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giant axonal neuropathy - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

giant axonal neuropathy

MONDO:0000128

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Overview

A rare inherited disorder affecting the neurofilaments. It is caused by mutations in the GAN gene. It is characterized by the presence of abnormally large nerve cell axons. Signs and symptoms include difficulty walking, sensory disturbances, lack of motor coordination and abnormal reflexes in the limbs.

TreatmentsNo approved treatments · 1 in pipeline

Clinical Trials2 registered · 1 recruiting

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

GeneReviews

Clinical Guidance

GAN-related neurodegeneration, caused by biallelic GAN pathogenic variants, encompasses a phenotypic continuum ranging from classic giant axonal neuropathy (GAN) – a neurodegenerative disorder affecting both the peripheral and central nervous systems at the severe end – to milder phenotypes with early-onset peripheral motor and sensory neuropathy with or without other findings. These phenotypes do not necessarily run true in families; in one family, phenotypes in family members with the same biallelic GAN pathogenic variants ranged from classic giant axonal neuropathy to milder peripheral neuropathy presentations . To date, approximately 50 families have been identified with biallelic GAN pathogenic variants [, , , , , , , , , ].

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

No consensus clinical diagnostic criteria for GAN-related neurodegeneration have been published.

Suggestive Findings

GAN-related neurodegeneration should be suspected in individuals with the following clinical, electrophysiologic, and brain imaging findings, and family history.

Clinical findings

Source: GeneReviews — "GAN-Related Neurodegeneration"

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for giant axonal neuropathy. An additional 1 compound holds orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for giant axonal neuropathy, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for giant axonal neuropathy. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Surveillance is individualized and involves monitoring response to ongoing interventions and identifying new manifestations. Surveillance may involve some or all of the recommendations in .

Table 6.

Recommended Surveillance at Each Visit for Individuals with GAN-Related Neurodegeneration

System/Concern | Evaluation

Development /

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

2 clinical trials registered, 1 recruiting. Interventions under study include gene therapy. Pipeline includes 2 PHASE1. Research is primarily sponsored by academic and government institutions.

19 publications have been identified in PubMed for giant axonal neuropathy. Research spans Basic Science / Preclinical (42%), Review / Meta-Analysis (16%), and Case Report / Case Series (16%).

Research Type	Count	% of Total
Laboratory research	8	42%

Data assembled from 5 of 12 sources · Last updated Sep 19, 2026, 6:44 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

Questions for Your Care Team

→Are any of the 2 active clinical trials a good fit for my situation?
→What is the current development status of self-complimentary adeno-associated virus vector, serotype 9, packaging the full lenght GAN gene in the viral capsid, and when might it become available?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

GeneReviews

Differential Diagnosis

Hereditary Disorders in the Differential Diagnosis of Classic Giant Axonal Neuropathy At onset, classic giant axonal neuropathy (GAN) presents with features (e.g., neuropathic deficits, giant axons, and neurofilament aggregation) similar to those associated with several severe, early-onset hereditary motor and sensory neuropathies . These neuropathies and other disorders of interest in the differential diagnosis of classic GAN are summarized in . Table 3. Genes of Interest in the Differential Diagnosis of Classic Giant Axonal Neuropathy

Gene	DiffDx Disorder	MOI	Features of DiffDx Disorder
Late-infantile metachromatic leukodystrophy (MLD) (See Arylsulfatase A Deficiency.)1	AR	Age at onset: 30 mos; typically presents w/weakness, hypotonia, clumsiness, frequent falls, toe walking, dysarthria; later signs incl spasticity, pain, seizures, compromised vision hearing. Final stage is assoc w/tonic spasms, decerebrate posturing, general unawareness of surroundings.	Progressive CNS demyelination; no hair abnormalities ATP7A
Classic Menkes disease (See ATP7A Copper Transport Disorders.)	XL	Prominent CNS involvement hair changes similar to GAN. Infants appear healthy until age 2-3 mos, when loss of developmental milestones, hypotonia, seizures, failure to thrive, concomitant characteristic hair changes (short, sparse, coarse, twisted, often lightly pigmented) occur.	Hypopigmentation of the hair; wormian bones, metaphyseal spurring of long bones, rib fractures DCAF8
Severe early-onset HMSN2,3,4	AD	Cardiomyopathy	No hair abnormalities; no prominent CNS involvement
EGR2	Severe early-onset HMSN (See CMT Overview.)	AR	Severe congenital hypomyelinating neuropathy
GDAP1	Severe early-onset HMSN (See CMT Overview.)	AR	Peripheral neuropathy typically affecting lower extremities earlier more severely than upper extremities; onset from infancy to early childhood. Neuropathy is demyelinating or axonal; vocal cord paresis is common. NEFL
Severe early-onset HMSN4 (See CMT Overview.)	ADAR	PLA2G6	—
Classic infantile neuroaxonal dystrophy (INAD)	AR	Infantile-onset disease of CNS PNS w/neurologic symptoms resembling GAN. Characteristic pathologic feature: axonal spheroids made of vesiculotubular structures (tubular membranous material w/clefts) in both CNS PNS (incl the cutaneous or conjunctival nerve twigs)	No hair abnormalities
SBF2	Severe early-onset HMSN (See CMT Overview.)	AR	Myelin outfoldings seen on nerve biopsy
SH3TC2	Severe early-onset HMSN2,4 (See SH3TC2-HMSN.)	AR	Demyelinating neuropathy; early-onset severe spine deformities.

Source: GeneReviews — "GAN-Related Neurodegeneration"

Kisho

giant axonal neuropathy

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Management Guidelines

Evaluations Following Initial Diagnosis

Therapies Under Investigation

Clinical Trials

Neurologic

Motor disability ADL

Language delay

Feeding

Optic atrophy

Recent Publications

Latest News & Developments

Compound Heterozygous COA7 Variants Presenting With Childhood-Onset Axonal Neuropathy in 2 Siblings.

giant axonal neuropathy

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Management Guidelines

Evaluations Following Initial Diagnosis

Therapies Under Investigation

Clinical Trials

Neurologic

Motor disability ADL

Language delay

Feeding

Optic atrophy

Recent Publications

Latest News & Developments

Compound Heterozygous COA7 Variants Presenting With Childhood-Onset Axonal Neuropathy in 2 Siblings.