ALKAPTONURIA

By: Angel May C. Balonkita

BMLS-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

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
Gene

Carrier
Mother

Normal
Gene

Does not have

the condition.

Carrier
Father

Altered
Gene
Normal
Gene

Carrier of the
condition.

Carrier of the
condition.

Has 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

 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.

SYMPTOM
S:

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

 Darkening of the ear

Arthritis (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:

PHENYLALANIN
E

Phenylalanine
hydroxylase

TYROSINE

Tyrosine aminotransferase
4-HYDROXYPHENYLPYRUVIC
ACID

4Hydroxyphenylpyruvi
c acid dioxygenase
Homogentisate 1,2dioxygenase

HOMOGENTISIC
ACID
MALEYLACETOACETIC
ACID

ALKAPTONURI
A

TREATMENT:
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