Alkaptonurie (AKU) community

Alkaptonurie (AKU) ist eine seltene autosomal-rezessive Erbkrankheit des Tyrosinstoffwechsels. Patienten haben eine 2000-fache höhere Anreicherung des Zwischenproduktes Homogentisinsäure, was einen Knorpelabbau mit Symptomen ähnlich einer früh einsetzenden Arthrose verursacht.

« Back to the Articles list

Orphanet article on AKU (2007)

Written by Prof. B. Porfirio , published 10 months ago.

Summary

Alkaptonuria is characterised by the accumulation of homogentisic acid (HGA) and its oxidised product benzoquinone acetic acid (BQA), leading to a darkening of the urine when it is left exposed to air, grey-blue colouration of the eye sclerae and the ear helix (ochronosis), and a disabling joint disease involving both the axial and peripheral joints (ochronotic arthropathy).
Prevalence is estimated at 1-9/1 000 000. Many affected individuals are asymptomatic and unaware of their condition until adulthood; however, homogentisic aciduria may be recognised early in infancy (dark-stained diapers). Unusual pigmentation of the skin overlying cartilage throughout the body can be observed after the third decade. Muscular-skeletal symptoms begin in the third decade with back pain and stiffness: involvement of the large peripheral joints usually occurs several years after spinal changes, often leading to end-stage joint disease requiring surgical replacement. Ochronotic peripheral arthropathy is generally degenerative in nature but joint inflammation can be observed in some cases. Joint mobility is diminished. Ankylosis may be present.
Signs of aortic or mitral valvulitis may be present. Alkaptonuria, inherited as an autosomal recessive trait, involves a block of the phenylalanine and tyrosine catabolic pathway. Patients are homozygous or compound heterozygous for mutations in the HGD (homogentisate 1,2-dioxygenase) gene. More than 70 different point mutations have been described worldwide, interfering with the complex hexameric structure of the HGD enzyme. Tissue damage results from the presence of BQA, which tends to polymerise to a melanin-like pigment with a high affinity for connective tissue.
This pigment is able to trigger numerous redox reactions and induce free radical production, causing further damage to the connective tissue. Although unproven, it is assumed that the polymer accumulation also causes an inflammatory response resulting in calcium deposition in affected joints. Homogentisic acid can be identified in urine using gas chromatography-mass spectroscopy. As many patients present without dark urine, it may be advisable to look for homogentisate in all patients with radiographic evidence of osteoarthritis. A spinal x-ray will reveal disk degeneration combined with dense calcification, particularly in the lumbar area. Acute intermittent porphyria (which may cause dark urine), can be ruled out by the presence of homogentisate, whereas rheumatoid arthritis, osteoarthritis or ankylosing spondylitis can be excluded by radiographs. Family members should be referred for genetic counselling. Medical therapy may slow the rate of pigment deposition. This should minimise articular and cardiovascular complications in later life.
Unfortunately, there are no preventive or curative measures for the disease to date. Dietary restriction is beneficial, but compliance is often limited. Therapeutic strategies focusing on perturbing the altered phenylalanine-tyrosine pathway have been devised (e.g. , nitisinone). However, the long-term effectiveness and safety of this drug have yet to be established. Other possible approaches are aimed at exploring the effects of antioxidant biomolecules in preventing the conversion of HGA to the polymeric material deposited in the cartilaginous tissues (e.g., N-acetylcysteine).
However, previous attempts with vitamin C have been proved to be largely unsatisfactory. Older individuals may require removal and fusion of lumbar discs. Hip or knee joint replacement may be necessary. Life expectancy is not significantly reduced but progressive functional decline is observed with a loss of mobility.

*Author: Prof. B. Porfirio (January 2007)*.

Article online here: http://bit.ly/eabhJs

Written by Prof. B. Porfirio , published 10 months ago.

No comment for «Orphanet article on AKU (2007)»

Expand all ]

No comment yet.

Leave a comment

You must be registered and signed in to leave a comment. Sign in now.

Patient groups

  • AKU Society UK

  • Alcaptonurie France

  • findAKUre

  • L’aim AKU

  • AKU Society of North America

Alkaptonuria (AKU) Recent Activity

  • -

    5th International Workshop on AKU
    topic, published 13 days ago

    show transcript

    A selection of presentations from those speakers who have given permission for their slideshows to be published are now available to download on the AKU Society website at:

    http://www.alkaptonuria.info/557296

    Thanks Oliver from the AKU Society

  • -

    LETTRE D’INFORMATION N° 14 (SEPTEMBRE 2011)
    document, published 3 months ago

    show transcript

    Cette lettre est diffusée par courrier postal ou internet aux personnes atteintes d’Alcaptonurie-Ochronose, à leurs familles, aux amis et aux membres de l’ALCAP, aux donateurs, aux médecins et chercheurs, et à toute personne qui s’intéresse à l’Alcaptonurie en France, en Belgique et en Suisse.

  • -

    Update
    topic, published 3 months ago

    show transcript

    After these summer months, with a moody weather season and my health being as variable as the weather, here I am back to you taking a little time to write.

    You certainly know that the AKU Society is organizing the 5th International Workshop on AKU This event will be held at the Medical Institu...

  • -

    Action shot photo competition of EULAR for world arthritis day
    topic, published 3 months ago

    show transcript

    Dear all,
    I just submitted an 'action shot photo’ to enter a competition of
    the European Arthritis Foundation (EULAR) specially designed for the
    world arthritis day. The slogan for this competition is move to
    improve, i.e. how sport can improve mobility or slow down the
    progress of one’s ...

  • -

    AKU Society's Year in Review
    topic, published 5 months ago

    show transcript

    Check it out here:
    http://www.alkaptonuria.info/557292

    While on the website, don't forget to book for the upcoming November meeting in Liverpool:

    http://www.alkaptonuria.info/557296

  • -

    Getting information on AKU...
    topic, published 5 months ago

    show transcript

    The National Institutes of Health have Genetic and Rare Disease (GARD) Information specialists that may be able to help you find information.

    The GARD Information Center does not provide genetic counseling and does not offer diagnostic testing, referrals, medical treatment or advice.

    Ther...

  • -

    AKU
    topic, published 5 months ago

    show transcript

    I am 67 yrs old and I feel like I'm 107 The pain in my joints are unbearable almost all the time. I was diagoinsed with this when I was about 50's or so. The pain just keeps on getting worse and it is so hard to get around. I walk with a cane ,out of the house.In the house I walk with a walker. I...

  • -

    Nitisinone (NTBC) In Different Age Groups Of Patients With Alkaptonuria
    news, published 5 months ago

    show transcript


    The objective of this research is to explore reported age related differences in toxicity of nitisinone and its pharmacokinetic underpinnings and to develop an optimal therapeutic requirement for a targeted population of presymptomatic patients...

  • -

    Collagen atomic scale molecular disorder in ochronotic cartilage from an alkaptonuria patient, ob...
    news, published 5 months ago

    show transcript


    In pilot studies of the usefulness of solid state nuclear magnetic resonance spectroscopy in characterizing chemical and molecular structural effects of alkaptonuria on connective tissue, we have obtained (13) C spectra from articular cartilage...

  • -

    An update on molecular genetics of Alkaptonuria (AKU)
    news, published 6 months ago

    show transcript


    Alkaptonuria (AKU) is an autosomal recessive disorder caused by a deficiency of homogentisate 1,2 dioxygenase (HGD) and characterized by homogentisic aciduria, ochronosis, and ochronotic arthritis. The defect is caused by mutations in...