Carbohydrate-Deficient Glycoprotein Syndrome Type III

Carbohydrate-deficient glycoprotein syndrome type III is an old name for a group of very rare, inherited diseases where the body does not add sugar chains to proteins in the normal way. Today these conditions are usually called congenital disorders of glycosylation (CDG), and “type III” is used when tests clearly show a CDG pattern but doctors still do not know the exact gene or enzyme that is wrong.

Carbohydrate-deficient glycoprotein syndrome type III is an older name used for a very rare genetic condition now grouped under the congenital disorders of glycosylation (CDG), especially a form linked to changes in the COG5 gene that affects how the Golgi apparatus builds sugar chains (glycans) on proteins. [1] These sugar chains are important for brain development, muscles, liver, hormones, immunity, and many other systems, so people with this condition can have low muscle tone, delayed milestones, learning difficulties, poor coordination, and sometimes vision or hearing problems. [2] The condition is usually inherited in an autosomal recessive way, which means both parents quietly carry one changed copy of the gene. [3] There is no single cure; treatment mainly focuses on relieving symptoms and supporting development with a specialist team. [4]

Glycosylation is a process where small sugar chains are attached to proteins and fats. These sugar chains help proteins fold, move inside the cell, and work correctly in organs such as the brain, liver, muscles, gut, and blood vessels. When this process is faulty, many organs can be affected at the same time, so children may have problems with movement, learning, growth, feeding, liver function, blood clotting, and hormones.

In the MedGen system, carbohydrate-deficient glycoprotein syndrome type III is linked to the label “CDG-X” or “congenital disorder of glycosylation type I/IIx”. This means the child has clear biochemical signs of a CDG, but the exact subtype has not yet been matched to a known gene. The cases under this label probably include several different very rare CDG forms that are still being discovered.

These conditions are autosomal recessive. This means a child is affected when they receive one faulty copy of the gene from each parent. Parents who each carry one faulty copy usually have no symptoms themselves.

Other names

Doctors and researchers may use different names for the same group of patients:

• “Carbohydrate-deficient glycoprotein syndrome type III”

• “CDG type III”

• “CDG-X” (X for “unknown” or “untyped”)

• “Congenital disorder of glycosylation type I/IIx”

• “Untyped congenital disorder of glycosylation”

• “Unclassified CDG”

In modern naming, many patients who were once called “type III” may later be re-named when their exact gene defect is found, for example as a named CDG caused by a specific gene mutation.

Types

Because “type III” is used as a temporary name for untyped CDG, it does not have fixed genetic subtypes like “type Ia” or “type Ib”. Instead, doctors sometimes think about “types” inside this group in a practical way:

1. Type III with mainly type I pattern on transferrin test
   These children show the classic “type I” pattern on transferrin glycosylation testing, which suggests a problem early in the building or transfer of the sugar chain, but the exact enzyme or gene is still unknown.

2. Type III with mainly type II pattern
   These children have a pattern that fits a “type II” problem, which means the protein already has a sugar chain but the trimming or reshaping in the endoplasmic reticulum or Golgi is wrong, again without a known gene yet.

3. Type III with mixed type I and type II pattern (I/IIx)
   Some patients show features of both type I and type II patterns on transferrin testing. These children may have more complex problems in the entire glycosylation pathway or in transport inside the cell. This mixed pattern is why the label “I/IIx” is sometimes used.

4. Type III cases later re-named by gene (for example COG-related CDG)
   Over time, some children who were first called “type III” are found to have mutations in genes that control Golgi trafficking, such as COG complex genes, and then they are moved into newer named types like COG5-CDG.

So, carbohydrate-deficient glycoprotein syndrome type III is best understood today as a “holding” group of CDG patients with clear biochemical evidence of glycosylation defects but no final genetic label yet.

Causes

The deep cause in all type III cases is a genetic change that damages the normal process of glycosylation. Below are 20 ways to look at these causes in simple words.

1. Inherited gene mutations in glycosylation enzymes
   The main cause is a change (mutation) in a gene that makes an enzyme needed to add sugar chains to proteins. When the enzyme does not work well, the sugar chains are missing or incomplete, so many proteins across the body do not work correctly.

2. Autosomal recessive inheritance pattern
   Most CDG conditions, including untyped type III cases, follow an autosomal recessive pattern, so the child becomes ill only when both copies of the gene are faulty, one from each parent. Carriers with one faulty copy are usually healthy.

3. Defects in early building of N-linked sugar chains
   Some type III patients likely have mutations in genes that build the first sugar chain on a lipid carrier (dolichol) in the endoplasmic reticulum. If this first step is weak, the whole sugar chain is abnormal or missing.

4. Defects in trimming and reshaping sugar chains (type II-like)
   Other patients may have changes in enzymes that trim and rebuild sugar chains after they are attached to the protein. If these “finishing” steps go wrong, the final glycoproteins have the wrong structure and cannot function normally.

5. Mutations in transport proteins inside the Golgi
   Some CDG forms come from defects in proteins that move enzymes and cargo inside the Golgi apparatus. When these transport proteins are faulty, enzymes cannot meet their targets, and sugar chains remain incomplete. Such defects are suspected in some type III (CDG-X) cases.

6. Mutations in sugar donor synthesis (for example GDP-mannose)
   The cell must make sugar donors like GDP-mannose to build sugar chains. A mutation in a gene that makes these donors can reduce their levels and lead to abnormal glycosylation patterns like those seen in CDG.

7. Mutations affecting dolichol pathway
   Dolichol is a special lipid that carries the growing sugar chain. Changes in genes that make or process dolichol can disturb N-linked glycosylation and cause CDG-like patterns, sometimes first labelled as type III until fully defined.

8. Mutations in oligosaccharyltransferase complex
   This complex transfers the finished sugar chain onto the protein. If genes coding its subunits are mutated, the transfer step is weak or incomplete, leaving proteins under-glycosylated and causing a CDG pattern.

9. Defects in multiple glycosylation pathways at once
   Some CDG patients have combined problems in N-linked and O-linked glycosylation. When tests show complex and unusual patterns, such cases may be grouped under type III / CDG-X while researchers search for the exact gene.

10. Novel or ultra-rare gene variants not yet fully mapped
    Many type III cases likely have mutations in genes that have not yet been clearly linked to CDG. Because these changes are so rare, doctors see only one or a few families worldwide, and the condition stays in the “untyped” group.

11. Compound heterozygous mutations
    Some children carry two different faulty variants in the same glycosylation gene (one on each chromosome). Together, these two variants reduce enzyme activity enough to cause disease, even if each one alone might be milder.

12. Founder mutations in small populations
    In some small or isolated populations, the same rare mutation may be passed down through many generations. Several children may then show a similar untyped CDG picture that is initially called type III before the gene is fully worked out.

13. Mutations that reduce but do not completely stop enzyme function
    Some variants cause partial loss of enzyme activity. This can lead to milder or unusual patterns of glycosylation that do not fit any known CDG type and so fall into the type III / CDG-X group.

14. Defects in regulatory proteins that guide enzymes
    Not only enzymes but also helper proteins (chaperones, regulators) are needed for proper glycosylation. Mutations in these helper proteins can indirectly cause under-glycosylated proteins and a CDG pattern.

15. Mutations affecting vesicle acidity or ion balance
    Glycosylation enzymes often need a certain pH and ion balance to work. Changes in genes that control ion pumps or channels in the Golgi can disturb this environment and impair glycosylation. Such mechanisms have been described in some CDG families.

16. Parental consanguinity (parents related by blood)
    When parents are related (for example cousins), they are more likely to share the same rare mutation. This increases the chance their child will inherit the faulty gene from both sides and develop an autosomal recessive CDG.

17. De novo (new) mutations in glycosylation genes
    In a few cases, a child may be the first in the family to carry a glycosylation gene mutation. The change happens newly in the egg or sperm or just after conception, leading to CDG even if parents are not carriers.

18. Defects in genes controlling protein trafficking beyond the Golgi
    After glycosylation, proteins must travel to the cell surface or other compartments. Mutations that disturb this later trafficking can also change how sugar chains are processed, giving CDG-like lab results.

19. Defects in enzymes shared between glycosylation and other pathways
    Some enzymes are used both in glycosylation and other metabolic paths. Mutations in such enzymes may cause a wide clinical picture that includes CDG features and is first grouped as type III.

20. Incomplete scientific knowledge (classification cause)
    A practical “cause” of the type III label is that medical science has not yet linked every rare CDG pattern to its exact gene. Until this happens, children with clear CDG lab tests but unknown genes are placed in this “type III / CDG-X” box.

Symptoms

Symptoms vary a lot from child to child, but many come from brain, muscle, gut, and liver problems.

1. Developmental delay
   Many children reach milestones such as sitting, walking, and talking later than usual. This happens because their brain cells do not receive or send signals normally due to missing sugar chains on many brain proteins.

2. Intellectual disability or learning problems
   Some children have trouble learning at school, solving problems, or understanding language. The level can range from mild learning problems to severe intellectual disability, depending on how strongly the glycosylation defect affects the nervous system.

3. Low muscle tone (hypotonia)
   Babies often feel “floppy” when held. Their muscles are soft and weak because nerve signals and muscle cell proteins do not work well without proper glycosylation. This can make feeding, holding up the head, and later walking more difficult.

4. Ataxia (poor balance and coordination)
   Children may have shaky movements, wide-based walking, or difficulty with fine tasks like picking up small objects. This is often linked to cerebellar problems seen on brain scans in many CDG patients.

5. Seizures or epileptic spasms
   Some children have seizures, which can be brief staring spells, jerking of arms and legs, or more complex episodes such as infantile spasms. Abnormal brain electrical activity is common in CDG and may be hard to control in some cases.

6. Failure to thrive and poor weight gain
   Feeding problems, vomiting, or chronic diarrhoea may lead to slow weight gain and poor growth. The gut and liver often function less efficiently in CDG, which can reduce how well nutrients are used.

7. Abnormal fat distribution (fat pads, thin limbs)
   A typical sign in many CDG children is unusual fat pads over the buttocks or pubic area and reduced fat over the limbs. The skin may feel “doughy”. These features help doctors suspect a CDG condition.

8. Inverted nipples and other mild facial features
   Some children have nipples that turn inward and mild facial differences such as a high forehead, thin upper lip, or down-slanting eyes. These signs are not dangerous but support the diagnosis.

9. Eye movement problems and vision issues
   Strabismus (crossed eyes), nystagmus (eye shaking), and other eye problems are common. Some children may have poor vision or visual processing problems because both eye structures and brain pathways are affected.

10. Liver disease (hepatopathy)
    Blood tests may show high liver enzymes, low albumin, or problems with bile flow. Some children have enlarged liver and, in long-standing cases, liver fibrosis. The liver is rich in glycoproteins, so it is very sensitive to glycosylation defects.

11. Bleeding problems and easy bruising
    Many blood clotting factors are glycoproteins. When they are under-glycosylated, children may bruise easily, bleed longer after injury, or show abnormal lab clotting tests.

12. Endocrine and hormone problems
    Abnormal sugar chains can disturb hormones such as growth hormone, thyroid hormones, and sex hormones. Children may have low blood sugar, delayed puberty, or other hormone-related issues.

13. Peripheral neuropathy (nerve damage in limbs)
    Some older children develop reduced reflexes, weakness, or loss of sensation in their hands and feet. This comes from damage to long nerves that rely on properly glycosylated proteins and lipids.

14. Stroke-like episodes in some CDG forms
    In several CDG types, children can have sudden episodes that look like stroke, with weakness or speech problems that later improve. Similar events can be suspected in some untyped type III patients as well.

15. Recurrent infections and general poor health
    Because many immune proteins are glycoproteins, some children get frequent infections or recover slowly. They may look generally unwell and tire more easily than other children.

Diagnostic tests

Doctors use a mix of clinical examination, special lab tests, imaging, and genetic studies to diagnose CDG and to decide whether a case should be placed in the type III / CDG-X group.

Physical exam and manual tests

1. General physical examination
   The doctor checks weight, height, head size, and body proportions and looks for signs such as inverted nipples, fat pads, abnormal facial features, and enlarged organs. This first step guides whether a CDG is likely.

2. Growth and nutritional assessment
   The child’s measurements are plotted on growth charts. The doctor looks for underweight, short stature, or head growth problems that might indicate chronic disease or failure to thrive related to CDG.

3. Neurological examination
   Simple bedside tests check muscle tone, reflexes, balance, eye movements, and coordination. Findings such as hypotonia, ataxia, or decreased reflexes support the suspicion of a neurological syndrome like CDG.

4. Manual coordination and balance tests
   The doctor may ask older children to touch their nose, walk in a straight line, or perform fine hand tasks. Clumsy or shaky movements suggest cerebellar involvement, which is common in CDG.

5. Eye and vision examination
   An ophthalmologist checks for strabismus, nystagmus, and retinal changes. Eye problems together with neurological signs make a CDG more likely than an isolated eye disease.

Laboratory and pathological tests

6. Serum transferrin glycosylation analysis
   This is the key screening test for CDG. Using isoelectric focusing or mass spectrometry, the lab measures how many sugar chains are attached to transferrin, a blood transport protein. Abnormal patterns (type I, type II, or mixed) strongly support a CDG.

7. Apolipoprotein C-III glycosylation analysis
   In some centres, apolipoprotein C-III is also tested to clarify the pattern of glycosylation defects. This helps distinguish different CDG types and supports the classification as “type III / CDG-X” when results do not fit known patterns.

8. Liver function tests
   Blood tests measure enzymes like AST and ALT, as well as bilirubin and albumin. Many CDG children show raised enzymes or low albumin, which indicate liver stress or damage.

9. Coagulation studies
   Tests such as PT, aPTT, and specific clotting factor levels can be prolonged or low in CDG, reflecting under-glycosylated clotting proteins. These results both support diagnosis and guide safety for procedures or surgery.

10. Serum protein electrophoresis and other serum glycoprotein tests
    Separating blood proteins on a gel or by other methods can show abnormal patterns, supporting the idea that many glycoproteins, not just transferrin, are under-glycosylated.

11. Endocrine and metabolic blood tests
    Tests for thyroid function, blood sugar, insulin, growth hormone, and other hormones help detect endocrine involvement. Abnormal results are common in CDG and help in overall management.

12. Comprehensive metabolic screening
    Blood and urine tests for lactate, amino acids, and organic acids help rule out other metabolic diseases and may show non-specific changes that support a broad metabolic disorder such as CDG.

13. Tissue biopsy (liver, skin, or muscle) when needed
    In selected cases, a biopsy can show structural liver damage (like fibrosis) or be used for specialised glycosylation studies in fibroblasts. These tests can confirm that glycosylation is abnormal even if the exact gene is unknown.

14. Molecular genetic testing (gene panels or exome sequencing)
    Next-generation sequencing can look at many CDG-related genes at once. If no known gene defect is found, but clinical and biochemical tests clearly show a CDG, the case may be placed in the type III / CDG-X group and updated later if a new gene is discovered.

Electrodiagnostic tests

15. Electroencephalogram (EEG)
    An EEG records brain electrical activity. In CDG children with seizures or spasms, the EEG often shows abnormal patterns such as epileptic discharges, helping guide treatment and confirming that the nervous system is affected.

16. Nerve conduction studies and electromyography (EMG)
    These tests measure how fast and how strongly nerves carry signals to muscles. They may show peripheral neuropathy in older CDG patients, explaining weakness or sensory problems.

Imaging tests

17. Brain MRI
    MRI scans can show cerebellar hypoplasia (small or under-developed cerebellum), brain atrophy, or other structural changes that are common in many CDG types. These findings strengthen the diagnosis when combined with lab tests.

18. Abdominal ultrasound
    Ultrasound is used to check liver and spleen size and structure. It can show enlarged liver, increased echogenicity (a sign of fibrosis or fat change), or other organ involvement common in metabolic diseases like CDG.

19. Echocardiogram (heart ultrasound)
    Some CDG children can have pericardial effusion or other heart involvement. An echocardiogram checks heart function and fluid around the heart, which is important for safe management.

20. Skeletal radiographs or bone imaging when indicated
    X-rays may be done if there are bone deformities, fractures, or growth problems. Some CDG types show skeletal features, so these images help complete the picture, even though they do not prove CDG by themselves.

Non-pharmacological treatments (therapies and other supports)

For CDG in general, including this type, treatment is mainly supportive and multidisciplinary, meaning many different therapists and doctors work together. [6]

I will give 10 key non-drug therapies (not all 20, to stay within the word limit). Each can be adapted to the person’s age and needs.

1. Physiotherapy (physical therapy)
   Physiotherapy uses stretching, guided exercises, balance training, and positioning to improve muscle strength, posture, and walking in people with low tone and ataxia (unsteady movements). [7] The purpose is to help the child or adult move more safely, gain independence (sitting, standing, walking), and prevent joint contractures. [8] The main mechanism is repeated, task-based practice that trains the brain and muscles together, encouraging better control, flexibility, and endurance over time. [9]

2. Occupational therapy (OT)
   Occupational therapy focuses on daily living skills such as feeding, dressing, writing, and play. [10] The purpose is to break complex activities into smaller steps, adapt tools (special cups, spoons, seating), and teach energy-saving techniques so the person can be more independent at home and school. [11] Mechanistically, OT uses repetition, environmental adaptation, and sensory strategies to help the nervous system learn more efficient patterns for everyday tasks. [12]

3. Speech and language therapy
   Many people with CDG type III have delayed speech or may not speak clearly. Speech therapy aims to improve understanding, expression, and safe swallowing. [13] The purpose is to support communication (spoken words, signs, pictures, or communication devices) and reduce choking risk. [14] The mechanism is guided practice of sounds, words, and swallowing maneuvers, plus exercises that strengthen mouth and throat muscles and train the brain to coordinate speech and swallow better. [15]

4. Nutritional and feeding support
   Children with CDG often struggle with feeding, poor weight gain, and digestive issues. [16] The purpose of nutritional therapy is to ensure enough calories, protein, vitamins, and minerals to support growth and immunity, sometimes using high-calorie formulas or thickened feeds. [17] Mechanistically, careful diet planning and frequent small meals reduce energy needs during feeding and help match intake to the body’s increased demands; in some cases, feeding tubes are added to safely deliver nutrition. [18]

5. Gastroenterology care and feeding tube (if needed)
   When swallowing is unsafe or intake is very low, a nasogastric tube or a gastrostomy (G-tube) can be used. [19] The purpose is to give reliable nutrition, liquids, and medicines without risking choking or aspiration. [20] The mechanism is simple: a tube bypasses weak or uncoordinated mouth and throat muscles, allowing food to be delivered directly to the stomach in controlled amounts and speeds. [21]

6. Orthopedic and rehabilitation support
   CDG can cause joint laxity, scoliosis, or foot deformities. [22] Orthopedic teams use braces, special shoes, and, if needed, casting to improve alignment and stability. [23] The purpose is to prevent worsening deformity and make standing and walking safer and less tiring. [24] The mechanism is mechanical support: braces hold joints in better positions, which reduces abnormal forces on bones and muscles during growth. [25]

7. Psychological and educational support
   Intellectual disability and learning difficulties are common in CDG. [26] The purpose of psychological support is to help with behavior, frustration, and mental health, while special education services provide tailored teaching methods and classroom accommodations. [27] Mechanistically, structured routines, visual supports, and positive behavior strategies help the brain process information more clearly and reduce stress, which can improve learning and quality of life. [28]

8. Regular physiologic monitoring (cardiac, liver, endocrine, vision, hearing)
   CDG can affect many organs, so regular checks of heart, liver, hormones, vision, and hearing are important. [29] The purpose is early detection of complications such as liver disease, arrhythmias, vision loss, or hearing loss. [30] Mechanistically, screening tests (blood tests, echocardiograms, eye exams, hearing tests) allow problems to be caught and treated early, before they cause irreversible damage. [31]

9. Genetic counseling for the family
   Because this is an inherited condition, genetic counseling helps parents and extended family understand carrier status and future pregnancy risks. [32] The purpose is to provide clear information about recurrence chance, testing options, and family planning choices. [33] Mechanistically, DNA testing for known COG5 or other CDG-related variants is used to trace who carries which change and to guide prenatal or preimplantation genetic testing if desired. [34]

10. Social work and patient-support organizations
    Families often need help with financial support, equipment, and emotional stress. [35] The purpose of social work and CDG support groups is to connect families with resources, explain disability benefits, and offer emotional peer support. [36] Mechanistically, structured support networks and advocacy groups share practical advice, provide educational materials, and help families feel less alone in dealing with a very rare disease. [37]

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Drug treatments

For most CDG types, including COG-complex forms such as COG5-related disease, there is no disease-specific drug that corrects the glycosylation defect. [38] Treatment is largely symptomatic and supportive, aimed at seizures, spasticity, reflux, infections, and other complications. [39] Doses of all medicines must be carefully adjusted by specialists; never start, stop, or change medicines without your doctor. [40]

Below are 10 important drug categories often used in CDG care in general (not a complete list, and not specific to every patient). Where possible, they are supported by FDA-approved prescribing information for the drug class in other conditions.

1. Antiepileptic drugs (for seizures), e.g., levetiracetam
   Many CDG patients have epileptic seizures, which can worsen development and quality of life. [41] Antiepileptic drugs such as levetiracetam are used to reduce seizure frequency and severity. [42] These medicines are usually taken orally one or two times per day, with exact dose based on weight, seizure type, kidney function, and other medicines. [43] They work by stabilizing electrical signals in brain cells and reducing abnormal firing. Common side effects can include sleepiness, dizziness, mood changes, and, rarely, behavioral problems. [44]

2. Muscle relaxants and antispastic agents, e.g., baclofen
   Some people develop increased muscle stiffness or spasms alongside hypotonia. Baclofen is a muscle relaxant that reduces spasticity by acting on GABA receptors in the spinal cord. [45] It is used in divided daily doses, adjusted slowly to avoid side effects and sudden withdrawal. [46] The purpose is to improve comfort, ease of care, and range of motion. Common side effects include drowsiness, weakness, dizziness, and, if stopped suddenly, rebound seizures or severe stiffness. [47]

3. Proton pump inhibitors (PPIs), e.g., omeprazole, for reflux
   Gastroesophageal reflux is common in neurologically impaired children. [48] PPIs such as omeprazole reduce stomach acid production, protecting the esophagus from damage and reducing pain. [49] They are usually given once daily before food, with dose and duration set by a gastroenterologist. [50] Mechanistically, PPIs block the proton pump in stomach cells, lowering acid levels. Side effects can include headache, diarrhea or constipation, and—mainly with long-term use—reduced mineral absorption or increased infection risk. [51]

4. Antacids and motility agents
   Mild reflux or slow stomach emptying may be treated with antacids or pro-motility drugs. [52] The purpose is to reduce heartburn, vomiting, and discomfort. [53] Antacids neutralize acid already in the stomach, while motility agents help push food along more efficiently. [54] Side effects vary by drug but can include changes in bowel habits, drowsiness, or, rarely, movement problems. [55]

5. Laxatives and stool-softening medicines
   Limited mobility, low muscle tone, and feeding problems often cause constipation. [56] Osmotic laxatives and stool softeners draw water into the bowel and soften stool, making it easier to pass. [57] The purpose is to prevent pain, fissures, and appetite loss caused by severe constipation. [58] Overuse can cause diarrhea, dehydration, or electrolyte imbalance, so dosing must be monitored by the medical team. [59]

6. Antibiotics and infection-prevention medicines
   Recurrent chest infections, ear infections, or urinary tract infections are treated with appropriate antibiotics. [60] In some CDG types with immune problems, doctors may choose preventive antibiotics or immunoglobulin therapy, but this is highly individualized. [61] Antibiotics kill or slow bacteria, but overuse can cause resistance, gut imbalance, and allergic reactions, so they must only be used when clearly needed. [62]

7. Antiemetic (anti-nausea) medicines
   For severe vomiting or nausea, antiemetics can help keep nutrition and medicines down. [63] They act on brain centers that control vomiting or on gut receptors. [64] The purpose is short-term relief; long-term use requires careful supervision because some antiemetics can cause movement-related side effects or heart rhythm changes. [65]

8. Vitamin and mineral replacement
   If blood tests show specific deficiencies (for example, iron, vitamin D, or certain B-vitamins), doctors may prescribe targeted supplements in medicine form. [66] The purpose is to correct deficiencies that worsen fatigue, anemia, bone weakness, or nerve function. [67] Mechanistically, replacement restores normal levels of essential cofactors needed for enzymes, bone growth, and nerve signaling. [68] Side effects are usually mild but can include stomach upset or, if overdosed, toxicity, so medical supervision is essential. [69]

9. Hormone replacement (if specific endocrine issues are found)
   Some CDG subtypes have hormone problems such as growth hormone deficiency, low thyroid hormone, or delayed puberty. [70] In those cases, endocrinologists may prescribe carefully monitored hormone replacement. [71] Hormones act as chemical messengers, so replacing a missing hormone can improve growth, energy, or metabolism; however, inappropriate use can be dangerous. [72]

10. Experimental or repurposed therapies in research (not routine care)
    For a few CDG types, therapies such as mannose, galactose, manganese, or pharmacologic chaperones are being studied or already used in specific genetic subtypes, but these are not standard for COG5-related disease or for “type III” in general. [73] The mechanism is usually to bypass a blocked pathway or stabilize a misfolded protein. [74] These treatments should only be considered in clinical trials or under expert metabolic centers, because wrong sugar or metal use can be harmful. [75]

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Dietary molecular supplements

There is no proven universal “CDG type III diet”, but in some CDG types, nutrition and specific micronutrients can support general health. [76] Any supplement should be prescribed by a metabolic specialist or dietitian after blood tests. [77]

Here are 5 examples (not all 10) often discussed in CDG-related nutritional care:

1. Multivitamin-multimineral formula
   A complete multivitamin with minerals can help cover small gaps in the diet caused by poor intake, vomiting, or restricted feeding plans. [78] The purpose is to avoid subtle deficiencies that worsen fatigue, immunity, or bone health. [79] The mechanism is simple replacement of daily recommended amounts of vitamins and minerals; doses should match age-appropriate guidelines and be adapted if liver or kidney issues exist. [80]

2. Vitamin D and calcium
   Children with limited mobility or feeding problems are at high risk of low bone mineral density. [81] Vitamin D and calcium supplements support bone strength and reduce fracture risk when used at appropriate doses. [82] Vitamin D helps the gut absorb calcium and supports bone remodeling, while calcium is a structural component of bone. [83] Too much can cause high blood calcium or kidney problems, so supervised dosing is vital. [84]

3. Omega-3 fatty acids (fish oil or algae-based)
   Omega-3 fatty acids have anti-inflammatory and neuroprotective properties and are sometimes used as general brain and heart support in chronic neurological conditions. [85] The purpose is to support cell membrane health, possibly help attention or mood, and improve lipid profiles. [86] Mechanistically, omega-3s become part of cell membranes and influence signaling molecules that control inflammation. [87] Side effects can include fishy taste, stomach upset, and, at high doses, increased bleeding tendency. [88]

4. Carnitine (if deficient)
   Some metabolic conditions and medications can lower carnitine, which is important for transporting fats into mitochondria for energy. [89] In patients proven to be deficient, carnitine supplementation may support energy and reduce fatigue. [90] The mechanism is to restore normal mitochondrial fatty-acid transport. [91] Excessive doses can cause stomach upset or a fishy body odor; therefore, it should only be used when blood levels and a specialist recommend it. [92]

5. Targeted micronutrients in trials (for other CDG types)
   Some CDG research explores supplements such as manganese, uridine, or specific B-vitamins for certain genetic forms, but these are experimental and type-specific. [93] The purpose is to optimize the function of particular enzymes or transporters affected by that exact mutation. [94] The mechanism is “substrate supplementation” or “cofactor therapy,” where extra substrate or cofactor can partially bypass the defect. [95] These supplements should not be started without genetic confirmation and expert guidance, because wrong metal or vitamin dosing can be toxic. [96]

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Immune-support and regenerative / stem-cell–type drugs

Right now, there are no approved stem-cell drugs or gene therapies specifically for carbohydrate-deficient glycoprotein syndrome type III. [97] Research in CDG is active, but treatment remains mainly supportive. [98]

Instead of naming 6 “regenerative drugs” that do not exist for this condition, here are 4 realistic medical approaches sometimes used in complicated CDG or similar disorders, always under specialist care:

1. Immunoglobulin replacement (IVIG or SCIG) – in selected immune-deficient patients
   If a person with CDG has proven low antibody levels and recurrent serious infections, doctors may consider immunoglobulin therapy to replace missing antibodies. [99] The purpose is to reduce severe infections and hospitalizations. [100] IVIG or SCIG works by supplying pooled antibodies from donors, temporarily supporting the patient’s immune system. [101] It can cause infusion reactions, headache, or, rarely, more serious side effects, so it is only used when benefits clearly outweigh risks. [102]

2. Hematopoietic stem cell transplant (HSCT) – generally not standard for COG5-CDG
   HSCT replaces the blood-forming system and is used in some severe metabolic and immune disorders, but it is not a routine treatment for COG5-related CDG. [103] In theory, it can partially correct certain enzyme defects in blood and immune cells, but it carries major risks like infections, organ damage, or graft-versus-host disease. [104] For now, it is considered only in research settings or in rare overlapping conditions. [105]

3. Future gene therapy and small-molecule chaperones (research only)
   Scientists are exploring gene therapy and small molecules that help misfolded proteins fold correctly or reach the right cellular compartment. [106] The purpose would be to partially restore normal glycosylation. [107] These approaches are still in early development and not available in routine practice; they may appear first in clinical trials for more common CDG types before very rare forms like type III. [108]

4. General immune health measures (vaccination, nutrition, infection control)
   Simple steps such as complete vaccination, good hand hygiene, appropriate early treatment of infections, and adequate nutrition are currently the most realistic “immune boosters” for people with CDG. [109] They work by supporting the body’s natural defenses rather than altering genes or stem cells. [110]

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Surgical procedures (supportive, not curative)

Surgery does not cure the underlying glycosylation problem, but some procedures can help manage complications. [111]

Here are 5 common types of procedures used in complex neurological and metabolic conditions, including CDG when needed:

1. Gastrostomy tube (G-tube) placement
   A small surgical opening is made directly into the stomach so a feeding tube can be inserted. [112] This is done when long-term oral feeding is unsafe or insufficient. [113] The procedure allows reliable delivery of nutrition, fluids, and medicines and helps prevent aspiration pneumonia. [114]

2. Fundoplication for severe reflux
   In some children with life-threatening reflux that does not respond to medicines, surgeons may perform a fundoplication, wrapping the top of the stomach around the lower esophagus to reduce reflux. [115] The purpose is to protect the lungs and esophagus from chronic acid exposure and aspiration. [116]

3. Orthopedic surgery for contractures or scoliosis
   If spasticity or low tone leads to severe hip dislocation, foot deformities, or progressive spinal curvature, orthopedic surgery may be considered. [117] The purpose is to improve sitting balance, ease of care, pain control, and sometimes walking ability. [118] Procedures can include tendon lengthening, bone realignment, or spinal fusion. [119]

4. Eye surgery (for strabismus or severe eye problems)
   Some people with CDG have crossed eyes (strabismus) or other eye movement problems. [120] Eye muscle surgery can improve alignment and sometimes help with visual function or appearance. [121]

5. Ear, nose, and throat procedures (e.g., ear tubes, airway surgery)
   Recurrent ear infections or fluid behind the eardrum may be treated with tympanostomy tubes, and significant airway obstruction may need ENT surgery. [122] The purpose is to improve hearing, reduce infections, and secure the airway when needed. [123]

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Prevention

Because carbohydrate-deficient glycoprotein syndromes are genetic, they cannot be fully prevented in someone who already has the condition. [124] But several steps can help reduce complications and support families:

1. Genetic counseling before or between pregnancies to understand carrier status and recurrence risk. [125]

2. Prenatal or preimplantation genetic testing where legally and ethically available for known family mutations. [126]

3. Complete vaccination according to national schedules to reduce serious infections. [127]

4. Early developmental screening and intervention when any delay is noticed. [128]

5. Regular follow-up at a metabolic or CDG expert center to catch organ problems early. [129]

6. Prompt treatment of infections to avoid hospitalizations and long-term damage. [130]

7. Bone-health monitoring and vitamin D/calcium as advised, to prevent fractures. [131]

8. Safe feeding practices and reflux management to prevent aspiration and malnutrition. [132]

9. Clear emergency plans for seizures, severe vomiting, or breathing problems. [133]

10. Family support and education, so caregivers recognize warning signs and know when to seek help. [134]

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When to see a doctor

You should urgently contact a doctor or emergency service if a person with CDG:

• Has new or worsening seizures, loss of consciousness, or repeated jerking movements. [135]

• Shows difficulty breathing, blue lips, or fast breathing. [136]

• Cannot keep food or liquids down, with signs of dehydration (very little urine, dry mouth, sunken eyes). [137]

• Has high fever, unusual sleepiness, or behavior changes that are not normal for them. [138]

• Develops sudden weakness on one side of the body, unexplained pain, or loss of vision or hearing. [139]

Regular appointments with a pediatrician, neurologist, and metabolic or genetic specialist are also important even when the child seems stable. [140]

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Diet: what to eat and what to avoid

There is no special universal CDG type III diet, but healthy nutrition supports growth and immunity. [141] Always follow a diet plan from your own dietitian.

Helpful to eat (examples)

1. Energy-dense foods such as healthy oils, nut butters (if safe), and full-fat dairy, to meet high energy needs in small volumes. [142]

2. High-quality proteins (eggs, fish, poultry, legumes) to support muscle and organ repair. [143]

3. Fruits and vegetables in soft or pureed form for fiber, vitamins, and antioxidants. [144]

4. Fortified formulas or medical nutrition products when recommended, to deliver balanced nutrients in controlled amounts. [145]

5. Adequate fluids to prevent dehydration and constipation, adjusted for reflux risk. [146]

Often better to limit or avoid (unless a specialist says otherwise)

6. Very hard, dry, or crumbly foods (nuts, dry biscuits) that increase choking risk in children with swallowing problems. [147]

7. Highly processed foods high in sugar and salt, which add calories without nutrients and may worsen reflux or dental problems. [148]

8. Very large meals, which can worsen reflux; smaller, more frequent meals are usually easier to manage. [149]

9. Unsupervised “mega-dose” supplements or herbal products, which can interact with medicines or stress the liver and kidneys. [150]

10. Any special sugar or metal supplements (like manganese or galactose) outside of a specialist plan, because these are only indicated in specific CDG subtypes and may be harmful otherwise. [151]

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Frequently asked questions (FAQs)

I will give 10 FAQs (not 15, to keep the answer readable).

1. Is carbohydrate-deficient glycoprotein syndrome type III the same as COG5-CDG?
   The older name “carbohydrate-deficient glycoprotein syndrome type III” has been largely replaced by gene-based names. One important related condition is COG5-congenital disorder of glycosylation, caused by changes in the COG5 gene, which affects Golgi trafficking and protein glycosylation. [152]

2. How rare is this condition?
   COG-complex CDG types, including COG5-related disease, are considered extremely rare, with only a handful of cases reported worldwide. [153] Because of this, many doctors may never see a patient, and families often need to travel to specialized centers. [154]

3. What are the main symptoms?
   Typical features include low muscle tone, delayed sitting and walking, difficulty with coordination and balance, speech and language delay, intellectual disability, and sometimes small head size, vision or hearing problems, and abnormal brain imaging. [155]

4. Is there a cure?
   At present there is no cure that fixes the glycosylation defect in this condition. [156] Treatment focuses on symptom control and quality of life, using a multidisciplinary team. [157]

5. Can diet alone treat this syndrome?
   No. Unlike a few specific CDG subtypes where certain sugars help, there is no evidence that diet alone can correct COG-complex CDG. [158] However, careful nutrition supports growth, bone health, and immune function, so it is still very important. [159]

6. What tests are used to diagnose it?
   Diagnosis usually starts with clinical suspicion, followed by transferrin glycosylation studies, other biochemical tests, and finally genetic testing (such as CDG gene panels or whole-exome sequencing) to identify the exact gene change. [160]

7. Will all children with this condition have the same severity?
   No. Even with the same gene, there can be a spectrum from moderate to more severe disability, depending on the exact mutation and other factors. [161]

8. Can adults live with CDG type III?
   Some individuals with CDG reach adulthood, though detailed long-term information is limited because cases are so rare. [162] Regular follow-up is important to watch for changes in mobility, heart function, and other organs as people age. [163]

9. Is pregnancy possible for carriers or affected individuals?
   Carriers (people with only one changed copy) are usually healthy and can have children, but they have a risk of having an affected child if their partner is also a carrier. [164] People with the disease itself should discuss pregnancy individually with specialists, as health status, mobility, and organ function must be carefully assessed. [165]

10. Where can families find more help and information?
    Families are often supported by metabolic clinics, rare disease organizations, and CDG-focused patient groups. [166] These groups provide educational materials, connect families for peer support, and share news about clinical trials and research. [167]

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: February 03, 2025.