Adrenoleukodystrophy
Related Subjects:
|Adrenal Physiology
|Addisons Disease
|Phaeochromocytoma
|Cushing Syndrome
|Cushing Disease
|Congenital Adrenal hyperplasia
|Primary hyperaldosteronism (Conn's syndrome)
|ACTH
|McCune Albright syndrome
🧠⚡ Adrenoleukodystrophy (ALD) = Adrenal insufficiency + demyelination.
🎬 Featured in the film “Lorenzo’s Oil.”
📖 About
- Combination of Addisonian symptoms (adrenal failure) and progressive neurological decline due to demyelination.
- Most common form = X-linked recessive disorder (boys affected; female carriers usually asymptomatic or mild).
🧬 Aetiology
- Defect in peroxisomes, which normally degrade very-long-chain fatty acids (VLCFAs).
- Accumulation of VLCFAs in adrenal cortex, brain white matter, and testes.
- Biochemical hallmark: ↑ VLCFAs in plasma, fibroblasts, and other tissues.
- Results in adrenal insufficiency, hypogonadism, and progressive demyelination.
🩺 Clinical Features
- Normal development until early childhood.
- Childhood cerebral form (age ~4–8): vision/hearing loss 👀👂, behavioural changes, spastic paraparesis 🦵, seizures, dementia.
- Progressive → wheelchair bound, loss of speech, death often before puberty.
- Addisonian features: hyperpigmentation, hypotension, electrolyte disturbances (Na ↓, K ↑).
🔎 Investigations
- Bloods: ↓ Cortisol, ↑ ACTH (primary adrenal insufficiency).
- Biochemical: ↑ VLCFAs in plasma.
- MRI brain: extensive white matter demyelination.
- Genetic testing: ABCD1 gene mutation (X-linked).
💊 Management
- Hormone replacement: hydrocortisone for adrenal insufficiency (± fludrocortisone).
- Lorenzo’s oil (erucic acid + oleic acid): ↓ plasma VLCFAs ✅, but ❌ no clear neurological benefit once disease is established.
- Bone marrow or stem cell transplant: may stabilise progression if performed very early (pre-symptomatic/MRI-only changes).
- Supportive: physiotherapy, seizure control, multidisciplinary input.
🧩 Related Peroxisomal Disorders
- Zellweger syndrome – generalised peroxisomal enzyme deficiency (PEX genes).
- Neonatal adrenoleukodystrophy – PEX genes.
- Infantile Refsum disease – PEX genes.
- Hyperpipecolic acidaemia – PEX genes.
- X-linked adrenoleukodystrophy – ABCD1 gene (ALD protein defect).
- Refsum disease – phytanoyl CoA hydroxylase deficiency (PHYH).
- Mevalonate kinase deficiency – MVK gene.
