Lysosomal enzymes degrade macromolecules, either the macromolecules of the cell itself (for. Example, when the cell components are re-used) or outside the cell. The inherited defects or deficiencies of lysosomal enzymes can lead to an accumulation of undigested products. There are many specific defects that storage disorders are classified by biochemical point of view due to the accumulated metabolites. Sub-groups include Mukopolysaccharidosen Sphingolipidoses (lipidoses) Mucolipidosen See also approach in a patient with suspected congenital metabolic disorder The main groups are the mucopolysaccharidoses and Sphingolipidoses. Unlike most glycogen storage is in the type 2 glycogen storage disease is a lysosomal storage disease. Since the reticuloendothelial cells (z. B. spleen) rich in lysosomes, reticuloendothelial tissues are involved in a number of lysosomal storage diseases. In general, the substrate most tissues are most affected. Since the brain is rich in gangliosides, it is particularly affected by the Gangliosidoses while Mukopolysaccharidosen affect multiple tissue as mucopolysaccharides almost everywhere present in the body. Mucopolysaccharidosis (MPS) The mucopolysaccharidosis (MPS) is a congenital deficiency of enzymes involved in the degradation of glycosaminoglycans. Glycosaminoglycans (formerly known as mucopolysaccharides) are polysaccharides which are abundantly present on the cell surface, in the extracellular matrix, and their structures. Enzyme deficiencies, which prevent degradation of the glycosaminoglycan, causing an accumulation of fragments of the glycosaminoglycan in the lysosomes and thus pronounced bone, Weichteilgewebe- and CNS changes. Inheritance is usually autosomal recessive (with the exception of MPS type II). The presentation age and the clinical manifestations vary with the type (see table). The most common manifestations are coarse facial features, neurodevelopmental delays and regression, joint contractures, organomegaly, stiff hair, progressive respiratory failure (obstruction and sleep apnea), cardiovascular diseases, skeletal changes and dislocation of the cervical vertebrae. The diagnosis of mucopolysaccharidosis is due to history, clinical examination, bone abnormalities (eg. As dysostosis multiplex) that are found in bone overview, as well as increased total and fractionated urine glycosaminoglycans suspected diagnosis is by enzyme analysis of cultured fibroblasts (prenatal) or white blood cells (postnatal) confirmed. (See also check on suspicion of inherited metabolic disorders.) In order to monitor organ-specific changes are additional studies necessary (eg. As echocardiogram with heart valve diseases, audiometry at Hörveränderungen). The treatment of the MPS type I (Hurler syndrome) is an enzyme replacement with ?- l -Iduronidase which effectively prevents the progression and makes all CNS complications of the disease reversed. The hematopoietic stem cell (HSC) was also applied. A combination of enzyme replacement and HSC transplantation is examined immediately. In patients with MPS type IV-A (Morquio A syndrome), can improve an enzyme replacement with Elosulfase alfa functional status, including mobility. Mucopolysaccharidosis (MPS) disease (OMIM number) defects proteins or enzymes defective gene or genes (chromosomal location) Remarks MPS IH (Hurler’s syndrome; 607014) MPS IS (Scheie syndrome; 607,016) MPS IH / S (Hurler-Scheie syndrome; 607,015) ?-L-iduronidase IDUA (4p16.3) * start: in IH, 1st year For IS,> 5 years For IH / S, 3-8 years metabolites in urine: dermatan, heparan Clinical features: corneal opacity , stiff joints, contractures, dysostosis multiplex, coarse facial features, unruly hair, macroglossia, organomegaly, mental retardation mi t regression, valvular heart disease, hearing and vision problems, and inguinal hernia, sleep apnea, hydrocephalus treatment: Supportive care, enzyme supplementation, stem cell or bone marrow transplantation MPS II (Hunter syndrome; 309900) iduronate IDS (Xq28) * Start: 2-4 years metabolites in urine: dermatan, heparan Clinical features: Similar to Hurler’s syndrome, but lighter and with no corneal clouding normal With light course intelligence In severe cases progressive mental and physical disability, death before the age of 15 years treatment: Supportive care, stem cell or bone marrow transplantation MPS III (Sanfilippo syndrome) start: 2-6 years metabolites in urine: heparin sulfate Clinical features: Similar to Hurler’s syndrome, but with severe mental disabilities and mild somatic symptoms treatment : Supportive care Type III-A (252900) heparan sulfate-S-sulfamidase SGSH (17q25.3) * Type III-B (252920) of N-acetyl-D-glucosaminidase Naglu (17q21) * Type III-C (252930) acetyl-CoA -Glucosaminid N-acetyltransferase (14) type III-D (252940) of N-acetyl-Glucosaminin-6-sulfate sulfatase GNS (12q14) * M PS IV (Morquio Syndrome Start: 1-4 years metabolites in urine: keratin; with IV-B, chondroitin-6-sulfate Clinical features: Similar Hurler syndrome, but with severe bone changes including odontoider hypoplasia; may normal intelligence treatment: Supportive care for type IV-A enzyme replacement therapy with Elosulfase alfa type IV A (253000) Galactosamine-6-sulfate sulfatase GALNS (16q24.3) * Type IV-B (253010) ?-galactosidase GLB1 ( 3p21,33 * – s and GM1 gangliosidosis in Table sphingolipidosis) MPS VI (Maroteaux-Lamy syndrome; 253200) ?-N-acetylgalactosamine 4-sulfatase (arylsulfatase B) ARSB (5q11-q13) * start: Variable. but may be similar to Hurler’s syndrome Metabolites in urine: dermatan Clinical features: Similar to Hurler’s syndrome, but normal intelligence Treatment: Supportive care MPS VII (Sly syndrome; 253220) ?-glucuronidase GUSB (7q21,11) * Start: 1-4 years metabolites in the urine: dermatan sulfate, heparin, chondroitin 4-, 6-sulfate Clinical features: Similar Hurler syndrome, but larger differences in the severity of treatment: Supportive care, stem cell or bone marrow transplantation MPS IX (Hyaluronidasemangel; 601492) Hyaluronidasemangel HYAL1 (3p21.3-p21.2) * start: 6 months urinary metabolites: No Clinical features: Bilateral mass of periartikulärenn soft tissue, facial dysmorphism, short stature, normal intelligence treatment: Not set * The gene was identified, and the molecular basis has been elucidated. OMIM = Online Mendelian Inheritance in Man (see OMIM database). Sphingolipidoses sphingolipids are normal lipid components of the cell membrane that accumulate in lysosomes and cause distinct neural, bone and other changes if enzyme deficiencies prevent their degradation. Although the incidence is low, the carrier rate is very high in some forms. There are many types of sphingolipidosis (see TabelleDie common sphingolipidosis is angiokeratoma in Fabry disease © Springer Science + Business Media var model = {thumbnailUrl: ‘/-/media/manual/professional/images/401_angiokeratomas_slide_16_springer_high_de.jpg?la=de&thn=0&mw = 350 ‘, imageUrl:’ /-/media/manual/professional/images/401_angiokeratomas_slide_16_springer_high_de.jpg?la=de&thn=0 ‘, title:’ angiokeratoma in Fabry’s disease ‘, description:’ u003Ca id = “v38397321 “class = ” anchor “” u003e u003c / a u003e u003cdiv class = “” para “” u003e u003cp u003eDiese figure shows painless


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