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Lysosomal diseases ("storage diseases") are rare, inherited diseases leading to storage in lysosomes due to insufficient activity of any of the lysosomal enzymes, or transport proteins. These are multisystem diseases with persistent progression that can manifest at any time during life. Metabolically active organs and tissues (bone marrow, bones, skeletal muscles, myocardium and CNS) are mainly affected. About 60 different lysosomal disorders have been described. Early forms tend to be difficult with rapid progression and infamous prognosis. The incidence in our population is estimated at 1: 8200 live births. These are mostly autosomal recessive inherited diseases, rarely gonosomal recessive (Fabry disease and mucopolysaccharidosis type II). Lysosomal enzymes, so-called acid hydrolases, allow the gradual cleavage of large complex molecules (sphingolipids, glycoproteins or mucopolysaccharides)from the cell walls of vanishing cells. Insufficient amount or insufficient enzymatic activity leads to accumulation of substrate in lysosomes of different cells. Some diseases can be treated by substitution administration of recombinant enzymes (Gaucher, Fabry and Pompe disease, mucopolysaccharidosis type I, II AND VI) or by reducing the amount of stored substrate ("substrate reduction therapy" – Gaucher disease, Niemann-Pick disease type C). Bone marrow transplantation is rarely indicated (mucopolysaccharidosis type I).

Distribution

 * Lysosomal diseases from disorders of protein transport to lysosomes
 * Lysosomal diseases from lysosomal membrane protein deficiency
 * Lysosomal diseases due to lysosomal hydrolase deficiency
 * Lysosomal diseases due to deficiency of enzyme activators of lysosomal hydrolases

Pathophysiological mechanisms of lysosomal diseases and their examples

 * Storage of secondary products
 * Cholesterol (NPC C)
 * Sphingomyelin (NPC A, NPC B)
 * Mucopolysaccharides
 * neuroinflammation
 * Activation due to microglia, which act as phagocytes in the CNS, accumulate material in lysosomes, leading to their swelling (like foam cells in the atheroma plaque) and subsequently release lytic enzymes after their "rupture" (lysis)
 * Disorders of calcium metabolism
 * For example, Gaucher's disease, Gaucher's disease, a disorder of the enzyme glucosylcerebrosidase, which modulates the function of rhyadonide receptors in the sarcoplasmic (or endoplasmic) reticulum, which provide for the balance of calcium within the cell. When the receptors are damaged, calcium efflux from the endoplasmic reticulum occurs and thus activation of, among others, lytic enzymes, and caspases (apoptosis)
 * Oxygen radicals
 * It is probably related to endoplasmic reticulum and mitochondrial disorders, especially in the brain
 * Increased autophagy
 * Increased autophagy ultimately leads to apoptosis due to many factors. One of them is the need for poor circulation of the components of the plasma membrane, which leads to damage to the cell and its chemical and electrical gradients, and this leads to apoptosis

Cell disease (mucolipidosis type II)

 * GlcNAc-phosphotransferase deficiency.
 * Man-6-P is a chemical marker by which enzymes are addressed to lysosomes.
 * Inclusion cell disease is caused by a disorder in the transport of proteins containing the Man-6-P signal into lysosomes, which is caused by mutations in  N-acetylglucosamine 1-phosphotransferase.
 * The receptor for Man-6-P is unaffected, enzyme-bound Man-6-P is not formed.
 * This leads to increased activity of lysosomal proteins in extracellular fluid and plasma, and decreased activity of many lysosomal enzymes in tissues.
 * Lysosomes are enlarged due to lysosomal storage.
 * vacuolization of lymphocytes ("inclusion cells") storing lysosomes.
 * Patients have: rough facial features, thickened gums, small hepatomegaly and splenomegaly, bone disease– dysostosis multiplex, psychomotor retardation, increased plasma lysosomal hydrolase activities, low tissue activities.

Danon's disease

 * LAMP2 deficiency (Lysosomal-associated membrane protein 2)

Cystinosis

 * Cystinosin deficiency
 * Clinical manifestations:
 * Renal disease with Fanconi syndrome
 * Renal failure, kidney transplantation required
 * Corneal crystals, photophobia
 * Growth disorder
 * Normal intelligence
 * More on the page of sulfur metabolism disorders AMK

Sialuria

 * Sialin deficiency

Lysosomal diseases due to lysosomal hydrolase deficiency

 * Lysosomes contain different hydrolases depending on which stored substrate cleaves. Disorders of these enzymes lead to substrate accumulation in the lysosomal apparatus of the cell. Is part of them:
 * Lipidosis and Sphingolipidosis
 * Mucopolysaccharides
 * Mucopolysaccharides and Glycoproteinosis
 * Glycogenosis (this includes only glycogenase II-disease pump)
 * Proteinosis

Lipidosis
Lipidosis