Adrenomyeloneuropathy

Summary

Adrenomyeloneuropathy (MONDO:0015339) is a disease with 1 cohort gene and 15 clinical trials. Top therapeutic interventions include albumin human, vitamin e, and bezafibrate.

At a glance

• Cohort genes: 1
• Phenotypes (HPO): 49
• Clinical trials: 15

Clinical features

Signs & symptoms

Clinical features (HPO)

49 HPO clinical features (Orphanet curated; top 49 by frequency):

HPO ID	Term	Frequency
HP:0000764	Peripheral axonal degeneration	Very frequent (80-99%)
HP:0002143	Abnormality of the spinal cord	Very frequent (80-99%)
HP:0002936	Distal sensory impairment	Very frequent (80-99%)
HP:0004359	Abnormal circulating fatty-acid concentration	Very frequent (80-99%)
HP:0007199	Progressive spastic paraparesis	Very frequent (80-99%)
HP:0009053	Distal lower limb muscle weakness	Very frequent (80-99%)
HP:0030177	Abnormality of peripheral nervous system electrophysiology	Very frequent (80-99%)
HP:0031064	Impaired continence	Very frequent (80-99%)
HP:0040078	Axonal degeneration	Very frequent (80-99%)
HP:0000849	Adrenocortical abnormality	Frequent (30-79%)
HP:0001000	Abnormality of skin pigmentation	Frequent (30-79%)
HP:0001257	Spasticity	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0002064	Spastic gait	Frequent (30-79%)
HP:0002213	Fine hair	Frequent (30-79%)
HP:0002607	Bowel incontinence	Frequent (30-79%)
HP:0002839	Urinary bladder sphincter dysfunction	Frequent (30-79%)
HP:0003487	Babinski sign	Frequent (30-79%)
HP:0006827	Atrophy of the spinal cord	Frequent (30-79%)
HP:0007006	Dorsal column degeneration	Frequent (30-79%)
HP:0007266	Cerebral dysmyelination	Frequent (30-79%)
HP:0007372	Atrophy/Degeneration involving the corticospinal tracts	Frequent (30-79%)
HP:0008167	Very long chain fatty acid accumulation	Frequent (30-79%)
HP:0008969	Leg muscle stiffness	Frequent (30-79%)
HP:0009830	Peripheral neuropathy	Frequent (30-79%)
HP:0010284	Intra-oral hyperpigmentation	Frequent (30-79%)
HP:0011749	Adrenocorticotropic hormone excess	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0030014	Female sexual dysfunction	Frequent (30-79%)
HP:0031845	Abnormal libido	Frequent (30-79%)
HP:0040307	Male sexual dysfunction	Frequent (30-79%)
HP:0100291	Abnormality of central somatosensory evoked potentials	Frequent (30-79%)
HP:0100639	Erectile dysfunction	Frequent (30-79%)
HP:0100816	Lip hyperpigmentation	Frequent (30-79%)
HP:0410263	Brain imaging abnormality	Frequent (30-79%)
HP:0000012	Urinary urgency	Occasional (5-29%)
HP:0000016	Urinary retention	Occasional (5-29%)
HP:0000020	Urinary incontinence	Occasional (5-29%)
HP:0000708	Atypical behavior	Occasional (5-29%)
HP:0000846	Adrenal insufficiency	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0002292	Frontal balding	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)
HP:0003418	Back pain	Occasional (5-29%)
HP:0004302	Functional motor deficit	Occasional (5-29%)
HP:0008207	Primary adrenal insufficiency	Occasional (5-29%)
HP:0012534	Dysesthesia	Occasional (5-29%)
HP:0100502	Decreased circulating vitamin B12 concentration	Occasional (5-29%)
HP:0100543	Cognitive impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	adrenomyeloneuropathy
Mondo ID	MONDO:0015339
Orphanet	139399
ICD-10-CM	E71.522
ICD-11	1214673956
SNOMED CT	65389002
UMLS	C1527231
MedGen	315918
GARD	0010614
Is cancer (heuristic)	no

Also known as: adrenomyeloneuropathy · AMN

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › X-linked disease › adrenoleukodystrophy › adrenomyeloneuropathy

Related subtypes (2): X-linked cerebral adrenoleukodystrophy, isolated adrenal insufficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ABCD1	Supportive	X-linked	adrenomyeloneuropathy	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCD1	Orphanet:139396	X-linked cerebral adrenoleukodystrophy
ABCD1	Orphanet:139399	Adrenomyeloneuropathy
ABCD1	Orphanet:369942	CADDS
ABCD1	Orphanet:388	Hirschsprung disease

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABCD1	HGNC:61	ENSG00000101986	P33897	ATP-binding cassette sub-family D member 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCD1	ATP-binding cassette sub-family D member 1	ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCD1	Transporter	yes	7.6.2.4	ABC_transporter-like_ATP-bd, AAA+_ATPase, FA_transporter

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	1
left adrenal gland	1
left adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCD1	201	ubiquitous	marker	ileal mucosa, left adrenal gland cortex, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCD1	1,181

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCD1	P33897	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ABCD1 causes ALD	1	5710.0×	0.003	ABCD1
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	1	1903.3×	0.004	ABCD1
Linoleic acid (LA) metabolism	1	1142.0×	0.004	ABCD1
Beta-oxidation of very long chain fatty acids	1	878.5×	0.004	ABCD1
alpha-linolenic acid (ALA) metabolism	1	713.8×	0.004	ABCD1
Peroxisomal lipid metabolism	1	671.8×	0.004	ABCD1
ABC transporters in lipid homeostasis	1	601.0×	0.004	ABCD1
Class I peroxisomal membrane protein import	1	519.1×	0.004	ABCD1
ABC transporter disorders	1	439.2×	0.004	ABCD1
Protein localization	1	190.3×	0.009	ABCD1
Disorders of transmembrane transporters	1	139.3×	0.011	ABCD1
Fatty acid metabolism	1	131.3×	0.011	ABCD1
ABC-family protein mediated transport	1	121.5×	0.011	ABCD1
Metabolism of lipids	1	31.6×	0.038	ABCD1
Transport of small molecules	1	25.1×	0.045	ABCD1
Disease	1	13.1×	0.081	ABCD1
Metabolism	1	11.6×	0.086	ABCD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peroxisomal membrane transport	1	8426.0×	1e-03	ABCD1
very long-chain fatty-acyl-CoA catabolic process	1	8426.0×	1e-03	ABCD1
positive regulation of unsaturated fatty acid biosynthetic process	1	5617.3×	1e-03	ABCD1
sterol homeostasis	1	4213.0×	1e-03	ABCD1
long-chain fatty acid import into peroxisome	1	3370.4×	1e-03	ABCD1
regulation of fatty acid beta-oxidation	1	2808.7×	1e-03	ABCD1
long-chain fatty acid catabolic process	1	2808.7×	1e-03	ABCD1
myelin maintenance	1	2808.7×	1e-03	ABCD1
regulation of mitochondrial depolarization	1	2808.7×	1e-03	ABCD1
fatty acid elongation	1	2407.4×	1e-03	ABCD1
very long-chain fatty acid catabolic process	1	2407.4×	1e-03	ABCD1
positive regulation of fatty acid beta-oxidation	1	1532.0×	0.001	ABCD1
fatty acid derivative biosynthetic process	1	1532.0×	0.001	ABCD1
regulation of cellular response to oxidative stress	1	1296.3×	0.001	ABCD1
regulation of oxidative phosphorylation	1	1203.7×	0.001	ABCD1
neuron projection maintenance	1	1123.5×	0.001	ABCD1
negative regulation of reactive oxygen species biosynthetic process	1	991.3×	0.002	ABCD1
fatty acid homeostasis	1	936.2×	0.002	ABCD1
alpha-linolenic acid metabolic process	1	887.0×	0.002	ABCD1
peroxisome organization	1	802.5×	0.002	ABCD1
very long-chain fatty acid metabolic process	1	766.0×	0.002	ABCD1
linoleic acid metabolic process	1	702.2×	0.002	ABCD1
unsaturated fatty acid biosynthetic process	1	648.1×	0.002	ABCD1
long-chain fatty acid biosynthetic process	1	443.5×	0.002	ABCD1
negative regulation of cytokine production involved in inflammatory response	1	421.3×	0.002	ABCD1
fatty acid beta-oxidation	1	374.5×	0.003	ABCD1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABCD1	7.6.2.4	ABC-type fatty-acyl-CoA transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ABCD1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ABCD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 15.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE2	3
PHASE2/PHASE3	2
PHASE3	1
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00545597	PHASE3	TERMINATED	A Phase III Trial of Lorenzo’s Oil in Adrenomyeloneuropathy
NCT02961803	PHASE2/PHASE3	COMPLETED	MD1003-AMN MD1003 in Adrenomyeloneuropathy
NCT04303416	PHASE2/PHASE3	COMPLETED	Plasma Exchange With Albumin in AMN Patients
NCT01495260	PHASE2	COMPLETED	A Clinical Trial for AMN: Validation of Biomarkers of Oxidative Stress, Efficacy and Safety of a Mixture of Antioxidants
NCT03864523	PHASE2	COMPLETED	Effect of Pioglitazone Administered to Patients With Adrenomyeloneuropathy
NCT05146284	PHASE2	WITHDRAWN	Study to Assess PXL770 in Subjects With Adrenomyeloneuropathy (AMN) Form of X-linked Adrenoleukodystrophy (X-ALD or ALD)
NCT05394064	PHASE1/PHASE2	TERMINATED	A Study to Evaluate Administration of SBT101 Gene Therapy in Adult Patients With Adrenomyeloneuropathy (AMN)
NCT01787578	PHASE1	WITHDRAWN	Safety and Pharmacodynamic Study of Sobetirome in X-Linked Adrenoleukodystrophy (X-ALD)
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT04925349	Not specified	RECRUITING	Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia
NCT05443906	Not specified	RECRUITING	Home Exercise for Individuals with Neurodegenerative Disease
NCT01165060	Not specified	COMPLETED	The Effect of Bezafibrate on the Level of Very Long Chain Fatty Acids (VLCFA) in X-linked Adrenoleukodystrophy (X-ALD)
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT05008874	Not specified	TERMINATED	Study of Disease Progression in Adults With Inherited Forms of Spastic Paraplegia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALBUMIN HUMAN	4	1
VITAMIN E	4	1
BEZAFIBRATE	3	1
LIPOIC ACID, ALPHA	3	1
SOBETIROME	2	1
CHEMBL3739769	0	1
ALPHA-TOCOPHEROL	0	1
THIOCTIC ACID	0	1