Alkaptonuria: An example of a "fundamental disease"-A rare disease with important lessons for more common disorders

Gallagher, James A ORCID: 0000-0002-0852-279X, Dillon, Jane P ORCID: 0000-0002-7055-5664, Sireau, Nicolas, Timmis, Oliver and Ranganath, Lakshminarayan R (2016) Alkaptonuria: An example of a "fundamental disease"-A rare disease with important lessons for more common disorders. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 52. pp. 53-57.

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Abstract

"Fundamental diseases" is a term introduced by the charity Findacure to describe rare genetic disorders that are gateways to understanding common conditions and human physiology. The concept that rare diseases have important lessons for biomedical science has been recognised by some of the great figures in the history of medical research, including Harvey, Bateson and Garrod. Here we describe some of the recently discovered lessons from the study of the iconic genetic disease alkaptonuria (AKU), which have shed new light on understanding the pathogenesis of osteoarthritis. In AKU, ochronotic pigment is deposited in cartilage when collagen fibrils become susceptible to attack by homogentisic acid (HGA). When HGA binds to collagen, cartilage matrix becomes stiffened, resulting in the aberrant transmission of loading to underlying subchondral bone. Aberrant loading leads to the formation of pathophysiological structures including trabecular excrescences and high density mineralised protrusions (HDMPs). These structures initially identified in AKU have subsequently been found in more common osteoarthritis and appear to play a role in joint destruction in both diseases.

Item Type:	Article
Uncontrolled Keywords:	Fundamental disease, Rare disease, Alkaptonuria, Osteoarthritis, Exposed collagen hypothesis, High density mineralised protrusions (HDMPs), Trabecular excrescences
Depositing User:	Symplectic Admin
Date Deposited:	14 Jun 2017 06:26
Last Modified:	19 Jan 2023 07:36
DOI:	10.1016/j.semcdb.2016.02.020
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3001589