Glycoproteinoses


 * are proteins that have oligosaccharides covalently attached to the central chain
 * the weight share of carbohydrates in the molecule is 1% to 85%
 * unlike glycosaminoglycans, the carbohydrate units do not alternate regularly
 * they are mostly neutral in nature
 * very common carbohydrates are fucose and sialic acid
 * they 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 the extracellular matrix
 * the protein carrier is synthesized on the rough ER, carbohydrates are attached to it in GA in two way s:


 * 1) by an O-glycosidic bond to the OH group of Serine or Threonine of the protein using N-acetylglucosamine of the carbohydrate chain
 * 2) N-glycosidic bond to the NH 2 group of Asparagine protein using N-acetylglucosamine, to which the carbohydrate chain was transferred from the dolichol pyrophosphate carrier


 * degradation in lysosomes by endoglycosidases (fucosidase, aspartylglucosaminidase) and exoglycosidases (galactosidase, neuraminidase, hexosaminidase, mannosidase)

Glycoproteinoses

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

Mucolipidosis I (Sialidosis)

 * Defect: deficiency of  alpha-N-acetyl-neuraminidase activity  ( sialidase deficiency )
 * Clinical manifestations: depending on the onset and severity of symptoms, there are several clinical types - severe infantile form and lighter late infantile and adult forms
 * basic features in severe forms include "hurleroid" type dysmorphia, dysostosis multiplex, mental retardation, cherry spot on the fundus, and corneal opacities; there may also be hepatosplenomegaly, or kidney disease (nephrosialidosis)
 * accompanying manifestations  of the adult form are myoclonus induced by emotion and movement, a red spot on the fundus of the eye, and 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 is not available
 * Diagnosis: ML I is confirmed by determination of αN-acetyl-neuraminidase activity deficiency in cultured skin fibroblasts
 * Prenatal diagnosis:  in families with enzymatically proven diagnosis, analysis of native and cultured chorionic villi or cultured amniocytes is possible; an additional examination is an analysis of the ultrastructure of the chorionic villi

Mucolipidosis II (Inclusion disease, I-cell disease)

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


 * Clinical manifestations: clinically, a distinction is made between type II with faster progression and type III, which is a milder form
 * basic features 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 those affected may live into adulthood
 * basic features of type II include:
 * hurleroid appearance, coarse facial features bony deformity and mild joint stiffness
 * the disease starts early and progresses quickly, valvular defects are common - the most common cause of death is heart failure (before the age of 4)
 * lysosomes lack hydrolases, material accumulates in them, giving rise to inclusion bodies


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

Mannosidosa

 * Defect: acid α-mannosidase efficiency
 * Clinical manifestations: pronounced facial dysmorphia, psychomotor retardation, hepatosplenomegaly, corneal opacities, lens opacities, skeletal dysplasia, hearing impairment
 * there is a spectrum of clinical symptoms, but it is usual to divide it into a childhood form of α-mannosidosis ( infantile, type I ) and a form with later onset of clinical symptoms ( juvenile-adult, type II )
 * mannose-rich oligosaccharides accumulate in the tissues, which are increasingly excreted in the urine in a characteristic spectrum
 * Treatment: therapy is 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 enzymatically proven diagnosis, analysis of native and cultured chorionic villi or cultured amniocytes is possible; an additional examination is an analysis of the ultrastructure of the chorionic villi

Fucosidosis

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


 * Treatment: therapy is 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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Mucopolysaccharidoses