Glycoproteinosis

Glycoproteins

 * are proteins that have oligosaccharides covalently attached to the oligosaccharide
 * weight fraction of carbohydrates in the molecule is 1% to 85%
 * Carbohydrate units, unlike glycosaminoglycans, do not change regularly
 * are mostly neutral
 * very common carbohydrates are fucose and sialic acid
 * have different functions - for example as antigens, enzymes
 * they are a standard part of membranes, they have catalytic functions, they are carriers of immunological specificity, they are part of mucus and also extracellular matrix
 * protein carrier is synthesized on the rough ER, in the GA carbohydrates are bound to it in two ways:
 * 1) O-glycoside bond to the OH group of Serine or Threonine protein using the N-acetylglucosamine carbohydrate chain
 * 2) N-glycoside bond to the NH 2 group of Asparagine protein using N-acetylglucosamine to which the carbohydrate chain has been transferred from a dolicholpyrophosphate support
 * degradation in lysosomes by endoglycosidases (fucosidase, aspartyl glucosaminidase) and exoglycosidases (galactosidase, neuraminidase, hexosaminidase, mannosidase)

Glycoproteinosis

 * usually  AR inheritance
 *  symptoms are similar to mucopolysaccharidosis, but there is no mucopolysaccharide accumulation or mucopolysacchariduria 
 * fragments of glycoproteins are present in the urine
 * lysosomal distension and secondarily induced increased activity of lysosomal enzymes occur

Mucolipidosis I (Sialidosis)

 * 'Defect:  'alpha-N-acetyl-neuraminidase' '' activity deficit
 * Clinical manifestations: depending on the onset and severity of symptoms, there are several clinical types - severe infantile form and ' mild late infantile and adult forms
 * The basic features of severe forms include dysurphias of the "hurleroid" type, multiplex dysostosis, mental retardation, a cherry spot on the back of the eye, and corneal opacity; it can also be hepatosplenomegaly, event. kidney disease (nephrosialidosis)
 * Accompanying manifestations of adult form include myoclonus induced by emotion and movement, a red spot on the back of the eye, and an intact intellect; there may be other neurological symptoms including mild sensorimotor peripheral neuropathy
 * there is an increased amount of sialyloligosaccharides in the urine, which may not be detectable in milder forms of the disease with late onset
 * Treatment: therapy not available
 * Diagnosis: ML I is confirmed by determining the deficiency of α-N-acetyl-neuraminidase activity in cultured skin fibroblasts
 * Prenatal diagnosis: in families with an enzymatically proven diagnosis is possible by analysis of native and cultured chorionic villi or cultured amniocytes; an additional examination is the analysis of the ultrastructure of chorionic villi

Mucolipidosis II (Inclusion disease, I-cell disease)

 * Defect: mutation of lysosomal enzyme N-acetylglucosaminyl-1-phosphotransferase leading to secondary multiple deficiency of lysosomal enzymes due to their erroneous transport (defect in the gene encoding the enzyme protein)
 * Decreased activity of many lysosomal enzymes in tissues
 * increase in lysosomal protein activity in extracellular fluid (and plasma)


 * Clinical manifestations: clinically distinguishes type II with faster progression and 'type III, which is milder form
 * the basic characters of type III include:
 * late infantile form, bone changes predominate, other characteristics are dwarfism, dysmorphia, joint involvement and stiffness
 * brain functions tend to be mildly affected
 * Progression is slow and people with disabilities can live to adulthood
 * basic characters of type II include:
 * hurleroid appearance, rough facial features of bone deformity and mild stiffness of the joints
 * the disease develops early and progresses quickly, valve defects are common - the most common cause of death is heart failure (before the age of 4)
 * hydrolases are missing in lysosomes, material accumulates in them, which gives rise to inclusion bodies


 * Treatment: therapy not available
 * Diagnosis: mucolipidosis II and III is confirmed by determining the deficiency of phosphotransferase activity in leukocytes isolated from peripheral blood or cultured skin fibroblasts, or indirectly by determining a multiple increase in serum lysosomal hydrolase activities and simultaneously determining the deficiency of these hydrolases in cultured skin fibroblasts. fibroblasts
 * Prenatal diagnosis: in families with enzymatically proven diagnosis is possible by analysis of amniotic fluid supernatant and cultured amniocytes or cultured chorionic villi

Mannosidosa

 * Defect: acidic α-mannosidase effect
 * Clinical manifestations: severe facial dysmorphia, psychomotor retardation, hepatosplenomegaly, corneal opacity, lens opacities, skeletal dysplasia, hearing impairment
 * there is a spectrum of clinical symptoms, but it is common to divide into a pediatric form of α-mannosidosis( infantile, type I ) and a form with later onset of clinical symptoms (juvenile - adult, type II)
 * oligosaccharides rich in mannose accumulate in the tissues, which are increasingly excreted in the urine in the characteristic spectrum
 * Treatment: therapy not available
 * Diagnosis: is confirmed by determining the deficiency of α-mannosidase activity in leukocytes isolated from peripheral blood or cultured skin fibroblasts
 * Prenatal diagnosis: in families with an enzymatically proven diagnosis is possible by analysis of native and cultured chorionic villi or cultured amniocytes; an additional examination is the analysis of the ultrastructure of chorionic villi

Fucosidosis

 * Defect: α-L-fucosidase deficit
 * Clinical manifestations: basic features include neurological symptoms starting after the first year of life, hypotension, psychomotor retardation, later spasticity, seizures and decerebral rigidity
 * There may be mild dysmorphia, skeletal abnormalities and other signs of mesenchymal involvement
 * in milder forms with late onset of clinical symptoms are angiokeratomas
 * traditionally there are two clinical phenotypes, severe infantile type I and milder type II
 * low molecular weight fucoconjugates accumulate in the tissues, possibly. and fucoglycolipids, there is oligosacchariduria in the urine with a characteristic spectrum


 * Treatment: therapy not available
 * Diagnosis: fucosidosis is confirmed by determining the deficiency of α-fucosidase activity in leukocytes isolated from peripheral blood or cultured skin fibroblasts

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