Glycoproteinoses

For more information see Glycoproteins.

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 ways:

by an O-glycosidic bond to the OH group of Serine or Threonine of the protein using N-acetylglucosamine of the carbohydrate chain
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[edit | edit source]

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

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

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

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

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

MURRAY, Robert K. – GRANNER, Daryl K. – MAYES, Peter A., et al. Harperova BIOCHEMIE. 4. edition. Jinočany. 2002. ISBN 80-7319-013-3.

HYÁNEK, Josef, et al. Dědičné metabolické poruchy. 1. edition. Praha : Avicenum, 1990. pp. 342. ISBN 80-201-0064-4.