ALG3-CDG

What it is

From: Orphanet

A form of congenital disorders of N-linked glycosylation characterized by severe neurological involvement, including hypotonia, developmental delay, intellectual disability, postnatal microcephaly, and progressive brain and cerebellar atrophy. Epilepsy with hypsarrythmia is frequently reported. Additional features that may be observed include failure to thrive, arthrogryposis multiplex congenita (AMC), vision impairment (optic atrophy, iris coloboma) and facial dysmorphism (hypertelorism with a broad nasal bridge, large and thick ears, thin lips, micrognathia). The disease is caused by loss of function mutations of the gene ALG3 (3q27.3).

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal cerebral morphology · Very frequent (99-80%)

Any structural abnormality of the telencephalon, which is also known as the cerebrum.

Abnormal enzyme/coenzyme activity · Obligate (100%)

Concentration or activity of an enzyme is above or below the limits of normal in the blood circulation.

Abnormality of the gastrointestinal tract · Very frequent (99-80%)

An abnormality of the gastrointestinal tract.

Feeding difficulties · Very frequent (99-80%)

Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.

Global developmental delay · Very frequent (99-80%)

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

Hypotonia · Very frequent (99-80%)

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Recurrent infections · Very frequent (99-80%)

Increased susceptibility to infections as manifested by repeated bouts of infection.

Abnormal cardiovascular system morphology · Frequent (79-30%)

Any structural anomaly of the heart and blood vessels.

Abnormal pinna morphology · Frequent (79-30%)

An abnormality of the pinna, which is also referred to as the auricle or external ear.

Abnormality of limb bone morphology · Frequent (79-30%)

Any abnormality of bones of the arms or legs.

Abnormality of the endocrine system · Frequent (79-30%)

An abnormality of the endocrine system.

Abnormality of the eye · Frequent (79-30%)

Any abnormality of the eye, including location, spacing, and intraocular abnormalities.

Abnormality of the genitourinary system · Frequent (79-30%)

The presence of any abnormality of the genitourinary system.

Abnormality of the nose · Frequent (79-30%)

An abnormality of the nose.

Other findings in the same source

From: Orphanet

Additional reported features include Abnormality of the respiratory system (Frequent (79-30%)); Decreased liver function (Frequent (79-30%)); Hearing impairment (Frequent (79-30%)); Microcephaly (Frequent (79-30%)); Osteopenia (Frequent (79-30%)); Seizure (Frequent (79-30%)); Abnormality of limbs (Frequent (79-30%)); Abnormality of blood and blood-forming tissues (Occasional (29-5%)); Brain atrophy (Occasional (29-5%)); Dystonia (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Infancy; Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 15.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing ALG3-CDG is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for ALG3-CDG. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.