Show Summary Details
Page of

Disorders of peroxisomal metabolism in adults 

Disorders of peroxisomal metabolism in adults

Chapter:
Disorders of peroxisomal metabolism in adults
Author(s):

Anthony S. Wierzbicki

DOI:
10.1093/med/9780199204854.003.1209_update_002

July 30, 2015: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

Update:

Data on biochemistry of peroxisomal enzymes and transporters updated.

Mechanism of toxicity of phytanic and pristanic acids updated.

Description of the adult presentation of acyl-coenzymeA oxidase deficiency as the cause of pseudoadrenoleukodystrophy.

Data on the pathophysiological mechanisms behind adrenoleukodystrophy updated.

Updated on 28 Nov 2013. The previous version of this content can be found here.
Page of

PRINTED FROM OXFORD MEDICINE ONLINE (www.oxfordmedicine.com). © Oxford University Press, 2015. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy).

date: 26 April 2017

The peroxisome is a specialized organelle which employs molecular oxygen in the oxidation of complex organic molecules including lipids. Enzymatic pathways for the metabolism of fatty acids, including very long-chain fatty acids (VLCFA) enable this organelle to carry out β‎-oxidation in partnership with mitochondria. A peroxisomal pathway for isoprenoid lipids derived from chlorophyll, such as phytanic acid, utilizes α‎-oxidation, but a default mechanism involving ω‎-oxidation may also metabolize phytanic acid and its derivatives.

The biochemical manifestations, molecular pathology, and diverse clinical features of many peroxisomal disorders have now been clarified, offering the promise of prompt diagnosis, better management and useful means to provide appropriate genetic counselling for affected families. At the same time, specific treatments including rigorous dietary interventions and plasmapheresis to remove undegraded toxic metabolites offer credible hope of improvement and prevention of disease in affected individuals.

Inborn errors of peroxisomal metabolism usually present in infancy and childhood, but some disorders typically become manifest later in life and in adults, in whom the progress is often slow.

Particular adult peroxisomal disorders

X-linked adrenoleukodystrophy (X-ALD)—due to mutation in the gene for an ATP-binding cassette (ABC) protein of unknown function and characterized by accumulation of unbranched saturated VLCFAs, particularly hexacosanoate (C26), in the cholesterol esters of brain white matter, adrenal cortex and certain sphingolipids of the brain. The disease has multiple phenotypes: it may present in adolescence with slowly progressive stiffness, clumsiness, weakness, weight loss, and skin pigmentation typical of Addison’s disease; it may present in adults with primarily psychiatric manifestations. Most cases develop increasing handicap; management is palliative and supportive in most instances.

Adult Refsum’s disease—due in most cases to mutation in the gene for phytanoyl CoA-hydroxylase (PhyH) such that patients are unable to detoxify phytanic acid by α‎-oxidation and have greatly elevated levels of this in their plasma. Usually presents in late childhood with progressive deterioration of night vision, the occurrence of progressive retinitis pigmentosa, and anosmia; late features include deafness, ataxia, polyneuropathy, ichthyosis and cardiac arrhythmias. Treatment is by restriction of dietary phytanic acid, with or without its elimination by plasmapheresis or apheresis.

Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription.

Please subscribe or login to access full text content.

If you have purchased a print title that contains an access token, please see the token for information about how to register your code.

For questions on access or troubleshooting, please check our FAQs, and if you can't find the answer there, please contact us.