CDG Glossary of Terms
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X-linked recessive
A mode of inheritance where a recessive allele is located on the X chromosome. Males are much more likely to demonstrate these traits as they only possess a single X chromosome, which allows the recessive gene to determine the phenotype.
X-linked
A mode of inheritance that is caused when the gene of interest is located on the X chromosome.
w
Whole genome sequencing (WGS)
Sequencing of an organism’s entire genetic code (genome).
Whole exome sequencing (WES)
Sequencing of all expressed genes.
v
Vesicle
An enclosed structure that transports proteins and other molecules around the cell or to the cell surface.
Vesicular trafficking
A transport system wherein vesicles are used to move substances around or to the surface of the cell.
t
Type II pattern
An aberrant pattern of transferrin glycosylation typical of defects in N-linked protein glycosylation that occur after the attachment of the oligosaccharide precursor to the protein; characterized by elevated levels of trisialo- (three sialic acids), disialo-, monosialo- and/or asialotransferrin.
Type I pattern
An aberrant pattern of transferrin glycosylation typical of defects in N-linked protein glycosylation that occur in the ER prior to the attachment of the oligosaccharide precursor to the protein; characterized by low overall levels of glycosylation with elevated levels of asialo- (no sialic acids) or monosialotransferrin (one sialic acid) isoforms, instead of the normal tetrasialotransferrin.
Type II CDG
An N-linked CDG caused by defects in the processing of the N-glycans attached to proteins. Traditionally, CDG were classified as either Type I or Type II CDG, but this classification system can only differentiate CDG caused by defects in N-glycosylation and is no longer used to classify CDG types. Also called CDG-II.
Type I CDG
An N-linked CDG caused by defects in the assembly and transfer of oligosaccharide to an asparagine residue on a protein. Traditionally, CDG were classified as either Type I or Type II CDG, but this classification system can only differentiate CDG caused by defects in N-glycosylation and is no longer used to classify CDG types. Also called CDG-I.
Transferrin
An iron-binding plasma protein that is used a diagnostic biomarker for N-linked CDG. Normally, transferrin has two N-glycans each with two sialic acid sugars (tetrasialotransferrin). Reduced or altered transferrin glycosylation is a common sign of N-linked congenital disorders of glycosylation.
Transferrin isoform analysis
Any number of techniques used to determine the presence of different isoforms of serum transferrin in a blood sample; also called carbohydrate deficient transferrin (CDT) analysis. The most common technique is transferrin isoelectric focusing, but mass spectrometry is increasingly used to analyze different glycosylation patterns on transferrin in greater detail. Carbohydrate deficient transferrin is commonly found in N-linked congenital disorders of glycosylation.
Transferrin isoelectric focusing (TIEF)
A method used to separate transferrin isoforms with different levels of glycosylation using gel electrophoresis; a common method of carbohydrate deficient transferrin analysis that is used in the diagnosis of suspected CDG.
Transaminases
Enzymes that transfer an amino group from an amino acid to an acceptor molecule, typically an alpha-ketoacid. In the process, a new amino acid is prepared. Transaminases play an important role in amino acid metabolism and synthesis. Also called aminotransferases.
Thrombocytopenia
Abnormally low levels of platelets in the blood.
s
Strabismus
A glycosyltransferase that facilitates the transfer of a sialic acid sugar from a sialic acid-based activated sugar to another molecule.
Sphingolipid
A molecule comprised of a lipid attached to sphingosine.
Solute carrier proteins
A large group of proteins that move substances across a membrane, e.g. as part of nutrient uptake or waste disposal.
Sialyltransferase
A glycosyltransferase that facilitates the transfer of a sialic acid sugar from a sialic acid-based activated sugar to another molecule.
r
Retinitis pigmentosa
An eye disorder that causes progressive vision loss.
Residue
A subunit of a larger biomolecule, e.g. a single amino acid in a protein or a specific sugar in an oligosaccharide.
Remodelling
A general term for the process by which a biomolecule is modified by the addition, removal, or exchange of certain subunits. In the context of glycosylation, remodeling may involve modifications of the glycan component of glycoproteins and glycolipids (glycan remodelling). The lipid component of glycolipids may also be altered (lipid remodelling).
Radiolabeled
A molecule that has a non-radioactive atom substituted with a radioactive atom, making it easier to detect using certain analytical techniques.
p
Proteoglycans
A type of O-linked glycoprotein characterized by the attachment of glycosaminoglycan polysaccharide chains.
Protein-losing enteropathy
A condition where an excess loss of proteins occurs through the gastrointestinal tract; PLE.
Protein glycosylation
A common post-translational modification of proteins in which a sugar or sugar chain is attached to specific amino acids in the protein.
Proteases
Enzymes that break down other proteins.
Post-GPI attachment to protein (PGAP) enzymes
Proteins in the ER and the Golgi that are involved in the remodeling of the lipid and glycan components of GPI-anchored proteins after the protein has been attached to the GPI anchor.
Polysaccharide
A long sugar chain (more than 20 monosaccharides combined together); also called a glycan.
Phosphatidylinositol glycan anchor biosynthesis (PIG) enzymes
A class of enzymes involved in the synthesis of the glycan portion of the GPI anchor.
Phosphatidylinositol (PI)
A membrane-bound glycerophospholipid with a glycerol backbone connected to two fatty acid lipid tails and an inositol sugar.
Phenotype
The observable effects of a specific gene; e.g. clinical presentation of a person with a specific CDG.
Pharmacological chaperones
A drug or small molecule that helps misfolded proteins to fold and function correctly within the cell.
o
Oligosaccharide precursor
The 14-sugar (Glc3Man9GlcNAc2)oligosaccharide that is built on dolichol pyrophosphate (dol-PP) in the ER prior to its transfer to an asparagine residue of a protein as part of N-glycosylation; glycan component the lipid-linked oligosaccharide (LLO). Also called the N-glycan precursor oligosaccharide.
Oligosaccharide
A short sugar chain (less than 20 monosaccharides combined together); also called a glycan.
O-glycosylation
The process wherein a sugar is transferred from an activated sugar to an oxygen atom (O) of a serine, threonine, tyrosine or hydroxylysine amino acid on a protein. Different types of O-glycosylation may occur in the ER, nucleus, Golgi, cytoplasm, or mitochondria.
O-glycan
A glycan chain that is attached to an O-glycoprotein, usually at a serine or threonine residue.
n
Nystagmus
Abnormal eye movements.
Nucleotide sugars
A sugar that has been activated for attachment to another molecule by first forming a reactive bond with a nucleotide diphosphate; a type of activated sugar.
Nucleotide sugar transporter
A protein that transports nucleotide sugars (a type of activated sugar) into the Golgi and Endoplasmic Reticulum lumen.
Nucleosides
A structural subunit of nucleic acids such as RNA or DNA.
N-glycosylation
The process wherein the glycan chain Glc3Man9GlcNAc2 is transferred from the lipid-linked oligosaccharide to a nitrogen atom (N) of an asparagine residue in a newly synthesized protein in the ER; the asparagine must be part of Asn-X-Ser/Thr consensus sequence for the glycosylation to occur. After attachment, the N-glycan chain undergoes further modifications in the ER and the Golgi to yield a mature N-glycoprotein.
N-glycan
A glycan chain that is attached to an N-glycoprotein at an asparagine residue.
Nephrocalcinosis
A disorder that occurs when too much calcium is deposited in kidney tissue.
m
Myopathy
A disease that affects muscle tissue. Common symptoms are muscle weakness, inflammation, pain, spasms, or paralysis.
Monosaccharide
A single sugar molecule; monosaccharides are combined as the building blocks of larger sugar chains (i.e. glycans and oligosaccharides).
Mixed type I/II pattern
An aberrant pattern of transferrin glycosylation which displays aspects of both Type I and Type II patterns and may be caused by glycosylation defects in both the ER and the Golgi.
Micrognathia
An undersized lower jaw.
Microcephaly
An underdeveloped head that is much smaller than expected.
Mass spectrometry
A method that determines exact mass of a molecule, which can be extrapolated to help identify its chemical makeup.
Mannosyltransferase
A glycosyltransferase that facilitates the transfer of a mannose group from a mannose-based activated sugar to another molecule.
Mannosidase
A glycosidase that removes mannose sugars from the ends of sugar chains.
l
Lipid remodelling
The removal, addition, modification, or exchange of lipids in newly synthesized glycolipids; part of the process by which glycolipids are converted to their fully functional, mature forms.
Lipid rafts
Within the plasma membrane, a spontaneous and dynamic self-association and enrichment of certain lipids, proteins and membrane associated molecules.
Lipid-linked oligosaccharide (LLO)
A poly- or oligosaccharide attached to dolichol and anchored in the ER membrane. In the context of N-glycosylation, the LLO is built by the sequential attachment of sugars to dolichol pyrophosphate (Dol-PP) to form a 14-sugar (Glc3Man9GlcNAc2) oligosaccharide; this oligosaccharide is transferred to proteins during N-glycosylation.
Lipid glycosylation
The attachment of a sugar group to a lipid.
k
Kinases
Enzymes that add phosphate groups to molecules.
i
Isoform
Different forms of the same protein. For example, if two proteins have the same amino acid sequence but have different glycan chains, they are isoforms.
h
Hypsarrhythmia
Disorganized and chaotic brain electrical activity that is the most common electroencephalogram (EEG) pattern associated with infantile spasms.
Hypotonia
Low muscle tone, often with reduced muscle strength.
Hypothyroidism
Decreased production of thyroid hormones.
Hypolipidemia
Low levels of lipids (such as cholesterol or lipoprotein) in the blood.
Hypoglycosylation
Absent, improper, or inadequate addition of sugar groups to other molecules such as proteins or lipids.
Hypoglycemia
Low blood glucose levels.
Hypoalbuminemia
Low concentration of albumin protein in the blood.
Hyperphosphatasia
Increased levels of the enzyme alkaline phosphatase in the blood.
Hyperreflexia
Overactive or overresponsive reflexes.
Hydrops fetalis
Life threatening accumulation of fluid in two or more body compartments of an unborn or newborn baby.
High-performance liquid chromatography (HPLC)
An analytical technique that separates molecules based on their chemical properties and can allow analysis of complex mixtures.
g
Granulocyte
A type of white blood cell that is part of the immune system and is characterized by possessing numerous granules in the cytoplasm. These granules store many cytotoxic and antimicrobial molecules that are released following certain immune stimuli.
GPI-anchored proteins
Proteins that are attached to GPI and anchored to the outer surface of the cell membrane.
Golgi Apparatus (Golgi)
The compartment of a cell where proteins are further processed and packaged for their destination in/on the cell. Glycan chains on glycoproteins are often modified by enzymes in the Golgi as part of their normal maturation.
Glycosyltransferase
Enzymes that facilitate the transfer of sugar groups from glycosyl donors to glycosyl acceptors (e.g. proteins, lipids or other sugars) during glycosylation.
Glycosylphosphatidylinositol (GPI)
A type of glycolipid present in the cell membrane that acts as an attachment point for membrane-bound proteins, effectively anchoring them to the cell surface.
Glycosylphosphatidylinositol (GPI) anchor biosynthesis
Synthesis and attachment of a GPI molecule to the base of a protein.
Glycosylation
An enzymatic process that attaches sugars to proteins, lipids, or other sugars. This process requires adequate formation of glycosyl donors, functional glycosyltransferases, and can be proceeded by further modification of the resultant sugar group.
Glycosyl donors
Any high-energy forms of mono or oligosaccharides that allow the sugar group to be transferred or “donated” onto other molecules; also called sugar donors or activated sugars.
Glycosyl acceptors
Any molecule to which a sugar group is added. Common glycosyl acceptors in the body are proteins, lipids, or other sugar chains.
Glycosphingolipids (GSLs)
A type of glycolipid with ceramide as the core lipid structure.
Glycosidic bond
A bond formed between a monosaccharide and another molecule.
Glycosidase
An enzyme that removes a sugar from an oligo- or polysaccharide.
Glycoprotein
Proteins with one or more glycan (sugar chain) attached.
Glycolysis
The process by which glucose is broken down to generate energy for cells.
Glycolipid
A molecule containing a glycan (sugar chain) attached to a lipid.
Glycogenesis
The process of connecting many glucose sugars together to form glycogen.
Glycogen
A large chain of glucose sugars that is used to store energy in the body, particularly in the liver and in muscle cells.
Glycoform
A variation of a protein, where different glycan chains cause differences in protein function and/or structure.
Glycerophospholipid
A type of lipid that has a glycerol backbone; the glycerol is substituted with fatty acids and a hydrophilic phosphorus group (phosphate).
Glycan remodeling
The removal, addition, modification, or exchange of sugars in the glycan chains of newly synthesized glycoproteins and glycolipids; part of the process by which glycoproteins and glycolipids are converted to their fully functional, mature forms.
Glycan
A large sugar molecule made up of multiple sugars (monosaccharides), also known as an oligosaccharide. It may exist attached to another molecule, such as a protein or lipid, or in free form.
Glucosyltransferase
A glycosyltransferase that facilitates the transfer of glucose from a glucose-based activated sugar to another molecule.
Globoside
A type of glycosphingolipid that has more than one sugar as the side chain of its ceramide moiety; globosides are predominantly found on the surface of red blood cells.
Gene therapy
An experimental way of treating or preventing disease by modifying the genetic material of a patient. This may include replacing a defective gene with a normal gene, adding a new or modified gene, or deactivating a gene that could cause disease.
Gene sequencing
A method that determines the DNA sequence of a particular gene.
Ganglioside
A type of glycosphingolipid enriched in the brain and nervous tissue, characterized by a glycan chain possessing at least one sialic acid sugar.
f
Flow cytometry
A technique used to analyze the physical and chemical properties of cells.
Failure to thrive
Term used for children who have failed to gain weight or height according to medical standards.
e
Endoplasmic Reticulum (ER)
A membrane-bound compartment of the cell where proteins and lipids are synthesized.
Endoplasmic reticulum associated degradation (ERAD)
A quality control process where misfolded proteins in the ER are broken down by the proteosome. After a misfolded protein is recognized, it is transported out of the ER and modified by the additional of many ubiquitin groups (polyubiquitination) which causes it to be transported to the proteasome for degradation.
d
Dystroglycanopathies
Neuromuscular disorders caused by abnormal glycosylation of dystroglycan, a cell-surface O-glycoprotein.
Dysmorphism
An abnormal difference in body structure.
Dolichol-P-mannose
An activated sugar that serves as a mannose donor in the ER.
Dolichol-P-glucose
An activated sugar that serves as a glucose donor in the ER.
Dolichol
A lipid that is present in the ER membrane that can be combined with sugars to create activated sugars which are anchored to the ER. These dolichol-linked activated sugars enable the attachment of sugars to other biomolecules in the ER and play key roles in N-glycosylation, GPI-anchor biosynthesis, O-mannosylation and C-mannosylation.
Disorder of multiple glycosylation pathways
A subgroup of congenital disorders of glycosylation where multiple glycosylation pathways are affected.
Dietary supplementation
Any method used to treat or prevent disease by adding specific nutrients to the diet of the patient; also called nutritional therapy or nutritional supplementation. Dietary supplementation is a common component of dietary therapy.
Deglycosylation
The process of removing a sugar group from a molecule, such as a protein.
c
C-terminal GPI attachment sequence
An amino acid sequence that marks proteins to be attached to a GPI anchor by the GPI transamidase complex.
Core 1 mucin type O-glycan
A type of abundant O-glycan; an N-acetylgalactosamine attached to a serine or threonine residue of a protein, followed by a galactose residue (Gal-GalNac-Ser/Thr).
Consensus sequence
A series of amino acids that allow a protein to be targeted by another enzyme. E.g., the Asn-X-Ser/Thr consensus sequence allows newly formed proteins to be recognized by oligosaccharyltransferase (OST).
Congenital Disorder of Glycosylation (CDG)
An umbrella term that is used to categorize any disorder that results in the absent, improper or inadequate assembly of sugar groups to another molecule.
Congenital Disorder of Deglycosylation (CDDG)
Any genetic disorder caused by an inability to properly remove sugar groups from another molecule.
Coloboma
A hole or gap in one of the structures of the eye, such as the retina or iris.
Chaperones
Proteins that interact with newly synthesized polypeptides in the ER to make sure they are properly folded.
Ceramide
A type of sphingolipid, where a fatty acid is attached to the nitrogen of the lipid-like molecule sphingosine; a key lipid component of glycosphingolipids.
Cardiomyopathy
Disease of the heart muscles.
Carbohydrate deficient transferrin (CDT) analysis
Any number of techniques used to determine the presence of different isoforms of serum transferrin in a blood sample. The most common technique is transferrin isoelectric focusing, but mass spectrometry is increasingly used to analyze different glycosylation patterns on transferrin in greater detail. Carbohydrate deficient transferrin is commonly found in N-linked congenital disorders of glycosylation.
Carbohydrate deficient transferrin (CDT)
Transferrin isoforms that are lacking sialic acid residues; a common abnormal glycosylation pattern observed in serum transferrin isoform analysis of N-linked congenital disorders of glycosylation.
a
Autosomal recessive
The inheritance pattern observed when a single copy of a gene (allele) is insufficient to control the genetic outcome (phenotype) that corresponds to the gene, and the gene is located on an autosome (any chromosome that is not the X or Y sex chromosome); if a disease is inherited in an autosomal recessive fashion, both copies of the gene need to be abnormal for the disease to be present.
Autosomal dominant
The inheritance pattern observed when one copy of the gene (allele) controls the genetic outcome (phenotype) that corresponds to the gene, and the gene is located on an autosome (any chromosome that is not the X or Y sex chromosome); if a disease is inherited in an autosomal dominant fashion, only one copy of the gene needs to be abnormal for the disease to be present.
Ataxia
Impaired coordination and lack of muscle control; a common symptom of CDG.
Asn-X-Ser/Thr consensus sequence
A sequence of amino acids on a protein that is recognized by the oligosaccaryltransferase complex (OST) and is required for the transfer of the N-glycan precursor (Glc3Man9GlcNAc2) from the LLO to the asparagine residue as part of N-linked protein glycosylation. If an asparagine residue is not followed by an X (any amino acid except proline) and then serine or threonine, Glc3Man9GlcNAc2 will not be added to the protein by OST.
Apolipoprotein C-III isoform analysis
An O-linked glycoprotein encoded by the APOC3 gene and secreted by the liver and small intestines. It is often tested as a biomarker for disorders of O-linked glycosylation and CDG with Golgi defects.
Apolipoprotein C-III
An O-linked glycoprotein encoded by the APOC3 gene and secreted by the liver and small intestines. It is often tested as a biomarker for disorders of O-linked glycosylation and CDG with Golgi defects.
Alpha-dystroglycan
One of two subunits of dystroglycan, an adhesion protein that important for proper functioning of muscle cells. O-mannosylation of alpha-dystrogylcan is important for its function.
Allele
One of several alternative forms of a gene, responsible for alternative traits; humans have two alleles per gene, one inherited from each parent.
Acyltransferase
An enzyme that transfers a fatty acid onto another biomolecule.
Activated sugars
High-energy forms of mono or oligosaccharides that allow the sugar group to be transferred onto other molecules; also called sugar donors.
d
Disorder of monosaccharide synthesis
Any genetic disorder the prevents adequate construction of a given monosaccharide. Since monosaccharides are the building blocks of more complex glycan chains, a deficiency in a particular monosaccharide will negatively affect multiple glycosylation pathways.
Disorder of monosaccharide interconversion
Any genetic disorder the prevents the transformation of a monosaccharide into a different sugar. Monosaccharide interconversion is an important mechanism for maintaining adequate balances of different sugars in the body. Since monosaccharides are the building blocks of more complex glycan chains, impaired monosaccharide interconversion will negatively affect multiple glycosylation pathways.
Disorder of dolichol metabolism
Any genetic disorder the prevents adequate synthesis of the lipid dolichol. In N-glycosylation, the oligosaccharide is built upon dolichol before it is transferred to N-glycoproteins. Activated sugars Dol-P-mannose and Dol-P-glucose act as sugar donors for several types of glycosylation occurring in the ER. Thus, disorders of dolichol metabolism negatively affect glycosylation in the ER and impact multiple pathways.
Disorder of nucleotide sugar synthesis
Any genetic disorder that prevents the adequate construction of nucleotide sugars, a type of activated sugar, or prevents the nucleotide sugar from entering the compartments of the cell where it is needed for glycosylation. Since nucleotide sugars are a key class of activated sugars involved in the synthesis of glycolipids/glycoproteins, disorders of nucleotide sugar synthesis will negatively affect multiple glycosylation pathways.
Disorder of nucleotide sugar transport
Any genetic disorder that prevents nucleotide sugars, a type of activated sugar, nucleotide sugar from entering the compartments of the cell where it is needed for glycosylation. Since nucleotide sugars are a key class of activated sugars involved in the synthesis of glycolipids/glycoproteins, disorders of nucleotide sugar transport will negatively affect multiple glycosylation pathways.
Disorder of nucleotide sugar synthesis and transport
Any disorder that prevents the adequate construction of nucleotide sugars, a type of activated sugar, or prevents the nucleotide sugar from entering the compartments of the cell where it is needed for glycosylation. Since nucleotide sugars are a key class of activated sugars involved in the synthesis of glycoproteins/glycolipids, disorders of nucleotide sugar synthesis and transport will negatively affect multiple glycosylation pathways.
Disorder of vesicular trafficking
Any disorder that prevents the normal movement of various biomolecules between different compartments or to the surface of the cell using vesicles. Vesicular trafficking is particularly important for the movement of glycoconjugates and proteins involved in glycosylation from the ER to the Golgi, and disorders of vesicle trafficking may negatively impact multiple glycosylation pathways.
Disorder of Golgi homeostasis
A disorder that impacts normal glycosylation due to dysregulation of the Golgi. Since the Golgi is a major site of glycan remodelling in cells, any mutation that negatively impacts its normal function may have downstream impacts on the synthesis of glycoproteins/glycolipids in multiple glycosylation pathways.
Disorder of N-linked protein glycosylation
Any genetic disorder that primarily prevents the proper formation of mature N-linked glycoproteins.
Disorder of O-linked protein glycosylation
Any genetic disorder that primarily prevents the proper formation of mature O-linked glycoproteins.
Disorder of GPI-anchor biosynthesis
Any genetic disorder that primarily prevents the proper formation of glycosylphosphatidylinositol (GPI) anchors.
Disorder of lipid glycosylation
Any genetic disorder that primarily prevents the proper formation of glycosphingolipids (a subtype of lipids).
a
Alacrima
Inability to form tears and keep the eye moist.
b
Branching
When a glycan splits into two or more oligosaccharide chains attached to the same sugar residue, similar to limbs growing out from tree.
c
Cerebellum
The part of the brain that is responsible for coordinating voluntary movements and is also important for balance, coordination, and posture.
Cerebellar atrophy
Progressive degeneration of the cerebellum which cause the cerebellum to appear small but otherwise structurally normal; typically associated with difficulties in walking, coordinated movements, and speech.
Coagulopathy
A condition in which blood is not able to properly form clots, which can result in prolonged or excessive bleeding.
d
Deglycosylation
The removal of a sugar or oligosaccharide from another molecule.
Disorder of nucleotide sugar synthesis
Any genetic disorder that prevents the adequate construction of nucleotide sugars, a type of activated sugar, or prevents the nucleotide sugar from entering the compartments of the cell where it is needed for glycosylation. Since nucleotide sugars are a key class of activated sugars involved in the synthesis of glycolipids/glycoproteins, disorders of nucleotide sugar synthesis will negatively affect multiple glycosylation pathways.
Disorder of nucleotide sugar transport
Any genetic disorder that prevents nucleotide sugars, a type of activated sugar, nucleotide sugar from entering the compartments of the cell where it is needed for glycosylation. Since nucleotide sugars are a key class of activated sugars involved in the synthesis of glycolipids/glycoproteins, disorders of nucleotide sugar transport will negatively affect multiple glycosylation pathways.
Disorder of vesicle trafficking
Any disorder that prevents the normal movement of various biomolecules between different compartments or to the surface of the cell using vesicles. Vesicular trafficking is particularly important for the movement of glycoconjugates and proteins involved in glycosylation from the ER to the Golgi, and disorders of vesicle trafficking may negatively impact multiple glycosylation pathways.
Dysarthria
A neuromuscular condition that causes an inability to clearly speak due to weakness in the muscles that control speech; this weakness is neurological in origin.
Dystonia
A type of movement disorder in which muscles spasm or contract involuntarily or get stuck in abnormal positions.
g
Glycosaminoglycan (GAG)
A type of linear glycan chain that is composed of repeating two-sugar (disaccharide) units. Each disaccharide unit is made of an amino sugar and a uronic acid sugar. GAGs are capable of holding a holding a significant amount of water and are thus important for maintaining tissue hydration.
Galactosylation
The process of adding galactose from a galactose-based activated sugar to another molecule.
Galactosyltransferase
An enzyme that facilitates the transfer of galactose from a galactose-based activated sugar to another molecule.
Genotype
Broadly, the genetic makeup of an organism as defined by its complete set of genes. More narrowly, the combination of genes that contribute to a specific genetic trait in an organism.
Glycoconjugate
Any molecule that has a sugar attached to it, e.g. glycolipids or glycoproteins.
h
Hepatomegaly
An abnormally enlarged liver.
Hypocholesterolemia
Abnormally low levels of cholesterol in the blood.
Hypoplasia
A lack of cells that causes an organ or tissue to be small or incompletely developed.
i
Ichthyosis
A skin condition characterized by dry, scaly, thickened, cracked skin.
Isoelectric focusing (IEF)
A technique that can be used to separate proteins based on their electric charge. Often used to analyse the number of sialic acid residues present on the glycan chains of O- or N-linked glycoproteins.
k
Kyphosis
An excessive forward curvature of the back.
l
LLO analysis
Any technique used to analyse the structure of the lipid-linked oligosaccharide (LLO) in a patient, often involving the sampling of patient fibroblasts. Defects in the LLO are indicative of type I N-linked CDG.
m
Mosaicism
When an organism has two or more sets of cells each with a different genetic makeup (genotype), often as the result of a mutation or error in cell division where one of the daughter cells has a different genetic makeup from the mother cell. It can affect any type of cell.
Muscular dystrophy
Any disease that causes progressive weakening and breakdown of the muscles.
n
Nucleus
The membrane-bound compartment of a cell that contains the genetic information (chromosomes).
p
Peripheral neuropathy
Any condition that causes damage to the nerves outside of the brain and spinal cord, which comprise the central nervous system.
Phosphatase
A type of enzyme that catalyses the cleavage of phosphate from other biomolecules such as sugars or phospholipids.
Proteasome
A protein complex that breaks down unneeded, damaged, or misfolded proteins as part of ERAD.
r
Repurposed drugs
The reuse of an already FDA-approved drug to treat a condition that they are not currently approved for; using repurposed drugs is significantly faster than discovering and approving a new drug.
Retinal dystrophy
A progressive and severe loss of vision that results from changes to the shape or functioning of the light-sensitive part of the eye known as the retina, for example due to the loss of photoreceptors.
Retrograde trafficking
The movement of proteins in the opposite direction of the normal protein secretion pathway, e.g. the transport of proteins from Golgi to the endoplasmic reticulum. This “backwards” movement of proteins is important for maintaining a steady-state localization of proteins in the cell.
s
Sialylation
The process of adding sialic acid from a sialic acid-based activated sugar to another molecule.
Skeletal dysplasia
Any condition which causes the bones and cartilage of a child to develop abnormally, causing disproportion of the spine, head, and long bones such as those in the arms and legs; sometimes called dwarfism.
Scoliosis
An abnormal sideways curvature in the spine.
Synthase
An enzyme that catalyses a step in the building-up (synthesis) of a molecule.
t
Total glycan analysis
The process of determining the overall prevalence, structures, and defects of glycans in a patient sample. Often involves treatment of a blood sample so that glycans are cleaved from glycoproteins and can then be analysed, for example using mass spectrometry.
Total N-glycan analysis
The process of determining the prevalence, structure, and defects in any glycan attached to a protein via N-glycosylation. Often involves treatment of a blood sample so that N-glycans are cleaved from N-glycoproteins and can then be analysed, for example using mass spectrometry.
Total O-glycan analysis
The process of determining the prevalence, structure, and defects in any glycan attached to a protein via O-glycosylation. Often involves treatment of a blood sample so that O-glycans are cleaved from O-glycoproteins and can then be analysed, for example using mass spectrometry.
d
Dystroglycanopathies
A group of glycosylation-related disorders affecting O-mannosylation of the alpha-dystroglycan protein.