ALKAPTONURIA

ALKAPTONURIABy: Angel May C. BalonkitaBMLS-2A

What is Alkaptonuria?

Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air.

Ochronosis - a buildup of dark pigment in connective tissues such as cartilage and skin, is also characteristic of the disorder.

People with alkaptonuria typically develop arthritis, particularly in the spine and large joints, beginning in early adulthood. Other features of this condition can include heart problems, kidney stones, and prostate stones.How common is alkaptonuria?

This condition is rare, affecting 1 in 250,000 to 1 million people worldwide.

Alkaptonuria is more common in certain areas of Slovakia (where it has an incidence of about 1 in 19,000 people) and in the Dominican Republic. How do people inherit alkaptonuria?This condition is inherited in an autosomal recessive pattern.

The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Autosomal Recessive Pattern:Altered GeneAltered GeneNormal GeneNormal GeneCarrier MotherCarrier FatherDoes not have the condition.Carrier of the condition.Has the condition.Carrier of the condition.What genes are related to alkaptonuria?HGD gene.

What is the normal function of the HGD Gene?TheHGDgene provides instructions for making an enzyme called homogentisate oxidase.

This enzyme participates in a step-wise process that breaks down two protein building blocks (amino acids), phenylalanine and tyrosine, when they are no longer needed or are present in excess.

How are changes in theHGDgene related to health conditions?

More than 65 mutations in theHGDgene have been identified in people with alkaptonuria.

Mutations in theHGDgene inactivate homogentisate oxidase by changing its structure.

Without a functional version of this enzyme, phenylalanine and tyrosine are not broken down properly and homogentisic acid builds up in the body.

Excess homogentisic acid and related compounds are deposited in connective tissues such as cartilage and skin, which causes them to darken.

Over time, a buildup of this substance in the joints leads to arthritis.

Homogentisic acid is also excreted in urine.

CAUSES:Inability to convert homogentisic acid to maleylacetoacetic acid.

Homogentisic acid is subsequently converted to benzoquinone acetic acid and spontaneously polymerized.

Exogenous agents including quinacrine (Atabrine), carbolic acid, and hydroquinone have been reported to cause an ochronotic picture without the joint disease.

SYMPTOMS: Dark spots on the white of the eye (sclera) and cornea.

Darkening of the earArthritis (especially of the spine) that gets worse over time

Urine in an infants diaper may darken and can turn almost black after several hours. However, many persons with this condition may not know they have it until mid-adulthood (around age 40), when joint and other problems occur.

Alkaptonuria Metabolic Pathway:PHENYLALANINETYROSINE4-HYDROXYPHENYLPYRUVIC ACIDHOMOGENTISIC ACIDMALEYLACETOACETIC ACIDPhenylalanine hydroxylaseTyrosine aminotransferase4-Hydroxyphenylpyruvic acid dioxygenaseHomogentisate 1,2- dioxygenaseALKAPTONURIATREATMENT:

Some patients benefit from high-dose vitamin C.

EXAMS AND TESTS:A urine test (urinalysis) is done to test for alkaptonuria. If ferric chloride is added to the urine, it will turn the urine a black color in patients with this condition.Thank You for listening