A 35 year Old Man Presents With A Long History Of Backpain

A 35 year Old man is seen in The Physician office for a prolonged history of back pain. The patient says the back pain started about 12 years back and is progressively getting worse. The pain is disabling him and he cannot participate in any kind of sports which he is very interested to take part. He takes ibuprofen for the pain which he now feels is not helping. For the past two years he has also noticed intermittent pain and swelling in both of his knee joints.
On examination of the locomotor system there was pain and loss of lumbar lordosis. His knee joints were swollen, with bilateral effusion.
On general Physical examination, he was noticed to have bluish discoloration of his ear cartilage. The picture is shown below:

He was advised some lab work to be done that also included a routine urine analysis. The lab technician forgot his specimen on the table for a few hours and when returned observed a color change shown below.

The physician was noticed about the color change of the urine and he ordered to test urine homogentisic acid levels which came out elevated.

What is the Diagnosis?
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Alkaptonuria.

Case Discussion:
Alkaptonuria is an inherited (autosomal reccessive) rare genetic disorder that is caused by a mutation that leads to defective synthesis of the enzyme homogentisate oxidase. This enzyme normally helps in the breakdown of amino acids phenylalanine and tyrosine, which are an important building blocks of protein.
The result of this defect is an accumulation of a substance homogentisic acid in the blood and the tissues. Homogentisic acid and its oxidated form alkapton are excreted in urine which gives urine its unusually dark color when left standing for sometime. The accumulating homogentisic acid also causes damage to the cartilage causing osteoarthrits and joint pains.

Clinical features:
Patients are usually asymptomatic at young age but gradually develop symptoms of pain in weight bearing joints of spine, hips and knees. With time the pain may become severe enough to interfere with daily activities. Some patients may be accidentally diagnosed by looking at dark color of urine when left for sometime. In some patients slate blue or grey discoloration may be seen in the sclera or the ear cartilage.

Diagnosis: is confirmed by finding homogentisic acid in the urine.

Treatment: There is no specific treatment for alkaptonuria. Large doses of vitamin C may help in slowing down the accumulation of the pigment in the cartilage. Patients are advised to take a low protein diet to reduce amino acid levels and there metabolism. Some patients may need early joint replacement surgeries.

Prognosis: Life expectancy of patients with alkaptonuria is fairly normal but the problems arise due to complications of arthritis, heart valve abnormalities and kidney stones.