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PubMed This is a summary of 15 peer-reviewed journal articles Updated

Long-Term Surveillance and Complications

At a Glance

Long-term care for PMM2-CDG requires proactive surveillance of the heart, liver, brain, and endocrine systems. Patients need routine testing, including clinical rating scales and specialized blood work, to catch and manage complications early. Those with the p.Val231Met variant require closer cardiac monitoring.

Living with PMM2-CDG requires a shift from the initial diagnostic phase to long-term surveillance. Because the condition affects multiple systems, “watching and waiting” is done with a specific plan to catch and manage complications early. By staying ahead of potential issues in the heart, liver, and endocrine system, you can provide the most stable environment for growth and long-term health [1][2].

Risk Stratification: The Role of the p.Val231Met Variant

Genetic testing does more than just name the condition; it helps doctors understand specific risks. One important discovery in PMM2-CDG research is the impact of the p.Val231Met variant [3].

  • Cardiac Risk: Patients who carry this specific genetic change have a significantly higher risk of cardiac involvement. This variant is associated with severe cardiac complications, such as fluid around the heart (pericardial effusion) or heart muscle weakness (cardiomyopathy), which require immediate and proactive monitoring to prevent life-threatening events [3][4].
  • Proactive Care: If this variant is present, the cardiologist will likely recommend more frequent heart checks (echocardiograms and EKGs) to ensure any changes are managed immediately [3].

Measuring Progress: NPCRS and ICARS

To track how a patient is doing over time, doctors use standardized “scoring” tools. These help move away from “gut feelings” toward objective data.

  • NPCRS (Nijmegen Pediatric CDG Rating Score): This is a comprehensive “report card” for the whole body. It looks at everything from vision and hearing to liver function and growth. It helps your team see which systems are stable and which need more support [5][6].
  • ICARS (International Cooperative Ataxia Rating Scale): This scale focuses specifically on ataxia (balance and coordination). It measures things like walking stability and hand tremors. A stable or improving ICARS score is an encouraging sign that the neurological system is adapting [7][8].

Essential Long-Term Monitoring

Organ System What to Monitor Why It Matters
Brain / Cerebellum Coordination (ICARS) and Brain MRI [8][9] Cerebellar size can change, especially in the first decade of life [9].
Liver Liver enzymes (AST/ALT) and Ultrasound [10][11] To catch signs of liver stress or scarring early [10].
Endocrine Morning Cortisol and ACTH [12][13] To screen for adrenal insufficiency (a life-threatening lack of stress hormones) [12].
Blood / Coagulation Antithrombin III and Clotting Factors [14][11] Low levels can increase the risk of blood clots or bleeding [14].

A Sample Surveillance Schedule

While every plan is personalized, a typical long-term schedule often looks like this [1][15]:

  • Every 6–12 Months: Full blood panel (liver enzymes, thyroid function, and coagulation factors like Antithrombin III) and an endocrine check for adrenal function [1][12].
  • Annually: Comprehensive clinical scoring (NPCRS/ICARS), eye exams for strabismus, and a heart check (echocardiogram), especially for those with the p.Val231Met variant [5][15][3].
  • Every 2–5 Years: Repeat brain imaging (MRI) to monitor the cerebellum, and bone density scans to check for scoliosis or bone strength [9][11].

Note: In PMM2-CDG, standard blood tests for cortisol can sometimes be misleading due to the glycosylation defect. Your endocrinologist may need to use specialized testing to get an accurate picture of adrenal health [13].

Common questions in this guide

How does the p.Val231Met variant affect PMM2-CDG?
Patients with the p.Val231Met genetic variant have a significantly higher risk of severe cardiac complications, such as fluid around the heart or heart muscle weakness. They require more frequent heart monitoring to prevent life-threatening events.
What are the NPCRS and ICARS scoring tools used for?
These standardized tools help doctors objectively track a patient's progress over time. NPCRS measures overall body function and organ health, while ICARS specifically evaluates neurological symptoms like balance, coordination, and ataxia.
How is adrenal insufficiency monitored in PMM2-CDG?
Doctors screen for adrenal insufficiency by checking morning cortisol and ACTH levels. Because standard cortisol blood tests can sometimes be misleading due to the underlying glycosylation defect, specialized endocrine testing may be necessary.
What kind of long-term monitoring is needed for the liver?
Liver health is monitored through regular blood tests for liver enzymes, such as AST and ALT, along with routine ultrasounds. This helps catch early signs of liver stress or scarring before they become severe issues.
How often should brain imaging be repeated for PMM2-CDG patients?
Brain MRIs are typically repeated every 2 to 5 years. This allows the medical team to monitor the size and health of the cerebellum, which can change significantly during the first decade of life.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Is the p.Val231Met variant present in our child's genetic report, and how does that specifically change our cardiac monitoring plan?
  2. 2.Can you provide us with our child's current NPCRS and ICARS scores to help us understand their clinical baseline?
  3. 3.Since total cortisol can be unreliable in PMM2-CDG, how will we accurately screen for adrenal insufficiency?
  4. 4.What is the long-term plan for monitoring liver health, and at what point would a liver transplant ever be discussed?
  5. 5.How often should we repeat brain imaging (MRI) to monitor for changes in the cerebellum?

Questions For You

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References

References (15)
  1. 1

    International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up.

    Altassan R, Péanne R, Jaeken J, et al.

    Journal of inherited metabolic disease 2019; (42(1)):5-28 doi:10.1002/jimd.12024.

    PMID: 30740725
  2. 2

    Patient-reported outcomes and quality of life in PMM2-CDG.

    Ligezka AN, Mohamed A, Pascoal C, et al.

    Molecular genetics and metabolism 2022; (136(2)):145-151 doi:10.1016/j.ymgme.2022.04.002.

    PMID: 35491370
  3. 3

    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
  4. 4

    Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature.

    Schiff M, Roda C, Monin ML, et al.

    Journal of medical genetics 2017; (54(12)):843-851 doi:10.1136/jmedgenet-2017-104903.

    PMID: 28954837
  5. 5

    Genotype-Phenotype Correlations in PMM2-CDG.

    Vaes L, Rymen D, Cassiman D, et al.

    Genes 2021; (12(11)) doi:10.3390/genes12111658.

    PMID: 34828263
  6. 6

    Long-term follow-up in PMM2-CDG: are we ready to start treatment trials?

    Witters P, Honzik T, Bauchart E, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2019; (21(5)):1181-1188 doi:10.1038/s41436-018-0301-4.

    PMID: 30293989
  7. 7

    Phosphomannomutase deficiency (PMM2-CDG): ataxia and cerebellar assessment.

    Serrano M, de Diego V, Muchart J, et al.

    Orphanet journal of rare diseases 2015; (10()):138 doi:10.1186/s13023-015-0358-y.

    PMID: 26502900
  8. 8

    Clinical and radiological correlates of activities of daily living in cerebellar atrophy caused by PMM2 mutations (PMM2-CDG).

    Pettinato F, Mostile G, Battini R, et al.

    Cerebellum (London, England) 2021; (20(4)):596-605 doi:10.1007/s12311-021-01242-x.

    PMID: 33619652
  9. 9

    Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG).

    de Diego V, Martínez-Monseny AF, Muchart J, et al.

    Journal of inherited metabolic disease 2017; (40(5)):709-713 doi:10.1007/s10545-017-0028-4.

    PMID: 28341975
  10. 10

    Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up.

    Starosta RT, Boyer S, Tahata S, et al.

    Orphanet journal of rare diseases 2021; (16(1)):20 doi:10.1186/s13023-020-01630-2.

    PMID: 33413482
  11. 11

    [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
  12. 12

    Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?

    Čechová A, Honzík T, Edmondson AC, et al.

    Molecular genetics and metabolism 2021; (133(4)):397-399 doi:10.1016/j.ymgme.2021.06.003.

    PMID: 34140212
  13. 13

    Suspected Central Adrenal Insufficiency in a Patient with Phosphomannomutase 2-Congenital Disorder of Glycosylation.

    Ødum SF, Grønborg SW, Main KM, Klose M

    JCEM case reports 2025; (3(11)):luaf237 doi:10.1210/jcemcr/luaf237.

    PMID: 41080975
  14. 14

    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
  15. 15

    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

This page explains long-term surveillance strategies for PMM2-CDG for educational purposes. Always consult your child's medical team to create a personalized monitoring and treatment plan.

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