ALG9-CDG

What it is

From: Orphanet

A rare form of congenital disorders of N-linked glycosylation characterized by progressive microcephaly, hypotonia, developmental delay, drug-resistant infantile epilepsy, and hepatomegaly. Additional features that may be observed include failure to thrive, pericardial effusion, renal cysts, skeletal dysplasia, facial dysmorphism (frontal bossing, hypertelorism, depressed nasal bridge, low-seated ears, large mouth) and hydrops fetalis. The disease is caused by loss-of-function mutations in the gene ALG9 (11q23).

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.

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.

Intellectual disability · Very frequent (99-80%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Seizure · Very frequent (99-80%)

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

Abnormal heart morphology · Frequent (79-30%)

Any structural anomaly of the heart.

Hepatomegaly · Frequent (79-30%)

Abnormally increased size of the liver.

Hypotonia · Frequent (79-30%)

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.

Inverted nipples · Frequent (79-30%)

The presence of nipples that instead of pointing outward are retracted inwards.

Pericardial effusion · Frequent (79-30%)

Accumulation of fluid within the pericardium.

Progressive microcephaly · Frequent (79-30%)

Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.

Skeletal dysplasia · Frequent (79-30%)

A general term describing features characterized by abnormal development of bones and connective tissues.

Abnormal bone ossification · Occasional (29-5%)

Any anomaly in the formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone or a bony substance.

Abnormal left ventricular outflow tract morphology · Occasional (29-5%)

An abnormality of the outflow tract of the left ventricle.

Abnormal lung lobation · Occasional (29-5%)

A developmental defect in the formation of pulmonary lobes.

Abnormal renal artery morphology · Occasional (29-5%)

Any structural abnormality of the renal artery.

Other findings in the same source

From: Orphanet

Additional reported features include Aplasia cutis congenita of scalp (Occasional (29-5%)); Asthma (Occasional (29-5%)); Atrial septal defect (Occasional (29-5%)); Bicornuate uterus (Occasional (29-5%)); Bifid uvula (Occasional (29-5%)); Brachycephaly (Occasional (29-5%)); Broad ischia (Occasional (29-5%)); Cerebellar atrophy (Occasional (29-5%)); Cerebral atrophy (Occasional (29-5%)); Convex nasal ridge (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Antenatal; Infancy; Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 12.0; 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 ALG9-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 ALG9-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.