Pediatrics

Recognizing the Signs: Symptoms of PMM2-CDG Across Ages

At a Glance

PMM2-CDG is a highly variable condition with symptoms that evolve as a child grows. Infants often present with low muscle tone, abnormal fat pads, and feeding difficulties. In childhood, symptoms typically shift to developmental delays, cerebellar ataxia, and stroke-like episodes.

PMM2-CDG is a multisystemic condition, meaning it affects many different parts of the body at once ^[1]. However, the way it looks can change significantly over a person’s life. While every journey is different, doctors have identified “hallmark” signs that often appear during infancy and others that become more noticeable in childhood and adolescence ^[2]^[3].

Hallmark Signs in Infancy

In the first year of life, PMM2-CDG often presents with unique physical features and developmental challenges. These signs can be “clues” that help specialists reach a diagnosis.

Distinctive Physical Features: Many infants with PMM2-CDG have inverted nipples (nipples that point inward instead of outward) and abnormal fat pads ^[3]. These fat pads are typically found on the buttocks or the outside of the thighs and may have a “pitted” or unusual texture ^[4].
Central Hypotonia: This is often described as “floppy baby syndrome.” It refers to low muscle tone in the trunk and neck, making it difficult for the baby to hold their head up or sit without support ^[5]^[6].
Failure to Thrive: Many infants struggle to gain weight or grow at the expected rate despite adequate feeding ^[1]. To ensure they receive the nutrition they need to grow, doctors often recommend a feeding tube (such as a G-tube), which is a very common and supportive step for many CDG families ^[2].
Strabismus (Esotropia): This is a condition where the eyes do not align properly; specifically, one or both eyes may turn inward toward the nose ^[3].
Liver and Blood Findings: Even if a baby looks healthy, blood tests may show elevated liver transaminases (enzymes that leak when the liver is stressed) and low levels of certain clotting factors, like Antithrombin III ^[3]^[7].

Symptoms in Childhood and Adolescence

As children move out of infancy, the focus often shifts toward neurological and coordination challenges.

Cerebellar Ataxia: The cerebellum is the part of the brain that controls balance and fine motor skills. In PMM2-CDG, the cerebellum may be smaller than usual (cerebellar atrophy) ^[8]. This leads to ataxia, which causes “drunken-like” walking, shakiness, or difficulty with tasks like buttoning a shirt ^[9]^[10].
Intellectual Disability: Most children experience some degree of developmental delay or intellectual disability ^[1]. This can range widely; some children attend mainstream schools with support, while others require more intensive assistance ^[11].
Stroke-Like Episodes (SLEs): These are sudden events that look like a stroke—such as temporary weakness on one side of the body or confusion—but are not caused by a typical blood clot in the brain ^[12]. They are often triggered by a fever or a minor head injury ^[13].
Skeletal Changes: Some older children may develop scoliosis (curvature of the spine) or other bone-related changes as they grow ^[3].

A Key Difference: The Role of Seizures

One of the most important ways PMM2-CDG differs from other types of Congenital Disorders of Glycosylation (CDG) is the timing of seizures. In many other CDGs, seizures are a primary symptom at birth or in early infancy ^[5].

In PMM2-CDG, seizures typically do not happen at the start ^[5]. While they can develop later in childhood or adolescence, they are often manageable and respond well to standard medications like levetiracetam ^[14]. If a newborn is having frequent seizures, doctors will often look at other CDG types before confirming PMM2-CDG.

Variability is the Rule

It is vital to remember that PMM2-CDG is heterogeneous, meaning the severity varies widely from one individual to the next ^[15]. Some individuals may have very mild symptoms and may not be diagnosed until they are 8 years old or even older, while others may face more significant health challenges from birth ^[16]^[11]. Your care team will focus on specific symptoms to create a personalized support plan.

Common questions in this guide

What are the early physical signs of PMM2-CDG in babies?

Many infants with PMM2-CDG present with inverted nipples, abnormal 'pitted' fat pads on the buttocks or thighs, and central hypotonia, often referred to as 'floppy baby syndrome.'

Why do babies with PMM2-CDG often need a feeding tube?

Infants with PMM2-CDG frequently experience failure to thrive, struggling to gain weight despite adequate feeding. A feeding tube, such as a G-tube, is a common supportive measure to ensure they receive the necessary nutrition to grow.

What is a stroke-like episode in PMM2-CDG?

A stroke-like episode is a sudden event causing temporary weakness or confusion that mimics a stroke but is not caused by a blood clot. In children with PMM2-CDG, these episodes are often triggered by a fever or a minor head injury.

Does PMM2-CDG cause seizures?

While seizures are not typically present at birth in PMM2-CDG, they can develop later in childhood or adolescence. When they do occur, they generally respond well to standard anti-seizure medications.

How does PMM2-CDG affect a child's balance and movement?

The condition can cause the cerebellum to be smaller than usual, leading to cerebellar ataxia. This results in shakiness, unsteady walking, and difficulty with fine motor skills like buttoning a shirt.

Curated prompts to bring to your next appointment.

1.Does my child currently have physical signs like inverted nipples or fat pads that help confirm the PMM2-CDG diagnosis?
2.Based on my child's age, what should we be watching for in terms of cerebellar ataxia or balance issues?
3.How should we monitor my child's liver and blood clotting factors (like Antithrombin III) over time?
4.What is the risk of stroke-like episodes, and what specific emergency protocol should we follow if one occurs?
5.Since seizures don't usually happen at onset in PMM2-CDG, what are the early warning signs we should look for as our child grows?

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

References (16)

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2
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Altassan R, Péanne R, Jaeken J, et al.
Journal of inherited metabolic disease 2019; (42(1)):5-28 doi:10.1002/jimd.12024.
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3
[Clinical and genetic analysis for two children with congenital disturbance of glycosylation with PMM2 gene mutations].
Ren C, Fang F, Huang Y, et al.
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PMID: 26887550
4
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PMID: 29654385
5
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6
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PMID: 35154715
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Coagulation abnormalities in a prospective cohort of 50 patients with PMM2-congenital disorder of glycosylation.
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PMID: 37224763
8
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Cerebellum (London, England) 2021; (20(4)):596-605 doi:10.1007/s12311-021-01242-x.
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9
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de Diego V, Martínez-Monseny AF, Muchart J, et al.
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10
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.
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11
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Vals MA, Morava E, Teeäär K, et al.
American journal of medical genetics. Part A 2017; (173(6)):1620-1624 doi:10.1002/ajmg.a.38235.
PMID: 28425223
12
Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy.
Izquierdo-Serra M, Martínez-Monseny AF, López L, et al.
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13
Association between acute complications in PMM2-CDG patients and haemostasis anomalies: Data from a multicentric study and suggestions for acute management.
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14
Neurological manifestations in PMM2-congenital disorders of glycosylation (PMM2-CDG): Insights into clinico-radiological characteristics, recommendations for follow-up, and future directions.
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16
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This page describes the potential symptoms of PMM2-CDG for educational purposes only. Because the condition varies widely from child to child, always consult your pediatric neurologist or care team for personalized medical advice and symptom management.

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