Alkaptonuria is a rare genetic disorder.

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. This blue-black
pigmentation usually appears after age 30.

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.

The discovery of the gene responsible for alkaptonuria and a

number of genes responsible for human inborn errors of
metabolism, have exploited
 Symptoms of alkaptonuria

Normal urine Urine from patients

with alkaptonuria

Patients may display painless bluish darkening of the outer ears,

nose and whites of the eyes. Longer term arthritis often occurs.
Homogentisic acid is an intermediate in the degradation pathway of
phenylalanine. The reaction is catalysed by homogentisate dioxygenase
(HGO).
homogentisic acid
OH

O O

HOOC C C
CH CH CH2 CH2 COOH
OH

HGO maleylacetoacetic acid

CH2

COOH

A deficiency of HGO causes

alkaptonuria
 Catabolic pathway for phenylalanine and
tyrosine

Defect here causes Homogentisate

dioxygenase
alkaptonuria

Defect here causes Fumarylacetoacetate

Type I Tyrosinemia hydrolase
 Mutations in the HGD gene cause
alkaptonuria.
• The HGD gene provides instructions for making an enzyme called
homogentisate oxidase.

• This enzyme helps break down the amino acids phenylalanine and
tyrosine, which are important building blocks of proteins.

• Mutations in the HGD gene impair the enzyme's role in this process.
As a result, a substance called homogentisic acid, which is produced as
phenylalanine and tyrosine are broken down, accumulates in the body.

• Excess homogentisic acid and related compounds are deposited in

connective tissues, which causes cartilage and skin to darken.

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

Homogentisic acid is also excreted in urine, making the urine turn dark
when exposed to air.
Tyrosinemia is diagnosed by a blood and urine test.
Tyrosinemia is treated by a low protein diet (low in
phenylalanine, methionine and tyrosine) and a drug
called NTCB.

WHAT ARE THE SYMPTOMS OF TYROSINEMIA?

The clinical features of the disease ten to fall into two
categories, acute and chronic.

In the so-called acute form of the disease, abnormalities

appear in the first month of life. Babies may show poor weight
gain, an enlarged liver and spleen, a distended abdomen,
swelling of the legs, and an increased tendency to bleeding,
particularly nose bleeds.

Jaundice may or may not be prominent. Despite vigorous

therapy, death from hepatic failure frequently occurs between
three and nine months of age unless a liver transplantation is
performed.