of GAA activity leads to the accumulation of glycogen in the affected tissues, including the heart, skeletal muscles (including those involved with breathing), liver, and nervous system. This accumulation of GAA is believed to cause progressive muscle weakness and respiratory insufficiency in individuals with Pompe disease.
Pompe disease is an autosomal recessive genetic disorder that affects both males and females, and can occur in infants, toddlers, or adults. The prognosis varies according to the time of onset and severity of symptoms. It is estimated that Pompe disease affects approximately 5,000 to 10,000 people worldwide.
Gaucher Disease : General Disease Information
Inherited genetic mutations in the GBA1 gene, which encodes for the glucocerebrosidase (GCase) enzyme, are the cause of Gaucher disease. Over the last decade, GBA1 mutations have also been identified as the most common genetic risk factor for Parkinson's.
Gaucher disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called β-glucocerebrosidase (GCase). The role of GCase within the body is to break down a complex fatty substance called glucocerebroside. Reduced or absent levels of GCase activity leads to the accumulation of glucocerebroside in the affected tissues, including the spleen, liver, lungs, bone marrow, and sometimes in the brain. This accumulation of GCase is believed to cause the various symptoms of Gaucher disease, including an enlarged liver and spleen, skeletal disorders, and, in some instances, lung, kidney, and central nervous system impairment. Individuals with Gaucher disease may also bruise easily and experience pain and fatigue due to anemia and low blood platelets.
It is estimated that Gaucher disease affects approximately 8,000 to 10,000 people worldwide. Gaucher disease is an autosomal recessive genetic disorder that affects both men and women. Most individuals with Gaucher disease have missense mutations in the GBA gene. Missense mutations can alter the structure of GCase, which results in the accumulation of the enzyme in a part of the cell called the endoplasmic reticulum (ER). As a result of the accumulation of GCase in the ER, the enzyme is unable to reach the lysosome, the part of the cell where GCase does its work.
Gaucher-Parkinson’s Disease Link
Inherited genetic mutations in the GBA1 gene, which encodes for the GCase enzyme, are the cause of Gaucher disease. Over the last decade, GBA1 mutations have also been identified as the most common genetic risk factor for Parkinson's. Individuals with Gaucher disease have an estimated 20-fold increased risk of developing Parkinson's disease, and an estimated 5% to 10% of those diagnosed with Parkinson's are carriers of Gaucher disease.
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