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# Congenital disorder of glycosylation type Ia (PMM2-CDG)

The most common congenital disorder of glycosylation: proteins lack sugar chains, causing low tone, a small [cerebellum](https://durgical.com/en/anatomy/anterior-quadrangular-lobule/) and problems in many organs.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Cerebellum](https://durgical.com/en/anatomy/anterior-quadrangular-lobule/)
- [Vermis](https://durgical.com/en/anatomy/central-lobule/)
- [Liver](https://durgical.com/en/anatomy/liver/)
- [Pericardium](https://durgical.com/en/anatomy/pericardium/)

## In biochemistry

- [Glycoproteins and protein glycosylation (N- and O-linked)](https://durgical.com/en/biochemistry/topics/glycoproteins-and-protein-glycosylation/)

## What it is

An inherited defect of phosphomannomutase 2 (gene PMM2) that impairs N-linked glycosylation of proteins; it is the most frequent of the congenital disorders of glycosylation (CDG).

## Who gets it

More than 800 affected people have been described worldwide; it is the most common CDG. Its frequency in Colombia is not known.

## Causes

- Autosomal recessive variants in PMM2

## Risk factors

- Carrier parents
- Affected sibling

## Pathophysiology

PMM2 converts mannose 6-phosphate into mannose 1-phosphate, the precursor of GDP-mannose. Without enough GDP-mannose, the dolichol-linked oligosaccharide is not built properly and many proteins are under-glycosylated. Poorly glycosylated proteins fold badly, are degraded or work abnormally: clotting factors and anticoagulant proteins, hormones, transport proteins (transferrin) and brain proteins. The cerebellum is especially affected.

## Classification

- Infantile multisystem form: hypotonia, failure to thrive, liver, heart and kidney involvement
- Late-infantile and childhood ataxia–intellectual disability form
- Adult stable disability form

## Symptoms and signs

- Weak muscle tone and poor feeding in infancy
- Inverted nipples and abnormal fat pads on the buttocks
- Crossed eyes (strabismus) and abnormal eye movements
- Developmental delay, ataxia and later intellectual disability
- Stroke-like episodes and seizures

## Red flags

- Infant with failure to thrive, hypotonia and fluid around the heart
- Bleeding or clotting problems in a child with developmental delay

## Diagnosis

**Clinical**
Infant with hypotonia, inverted nipples, abnormal fat distribution, strabismus and cerebellar signs.

**Tests**
Serum transferrin isoelectric focusing (type 1 pattern), [liver](https://durgical.com/en/anatomy/liver/) enzymes, clotting factors (low factor XI, antithrombin, protein C and S), thyroid tests; PMM2 enzyme activity and gene testing confirm it.

**Imaging**
Brain MRI with cerebellar hypoplasia or atrophy; echocardiography for pericardial effusion or cardiomyopathy.

## Treatment

**Rehabilitation**
Physiotherapy, occupational and speech therapy for motor and language delay

**Medical**
Treatment of seizures, thyroid dysfunction and clotting problems as they appear

**Follow-up**
Regular monitoring of liver, heart, [kidneys](https://durgical.com/en/anatomy/kidney/), eyes and coagulation

**Conservative**
Nutritional support for feeding problems (thickened feeds or tube feeding when needed)

## Complications

- Death in the first years in about a fifth of severely affected infants
- Thrombosis or bleeding
- Retinitis pigmentosa and progressive skeletal deformity

## Prognosis

Severe infantile forms carry high early mortality; those who survive infancy often reach adulthood with stable disability.

## Test yourself

Think of the answer, then tap the question to see it.

## Which reaction does PMM2 catalyse?

Mannose 6-phosphate → mannose 1-phosphate, needed to make GDP-mannose for N-glycan synthesis.

## Which screening test suggests a congenital disorder of glycosylation?

Isoelectric focusing of serum transferrin, which shows under-sialylated forms.

## What are two typical physical findings of PMM2-CDG in infants?

Inverted nipples and abnormal fat pads, along with strabismus and hypotonia.

## Why do patients have clotting abnormalities?

Clotting factors and natural anticoagulants (antithrombin, proteins C and S) are glycoproteins that are made poorly without proper glycosylation.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/conditions/congenital-disorder-of-glycosylation-type-ia/)

## Related conditions

- [I-cell disease (mucolipidosis II)](https://durgical.com/en/conditions/i-cell-disease/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [PMM2-congenital disorder of glycosylation: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/pmm2-congenital-disorder-of-glycosylation/) (MedlinePlus, US National Library of Medicine, 2026); [PMM2 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/pmm2/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Source: https://durgical.com/en/conditions/congenital-disorder-of-glycosylation-type-ia/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/congenital-disorder-of-glycosylation-type-ia/