Makindo Medical Notes.com

Related Subjects: |Adrenal Physiology |Addisons Disease |Phaeochromocytoma |Cushing Syndrome |Cushing Disease |Congenital Adrenal hyperplasia |Primary hyperaldosteronism (Conn's syndrome) |ACTH |McCune Albright syndrome

Adrenal insufficiency and demyelination. Featured in a film called "Lorenzo's oil"

About

• Combination of Addisonian symptoms and demyelinating features
• Commonest form is X-linked recessive disorder

Aetiology

• Impaired ability to break down long-chain fatty acids due to a peroxisomal defect
• This leads to the accumulation of VLCFAs in the adrenal and brain
• The biochemical hallmark of X-linked adrenoleukodystrophy is the accumulation of very-long-chain fatty acids
• These are found in plasma, fibroblasts, and other cell types
• There is progressive failure of all steroid-secreting cells leading to adrenal and gonadal failure and central demyelination
• There is a defect in peroxisome which are usually responsible for beta-oxidation of very-long-chain fatty acids (VLCFA) Very Long Chain Fatty Acids

Clinical

• Normal in early childhood and infancy
• The childhood form starts at around age 4
• Impaired Vision and hearing
• Spastic paraparesis, dementia
• Death before puberty

Investigations

• Cortisol and ACTH show Addisonian features
• Plasma - elevated very long-chain fatty acids VLCFAs
• MRI shows extensive demyelination

Management

• Hormone replacement for Addisonian features see Hydrocortisone
• A combination of erucic acid and oleic acid (Lorenzo's oil) has led to normal levels of very-long-chain fatty acids
• But this has not altered the rate of neurological deterioration.
• There is evidence that bone marrow transplantation appears to be more effective if undertaken in the early stages of the disease

A few examples of Peroxisomal disorders showing Enzyme deficiency established and Gene involved

• Cerebrohepatorenal syndrome (Zellweger syndrome) Generalised peroxisomal enzyme deficiency PEX genes
• Neonatal adrenoleukodystrophy Generalised peroxisomal enzyme deficiency PEX genes
• Infantile Refsum disease Generalised peroxisomal enzyme deficiency PEX genes
• Hyperpipecolic acidaemia Generalised peroxisomal enzyme deficiency PEX genes
• X-linked adrenoleukodystrophy ALD protein ALD
• Refsum disease Phytanoyl CoA hydroxylase PHYH
• Mevalonate kinase deficiency Mevalonate kinase MK