ALG12-CDG (CDG-Ig) is a rare, inherited disease that affects how the body adds sugar chains to proteins. This sugar-adding process is called glycosylation. In ALG12-CDG, a gene named ALG12 does not work correctly. The ALG12 protein’s normal job is to put the eighth mannose sugar onto a growing sugar chain inside the cell. When ALG12 does not work, many proteins are made with incomplete sugars, so they cannot do their jobs well. Because many organs need these sugar-coated proteins, many body systems can be involved—brain, nerves, muscles, immune system, blood clotting, bones, heart, kidneys, eyes, and more. ALG12-CDG is autosomal recessive, which means a child gets one non-working copy of the ALG12 gene from each parent. cdghub.com+3MedlinePlus+3NCBI+3
Common features include developmental delay, low muscle tone, seizures, small head size, unusual facial appearance, low antibody (IgG) levels with frequent infections, and clotting factor problems. Some children have skeletal changes and, less often, heart muscle weakness. Signs usually begin in infancy. PMC+4MedlinePlus+4PubMed+4
Carbohydrate-deficient glycoprotein syndrome type Ig is a very rare, inherited metabolic disease. Today doctors usually call it ALG12-CDG. It happens when a gene named ALG12 does not work properly. This gene makes an enzyme that builds a sugar chain (called an N-glycan) that must be attached to many proteins in our cells. The ALG12 enzyme adds the eighth mannose sugar to this growing chain inside the endoplasmic reticulum (the cell’s protein factory). When ALG12 is not working, many proteins are “under-glycosylated,” meaning they are missing sugars. Missing sugars can change protein shape and function all over the body, so many organs can be affected—especially the brain, muscles, immune system, and growth. ALG12-CDG is autosomal recessive. That means a child gets one faulty copy of the gene from each carrier parent. Signs usually start in infancy. Typical problems include weak muscle tone (hypotonia), developmental delay, feeding problems, poor weight gain, small head size (microcephaly), distinctive facial features, low antibody levels (especially IgG, causing frequent infections), and sometimes bleeding problems from low clotting factors. Orpha.net+4cdghub.com+4PubMed+4
Historical note: The first patients with ALG12-CDG were described in 2002. Before that, these conditions were grouped under “carbohydrate-deficient glycoprotein syndromes (CDGS).” PubMed+1
Other names
Doctors and families may see several names that mean the same condition:
ALG12-CDG (preferred modern name)
Congenital disorder of glycosylation type Ig (CDG-Ig)
Carbohydrate-deficient glycoprotein syndrome type Ig (CDGS-Ig) (older term)
Alpha-1,6-mannosyltransferase congenital disorder of glycosylation
ALG12 mannosyltransferase deficiency cdghub.com+2MedlinePlus+2
Types
There are no official “sub-types” within ALG12-CDG. Instead, ALG12-CDG is one member of the large CDG Type I group (problems in building or transferring the sugar chain). In classifications, Type Ig specifically equals ALG12-CDG. People with ALG12-CDG can have a spectrum of severity—from moderate developmental issues to severe multi-organ disease. Some studies also note a “dual” biochemical behavior (features of both Type I and II patterns on detailed glycan testing), but clinically it is still referred to as a Type I (Ig) disorder. Wikipedia+1
Causes
Biallelic pathogenic variants in ALG12 (one from each parent) are the root cause. These variants can be missense, nonsense, frameshift, or splice-site changes that reduce or abolish enzyme activity. PubMed+1
Loss of ALG12 enzyme function blocks addition of the eighth mannose to the lipid-linked oligosaccharide, stalling correct N-glycan assembly. Wikipedia
Under-glycosylation of many proteins in the body leads to multi-system illness (brain, muscle, immune, clotting). JCI+1
Autosomal recessive inheritance: having two faulty copies is required; carriers are usually healthy. MedlinePlus
Consanguinity (parents related by blood) can increase the chance both parents carry the same rare variant. (General genetic principle for rare recessive diseases.) fcdgc.rarediseasesnetwork.org
Enzyme misfolding from certain missense variants can make the protein unstable or quickly degraded. (Mechanism inferred in many CDG enzymes.) JCI
Defective ER mannose transfer specifically impairs N-glycosylation steps inside the endoplasmic reticulum. Wikipedia
Abnormal glycosylation of immunoglobulins (especially IgG) contributes to low IgG levels and infections. NCBI
Abnormal glycosylation of coagulation factors contributes to bleeding or easy bruising. Orpha.net
Disrupted brain development due to many neural proteins being under-glycosylated, leading to microcephaly and developmental delay. fcdgc.rarediseasesnetwork.org
Neuromuscular involvement from poor glycosylation of muscle-related proteins, causing hypotonia. fcdgc.rarediseasesnetwork.org
Feeding/gastrointestinal dysfunction because gut and swallowing muscles and control pathways are affected. MedlinePlus
Growth failure (“failure to thrive”) due to high energy demands, feeding challenges, and systemic disease burden. MedlinePlus
Skeletal findings in some patients (e.g., skeletal dysplasia) likely reflect abnormal glycosylation in cartilage/bone proteins. fcdgc.rarediseasesnetwork.org
Hearing loss may appear when inner-ear proteins are under-glycosylated. fcdgc.rarediseasesnetwork.org
Eye problems (ocular abnormalities) can occur because vision-related proteins also need proper glycans. fcdgc.rarediseasesnetwork.org
Cardiac involvement (structural or functional) is reported in some patients. fcdgc.rarediseasesnetwork.org
Hydronephrosis/renal issues have been described in case reports, showing kidney involvement in certain families. NCBI
Variant-specific effects: different mutations can cause different residual activity and different severities (“genotype–phenotype” variation). ScienceDirect
Early-life vulnerability: because glycosylation is vital from the start of life, problems usually appear in infancy. MedlinePlus
(In short: the single fundamental cause is faulty ALG12; the other “causes” listed describe how this defect leads to system-wide problems and which contexts/variants raise risk or shape severity.)
Common symptoms and signs
Developmental delay – slower progress in sitting, standing, walking, and speaking because the brain and muscles do not work at full strength. fcdgc.rarediseasesnetwork.org
Hypotonia (low muscle tone) – “floppy” muscles and weak posture due to impaired muscle and nerve protein function. fcdgc.rarediseasesnetwork.org
Progressive microcephaly – head size becomes small for age as growth of the brain is affected. fcdgc.rarediseasesnetwork.org
Feeding difficulty – trouble sucking, swallowing, or coordinating feeding; may need special feeding plans. MedlinePlus
Failure to thrive – poor weight gain or slow growth from feeding issues and high energy needs. MedlinePlus
Recurrent respiratory infections – frequent colds, ear infections, or pneumonia because IgG is low and does not fight germs well. fcdgc.rarediseasesnetwork.org+1
Facial dysmorphism – features like prominent forehead, large ears, thin upper lip, which help doctors suspect a CDG. Orpha.net
Coagulation problems – easy bruising or bleeding due to reduced glycosylation and levels of clotting factors. Orpha.net
Intellectual disability – learning difficulties of varying degree due to brain involvement. fcdgc.rarediseasesnetwork.org
Seizures – may occur in some patients because abnormal glycosylation affects neuronal networks. PMC
Male genital hypoplasia – under-development of male genitalia noted in some boys. fcdgc.rarediseasesnetwork.org
Hearing loss (sensorineural) – trouble hearing because inner-ear structures are affected. fcdgc.rarediseasesnetwork.org
Eye problems – such as strabismus or other ocular issues; eye checks are important. fcdgc.rarediseasesnetwork.org
Cardiac abnormalities – structure or rhythm issues in some patients; screening is advised. fcdgc.rarediseasesnetwork.org
Distinct immune profile (hypogammaglobulinemia) – especially low IgG measured on blood tests. NCBI
Diagnostic tests
A) Physical examination
Growth and head-circumference charting – measures height, weight, and head size over time; failure to thrive and microcephaly point toward a congenital metabolic disorder like ALG12-CDG. MedlinePlus+1
Neurologic and tone assessment – checking posture, tone, reflexes, and milestones; hypotonia and delay raise suspicion for CDG. fcdgc.rarediseasesnetwork.org
Dysmorphology exam – looks for facial features (prominent forehead, large ears, thin upper lip) that often occur in ALG12-CDG. Orpha.net
Signs of bleeding – bruises, nosebleeds, or prolonged bleeding that suggest a clotting factor issue. Orpha.net
General systems review – heart sounds, chest exam (recurrent infections), abdomen (organ size), joints, and skin to capture multi-system disease. fcdgc.rarediseasesnetwork.org
B) Manual/bedside tests
Feeding/swallowing assessment – bedside checks by speech-language or feeding therapists to assess safety and efficiency; problems are common. MedlinePlus
Hearing screening (otoacoustic emissions/bedside audiology) – early detection of sensorineural hearing loss. fcdgc.rarediseasesnetwork.org
Vision screening – eye alignment and tracking to flag ocular abnormalities. fcdgc.rarediseasesnetwork.org
C) Laboratory and pathological tests
Serum transferrin isoelectric focusing (TIEF) or LC-MS transferrin glycoform analysis – the front-line biochemical screen for CDG. In Type I disorders (including ALG12-CDG), patterns show decreased fully glycosylated transferrin with increased under-glycosylated forms. JCI+1
N-glycan profiling of serum and/or IgG by mass spectrometry – defines the exact glycan “fingerprint,” and ALG12-CDG shows characteristic under-mannosylated patterns; in some reports, features of both Type I and II can appear. NCBI
Quantitative immunoglobulins – often low IgG (hypogammaglobulinemia). This explains frequent infections and guides therapy (e.g., IVIG consideration). NCBI
Coagulation panel – PT/INR, aPTT, and specific clotting factor levels (e.g., antithrombin, protein C/S, FV, FVIII). Many CDG show decreased glycosylated factors. Orpha.net
Comprehensive metabolic panel and liver tests – to check liver involvement (enzymes, proteins) which can occur in CDG. JCI
Genetic testing of the ALG12 gene – targeted sequencing or exome/genome testing confirms the diagnosis by finding two pathogenic variants. ScienceDirect
Carrier testing for parents and at-risk relatives – clarifies inheritance, reproductive risk, and counseling. (Standard practice in autosomal recessive CDG.) MedlinePlus
Newborn or infant expanded panels (where available) – some centers add CDG screens or rapid exome if early signs are present. (General CDG practice trend.) JCI
D) Electrodiagnostic tests
EEG – looks for seizure activity or abnormal background if spells or developmental regression occur. (Seizures reported in ALG12-CDG case literature.) PMC
EMG/NCS (electromyography/nerve conduction studies) – used when weakness or neuropathy is suspected; helps separate central vs peripheral contributions to hypotonia. (General neuromuscular evaluation in CDG.) JCI
E) Imaging tests
Brain MRI – assesses microcephaly, delayed myelination, cerebellar or cerebral atrophy, or structural anomalies that support a congenital glycosylation disorder. (Imaging is standard in CDG neurological work-ups.) JCI
System-focused imaging – echocardiogram for heart issues, renal ultrasound for kidney anomalies (e.g., hydronephrosis in some ALG12-CDG families), skeletal surveys if dysplasia suspected, and ophthalmic imaging as needed. fcdgc.rarediseasesnetwork.org+1
Non-Pharmacological Treatments (Therapies & Others)
Care coordination with a metabolic/clinical genetics team; this sets a detailed plan across systems. NCBI
Physiotherapy to improve tone, posture, balance, and motor skills; prevents contractures. NCBI
Occupational therapy for daily activities (feeding, dressing), hand skills, and adaptive tools. NCBI
Speech and feeding therapy for safe swallowing, communication, and language. NCBI
Nutritional support (high-calorie plans; thickened feeds) to sustain growth and immunity. MedlinePlus
Spine management (bracing, seating systems) to slow scoliosis/kyphosis progression. NCBI
Hearing support (hearing aids; classroom acoustics) if loss is present. fcdgc.rarediseasesnetwork.org
Vision therapy and glasses where helpful for tracking and reading. PMC
Seizure safety planning (sleep hygiene, trigger avoidance, rescue plan). MedlinePlus
Infection prevention routines (hand hygiene, prompt care plans). Frontiers
Vaccination per specialist advice (may tailor schedule if IgG is very low). Frontiers
Dental care to reduce infection risk and support feeding comfort. MedlinePlus
Physical medicine equipment (standing frames, AFOs, walkers) to build strength safely. NCBI
Educational supports/IEP to match learning needs and communication style. MedlinePlus
Mental health support for stress, anxiety, and family coping. BioMed Central
Social work support for home services, transport, benefits, and respite care. BioMed Central
Thrombosis prevention around procedures (hydration, line care, mobilization). CDG UK
Bone health plan (weight-bearing, safe sunlight, diet, and monitoring). PMC
Cardiac lifestyle (salt moderation, activity as tolerated, illness precautions). PMC
Palliative care when needed to improve comfort and quality of life across stages. BioMed Central
Drug Treatments
(Purpose, usual class, simple dosing guidance, mechanism, key cautions. Always individualize with a specialist. Doses below are typical references; not medical advice.)
Immunoglobulin replacement (IVIG or SCIG) – for low IgG with infections. Class: pooled antibodies. Dose: IVIG often 400–600 mg/kg every 3–4 weeks; SCIG weekly per product. Purpose: raise IgG. Mechanism: provides ready-made antibodies. Side effects: headache, fever, infusion reactions, rare thrombosis—monitor. Frontiers
Levetiracetam – seizure control. Class: antiseizure. Dose: commonly 20–60 mg/kg/day in divided doses. Mechanism: modulates synaptic release. Side effects: sleepiness, mood change. MedlinePlus
Valproate – alternative antiseizure (avoid if liver disease). Class: antiseizure. Dose: 10–60 mg/kg/day titrated. Mechanism: increases GABA; broad-spectrum. Side effects: weight gain, tremor, liver/pancreas risk—specialist monitoring required. MedlinePlus
Rescue benzodiazepine (diazepam/buccal midazolam) for prolonged seizures. Mechanism: enhances GABA. Side effects: drowsiness, breathing depression—follow emergency plan. MedlinePlus
Empiric/targeted antibiotics during infections. Class: varies by source. Dose: per guideline. Purpose: treat bacterial infections promptly. Side effects: GI upset, allergy, resistance. Frontiers
Prophylactic antibiotics (e.g., TMP-SMX low dose) in recurrent bacterial infections after immunology review. Mechanism: suppresses common organisms. Risks: allergy, cytopenias—specialist plan required. Frontiers
ACE inhibitor for proteinuria or heart support (e.g., enalapril). Class: RAAS blocker. Dose: often 0.1–0.5 mg/kg/day, titrate. Purpose: reduce protein leak, support heart. Mechanism: vasodilation and reduced intraglomerular pressure. Side effects: cough, high potassium, kidney effects—monitor. PMC
Beta-blocker for cardiomyopathy (e.g., carvedilol). Class: beta-blocker. Dose: pediatric start low, titrate by cardiology. Purpose: improve heart function and symptoms. Mechanism: lowers adrenergic stress. Side effects: low heart rate, fatigue, low BP. cardiologyres.org
Diuretics (furosemide) for edema or heart failure symptoms. Mechanism: increases urine to reduce fluid. Risks: electrolyte loss—monitor. PMC
Corticosteroids (for nephrotic-type presentations if present and indicated). Mechanism: reduces kidney inflammation/leak. Risks: weight gain, mood changes, infection risk. (Use only if clearly indicated by nephrology.) PMC
Anticoagulation/antiplatelet therapy (specialist-guided only) if thrombosis occurs or risk is high. Agents: LMWH, warfarin, or aspirin depending on situation. Risks: bleeding—hematology must supervise. RPTH Journal
Vitamin D (drug-grade) for bone health if low. Mechanism: improves calcium handling. Risks: excess calcium if overdosed—monitor labs. PMC
Bisphosphonates in severe pediatric osteoporosis (specialist decision). Mechanism: reduces bone resorption. Risks: fever post-infusion, bone pain. PMC
Proton-pump inhibitor if severe reflux affects feeding or meds. Mechanism: lowers stomach acid. Risks: diarrhea, low magnesium with long use. MedlinePlus
Antispasmodics for spasticity (e.g., baclofen). Mechanism: GABA-B agonist reduces muscle tone. Risks: sedation, weakness. MedlinePlus
Acetazolamide (only if a neurologist finds PMM2-like cerebellar syndrome—not standard for ALG12). Note: helpful reports are for other CDG, not proven for ALG12. Frontiers
Vaccines (drug biologics) per immunology plan; sometimes extra doses or timing changes when IgG is low. Risks: usual vaccine reactions; live vaccines need specialist review. Frontiers
Iron therapy if iron-deficiency anemia is present. Mechanism: supports red-cell production. Risks: constipation, dark stools. MedlinePlus
Pain medicines (acetaminophen/ibuprofen if safe) for musculoskeletal pain; avoid NSAIDs if kidney issues. Risks: stomach/kidney effects for NSAIDs. MedlinePlus
Anti-reflux prokinetics (specialist-guided) to improve feeding tolerance when needed. Risks: drug-specific; monitor. MedlinePlus
Important context: Nutritional sugars that help other CDG types (e.g., mannose for MPI-CDG, galactose for PGM1-CDG) do not have evidence for ALG12-CDG at this time; care remains supportive. PMC+1
Dietary “Molecular” Supplements (supportive; discuss with your team)
High-calorie formula or modular calories to reach growth targets and support immunity. MedlinePlus
Protein optimization to maintain muscle and healing (renal status considered). MedlinePlus
Vitamin D3 and calcium for bone health if low. PMC
Omega-3 fatty acids for general anti-inflammatory support (food-first when possible).
Riboflavin (B2) and thiamine (B1) – common mitochondrial-support vitamins sometimes used in neuro-metabolic care (evidence in ALG12 is limited). PMC
Carnitine if low, to support energy use (check levels first). PMC
Coenzyme Q10 for cellular energy (anecdotal in CDG; monitor response). PMC
Magnesium if low (helps muscle and nerve function).
Zinc if deficient (supports immunity and growth).
Fiber and hydration to ease constipation and improve feeding tolerance.
(These are supportive; none “cure” ALG12-CDG.) PMC
Immunity booster / Regenerative / Stem-cell” Drugs
IVIG/SCIG – the only well-accepted immune replacement when IgG is low and infections are frequent. See dosing above. Frontiers
Targeted monoclonal prophylaxis (e.g., RSV prevention in infants at risk) may be considered on a case-by-case basis by specialists.
Growth factors (e.g., G-CSF) – only if a child truly has neutropenia; not routine in ALG12-CDG. Hematologist must decide.
Erythropoietin – for significant anemia if indicated; not disease-modifying.
Hematopoietic stem-cell transplant (HSCT) – not standard for ALG12-CDG; may be discussed only in research or exceptional immune-defect settings; risks are high. PMC
Gene therapy – research stage across CDG; none approved for ALG12-CDG yet. PMC
Surgeries/Procedures
Gastrostomy tube – for severe feeding failure or unsafe swallowing; improves nutrition and lowers aspiration risk. MedlinePlus
Spinal surgery – for progressive scoliosis/kyphosis when bracing fails; improves sitting, breathing mechanics, and care. NCBI
Orchiopexy – for undescended testes in boys to protect fertility and lower torsion risk. MedlinePlus
Cochlear implant – in severe sensorineural hearing loss to improve sound access. fcdgc.rarediseasesnetwork.org
Cardiac procedures (e.g., device therapy; rarely transplant) – for advanced cardiomyopathy in expert centers. PMC
Prevention Tips
Prompt infection care; low threshold to see a clinician. Frontiers
Vaccination plan with immunology input if IgG is low. Frontiers
Nutrition and hydration to support growth and immunity. MedlinePlus
Spine monitoring (scheduled checks) to catch curves early. NCBI
Clot prevention around lines/surgeries (line care, mobilization, hydration). CDG UK
Bone health (weight-bearing activity and vitamin D as needed). PMC
Seizure plan (rescue meds, fever control, sleep routine). MedlinePlus
Cardiac follow-up if any heart signs. PMC
Dental and oral care to reduce infection sources. MedlinePlus
Genetic counseling for family planning and carrier testing. cdghub.com
When to See a Doctor (red flags)
Any fever, cough, ear pain, or chest signs in a child with low IgG. MedlinePlus
New seizures, prolonged seizures, or behavior change. MedlinePlus
Sudden swelling, severe headache, unusual bruising, or limb pain (possible clot/bleed). RPTH Journal
Breathing trouble, poor feeding, vomiting, or dehydration. MedlinePlus
Back curve that is getting worse, new weakness, or loss of skills. NCBI
Any heart symptoms (fast breathing at rest, sweating with feeds, fainting). PMC
What to Eat & What to Avoid
What to eat:
Regular balanced meals with enough calories and protein to support growth.
Iron-rich foods (meat, beans, leafy greens) if iron is low.
Dairy or fortified alternatives for calcium and vitamin D (or supplements if prescribed).
Fruits, vegetables, and fiber to help constipation.
Adequate fluids to prevent dehydration and support circulation. MedlinePlus+1
What to avoid or limit:
Long fasting (worsens low energy).
Excess salt if heart failure or edema is present. PMC
Unnecessary NSAIDs if kidney or clotting problems exist (ask your team). RPTH Journal
Unproven supplements that claim to “cure” CDG; discuss all products with your team first. PMC
FAQs
Is ALG12-CDG the same as CDG-Ig?
Yes—CDG-Ig is the older name; today it is ALG12-CDG. cdghub.comHow common is it?
Very rare. Exact numbers are unknown because many cases are missed.How is it inherited?
Autosomal recessive—parents are usually healthy carriers; each pregnancy has a 25% chance to be affected. cdghub.comWhat is the main problem in the body?
A broken step in N-linked glycosylation—the ALG12 enzyme cannot add the eighth mannose. NCBIWhy are infections common?
Because IgG antibodies can be low. Some children need immunoglobulin replacement. MedlinePlus+1What does the “type I transferrin pattern” mean?
It is a blood test hint that points to a CDG problem early in the sugar-building pathway. FrontiersIs there a cure?
No single cure yet. Care is supportive and preventive. Research is ongoing. cdghub.comDo special sugars help?
Treatments like mannose or galactose help other CDGs (MPI-CDG, PGM1-CDG), not ALG12-CDG at present. PMC+1Can my child go to school?
Yes, with supports (IEP, therapies, hearing/vision aids). Many children learn and progress.What about sports?
Light to moderate activity is encouraged, based on tone, balance, heart, and spine status.Is surgery ever needed?
Sometimes—for feeding tubes, spine correction, orchiopexy, cochlear implants, or advanced heart care. NCBI+2MedlinePlus+2How are clotting problems handled?
With careful hematology input, blood tests, and sometimes anticoagulation if clots occur. RPTH JournalWhat does brain MRI show?
Often cerebellar hypoplasia or related changes. PMCWhat is the outlook?
It varies widely. Some children are severely affected, while others have mild features and live into adulthood. fcdgc.rarediseasesnetwork.orgShould our family get genetic counseling?
Yes, for carrier testing and future pregnancy options. cdghub.com
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: September 12, 2025.
