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PubMed This is a summary of 21 peer-reviewed journal articles Updated
Genetics

How CDG Affects the Body: Signs and Symptoms

At a Glance

Congenital disorder of glycosylation (CDG) is a highly variable, multisystem genetic disorder. Early signs in infancy often include low muscle tone, failure to thrive, neurological issues like seizures, and unique physical features such as inverted nipples or abnormal fat pads.

Because glycosylation (the process of adding sugar chains to proteins) happens in almost every cell, a defect in that process can affect many different parts of the body at the same time [1][2]. This is why CDG is called a multisystem disorder.

It is important to remember that no two children with CDG are exactly alike. Even siblings with the same genetic mutation may have different symptoms or varying levels of severity [3][4]. Your child may have many of the symptoms listed below, or they may only have a few.

Early “Red Flags” in Infancy

Many parents first notice something is different in the first few months of life. These early signs are often the clues that lead doctors to test for CDG:

  • Hypotonia: Often called “floppy baby syndrome,” this is a state of low muscle tone where an infant feels limp when held [5][6].
  • Failure to Thrive (FTT): This is when a baby has difficulty gaining weight or growing at the expected rate, despite adequate feeding [7][8].
  • Unique Physical Features: Some types of CDG, particularly PMM2-CDG, may present with specific physical markers like inverted nipples (nipples that point inward) or abnormal fat pads (unusual pockets of fat, often on the buttocks or thighs) [9].
  • Neurological Signs: Seizures, which can sometimes be difficult to control with standard medications, and developmental delays are very common early indicators [5][8].

Symptoms by Body System

Neurological (Brain and Nerves)

The nervous system is the most commonly affected system in CDG [5].

  • Ataxia: Difficulty with balance and coordination, often becoming more noticeable as a child learns to sit or walk [10].
  • Cerebellar Atrophy: A shrinking of the cerebellum, the part of the brain that controls movement and balance, which can be seen on an MRI [3][11].
  • Stroke-like Episodes (SLE): These are sudden, temporary events where a child may experience weakness on one side, confusion, or loss of consciousness. They are often triggered by a fever or a minor head injury and are NOT caused by a blood clot like a typical stroke [10][12].

Gastrointestinal (GI) and Hepatic (Liver)

  • Hepatopathy: This refers to liver disease. In many children, it shows up as elevated liver enzymes in blood tests, or an enlarged liver (hepatomegaly) [1][13].
  • Chronic Diarrhea: Some subtypes, like MPI-CDG, primarily affect the gut, causing severe diarrhea and protein loss [14][15].

Cardiac (Heart)

About 6% of children with CDG have heart involvement [16].

  • Cardiomyopathy: A condition where the heart muscle becomes thickened or weakened, making it harder to pump blood [16][17].
  • Pericardial Effusion: An accumulation of fluid in the sac surrounding the heart. If this fluid builds up quickly, it can be life-threatening and requires immediate medical attention [16][18].

Other Systems

  • Endocrine: Children may have issues with hormone regulation, such as hyperinsulinemic hypoglycemia (low blood sugar caused by too much insulin) [19][13].
  • Coagulation (Blood Clotting): CDG can affect the proteins that help blood clot. This can lead to an increased risk of either bleeding too easily or developing dangerous blood clots [20][12].

Why Is It So Variable?

The “severity” of CDG depends on how much the specific genetic mutation disrupts the glycosylation process. Some mutations allow the body to do some “work-around” glycosylation, while others block the process more completely. Because glycosylation is so fundamental, even small changes in a child’s environment (like a viral infection) can temporarily shift how their body manages, leading to a “flare” of symptoms [12][21].

To learn more about how doctors identify the specific type, proceed to Diagnostic Testing.

Common questions in this guide

What are the first signs of CDG in a baby?
Early red flags for CDG in infancy often include low muscle tone (hypotonia), difficulty gaining weight, and developmental delays. Some babies also present with unique physical features like inverted nipples or abnormal fat pads.
Can symptoms of CDG vary between siblings?
Yes, no two children with CDG are exactly alike. Even siblings who have the exact same genetic mutation can experience completely different symptoms or varying levels of severity.
Are stroke-like episodes in CDG caused by blood clots?
No, stroke-like episodes in children with CDG are not caused by blood clots like a typical stroke. These are sudden, temporary events involving weakness or confusion that are usually triggered by a fever, illness, or minor head injury.
Does CDG cause heart problems?
About 6% of children with CDG experience heart issues. This can include cardiomyopathy, which affects how well the heart pumps, or pericardial effusion, which is a dangerous buildup of fluid around the heart.
Can low muscle tone from CDG improve with therapy?
Low muscle tone, or hypotonia, is a common neurological symptom of CDG that can make a child feel limp. While it is a part of the condition, physical and occupational therapies can be used to help support muscle development and improve mobility over time.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my child's specific subtype, which body systems are most likely to be affected, and what screening schedule do you recommend?
  2. 2.My child has low muscle tone—is this a permanent part of their condition, or can it improve with therapy?
  3. 3.What should I do if my child experiences a 'stroke-like episode' or sudden weakness, and who should I contact in an emergency?
  4. 4.Are there specific physical markers, like fat pads or inverted nipples, that we should continue to monitor for changes?
  5. 5.Does my child have an increased risk for clotting or bleeding issues, and how will that affect future surgeries or treatments?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (21)
  1. 1

    Complex Phenotypes in Inborn Errors of Metabolism: Overlapping Presentations in Congenital Disorders of Glycosylation and Mitochondrial Disorders.

    Gardeitchik T, Wyckmans J, Morava E

    Pediatric clinics of North America 2018; (65(2)):375-388 doi:10.1016/j.pcl.2017.11.012.

    PMID: 29502919
  2. 2

    Hyperkinetic movement disorders: expanding the phenotype of congenital disorders of glycosylation.

    Pandey S, Chouksey A

    European journal of neurology 2019; (26(9)):1141-1142 doi:10.1111/ene.14013.

    PMID: 31206957
  3. 3

    Neurodevelopmental profiles of 14 individuals with phosphomannomutase deficiency (PMM2-CDG).

    Weixel T, Adedipe D, Muldoon G, et al.

    Journal of inherited metabolic disease 2025; (48(1)):e12782 doi:10.1002/jimd.12782.

    PMID: 39105373
  4. 4

    Multiorgan involvement and genetic spectrum of 20 Chinese patients with PMM2-CDG.

    Zhang H, Zhang J, Ma W, et al.

    Molecular genetics and metabolism 2025; (145(4)):109178 doi:10.1016/j.ymgme.2025.109178.

    PMID: 40555085
  5. 5

    Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community.

    Granjo P, Pascoal C, Gallego D, et al.

    Orphanet journal of rare diseases 2024; (19(1)):407 doi:10.1186/s13023-024-03389-2.

    PMID: 39482754
  6. 6

    Mosaicism of the UDP-Galactose transporter SLC35A2 in a female causing a congenital disorder of glycosylation: a case report.

    Westenfield K, Sarafoglou K, Speltz LC, et al.

    BMC medical genetics 2018; (19(1)):100 doi:10.1186/s12881-018-0617-6.

    PMID: 29907092
  7. 7

    DPAGT1-CDG: Recurrent fetal death.

    Tao H, Sun Y, Zhai J, Wu J

    Birth defects research 2023; (115(13)):1185-1191 doi:10.1002/bdr2.2219.

    PMID: 37421173
  8. 8

    Further Delineation of the ALG9-CDG Phenotype.

    AlSubhi S, AlHashem A, AlAzami A, et al.

    JIMD reports 2016; (27()):107-12 doi:10.1007/8904_2015_504.

    PMID: 26453364
  9. 9

    [Clinical and genetic analysis for two children with congenital disturbance of glycosylation with PMM2 gene mutations].

    Ren C, Fang F, Huang Y, et al.

    Zhonghua er ke za zhi = Chinese journal of pediatrics 2015; (53(12)):938-42.

    PMID: 26887550
  10. 10

    Stroke-Like Episodes in PMM2-CDG: When the Lack of Other Evidence Is the Only Evidence.

    Serrano M

    Frontiers in pediatrics 2021; (9()):717864 doi:10.3389/fped.2021.717864.

    PMID: 34708008
  11. 11

    Instrumented assessment of gait disturbance in PMM2-CDG adults: a feasibility analysis.

    Cirnigliaro L, Pettinato F, Valle MS, et al.

    Orphanet journal of rare diseases 2024; (19(1)):39 doi:10.1186/s13023-024-03027-x.

    PMID: 38308356
  12. 12

    Association between acute complications in PMM2-CDG patients and haemostasis anomalies: Data from a multicentric study and suggestions for acute management.

    Wicker C, Roux CJ, Goujon L, et al.

    Molecular genetics and metabolism 2023; (140(3)):107674 doi:10.1016/j.ymgme.2023.107674.

    PMID: 37542768
  13. 13

    An overlooked case of a treatable hyperinsulinemic hypoglycemia: congenital glycosylation defect Type Ib.

    Haznedar P, Eminoğlu FT

    Turk pediatri arsivi 2020; (55(1)):79-81 doi:10.5152/TurkPediatriArs.2018.18004.

    PMID: 32231455
  14. 14

    Mannose phosphate isomerase gene mutation leads to a congenital disorder of glycosylation: A rare case report and literature review.

    Lu S, Liang S, Wu Y, et al.

    Frontiers in pediatrics 2023; (11()):1150367 doi:10.3389/fped.2023.1150367.

    PMID: 37124179
  15. 15

    Mannose phosphate isomerase-congenital disorder of glycosylation leads to asymptomatic hypoglycemia.

    Luo C, Peng D, Li Y, et al.

    Molecular genetics and metabolism reports 2024; (41()):101162 doi:10.1016/j.ymgmr.2024.101162.

    PMID: 40206417
  16. 16

    Cardiomyopathy, an uncommon phenotype of congenital disorders of glycosylation: Recommendations for baseline screening and follow-up evaluation.

    Zemet R, Hope KD, Edmondson AC, et al.

    Molecular genetics and metabolism 2024; (142(4)):108513 doi:10.1016/j.ymgme.2024.108513.

    PMID: 38917675
  17. 17

    Clinical severity and cardiac phenotype in phosphomannomutase 2-congenital disorders of glycosylation : Insights into genetics and management recommendations.

    Holubova V, Barone R, Grunewald S, et al.

    Journal of inherited metabolic disease 2025; (48(1)):e12826 doi:10.1002/jimd.12826.

    PMID: 39633515
  18. 18

    Novel Splicing Variant in the PMM2 Gene in a Patient With PMM2-CDG Syndrome Presenting With Pericardial Effusion: A Case Report.

    Slaba K, Noskova H, Vesela P, et al.

    Frontiers in genetics 2020; (11()):561054 doi:10.3389/fgene.2020.561054.

    PMID: 33133147
  19. 19

    A novel homozygous mutation in the mannose phosphate isomerase gene causing congenital disorder of glycation and hyperinsulinemic hypoglycemia in an infant.

    Deeb A, Al Amoodi A

    Clinical case reports 2018; (6(3)):479-483 doi:10.1002/ccr3.1387.

    PMID: 29531722
  20. 20

    Coagulation abnormalities in a prospective cohort of 50 patients with PMM2-congenital disorder of glycosylation.

    De Graef D, Ligezka AN, Rezents J, et al.

    Molecular genetics and metabolism 2023; (139(2)):107606 doi:10.1016/j.ymgme.2023.107606.

    PMID: 37224763
  21. 21

    Congenital disorders of glycosylation type 1A associated with cerebral hemorrhagic infarction: illustrative case.

    Nomura Y, Morita T, Ueno K, et al.

    Journal of neurosurgery. Case lessons 2025; (9(1)).

    PMID: 39761563

This page provides informational content about the signs and symptoms of Congenital Disorder of Glycosylation (CDG). It is not a substitute for professional medical advice; always consult a pediatric specialist for evaluation and symptom management.

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