Rare Disease Turns Joints, Urine Black

By

Published August 11, 2010

| FoxNews.com

Shane Blamires deals with quality-of-life issues daily. As a respiratory therapist, his job is to make life for people with chronic ailments as comfortable as possible. But, as an alkaptonuria patient, he struggles with managing his own disease with very few treatment options.

Blamires, a 38-year-old from Lewiston, Idaho, has black urine disease. It’s a rare, genetic condition, and fewer people have heard of it than can pronounce its clinical name – alkaptonuria.

On the other hand, its informal name, black urine disease, is self-explanatory. Just ask Blamires.

“It’s kind of gross I guess, but … it turned the urine color black. And that’s the acid; it oxidizes in the air,” he said.

Alkaptonuria (AKU) is a metabolic disorder in which patients can’t fully digest an acid called tyrosine because of an enzyme deficiency they are born with. This causes 2,000 times the normal amount of homogentistic acid (HGA) to build up. HGA is then converted into a black pigment in a process known as ochronosis that can turn tissue, muscle, cartilage, bone – and yes, even urine – black.

Beyond the shock of one’s urine turning black, which only happens when it’s left to stand, patients commonly have bluish-black discoloration in the ear and the whites of the eye, and experience joint and back pain.

“This HGA damages the body and the main issue is early severe arthritis,” said Dr. L. Ranganath, a leading expert on AKU based at the Royal Liverpool University Hospital in England, and a trustee of the AKU Society, a patient-led support network that raises awareness about the rare disease.

Blamires, a member of the AKU Society, was diagnosed in 2006 shortly after having spinal fusion surgery, during which his surgeon was shocked to find the disc he was removing was black.

“It was really dramatic. I think it just totally astounded the surgeon,” said Dr. Jeffrey Butler, a clinical rheumatologist at the University of Washington, who Blamires was referred to after the operation.

Butler diagnosed him just months later, but it was Blamires who introduced the idea that it could be AKU by researching his symptoms online.

“Shane's been a real go-getter. He's done a lot of the leg work and that's been a big help to me,” said Butler, adding that Blamires is his only patient with the rare disease.

AKU is more common in certain countries, but occurs in one in a million U.S. births, according to the EMedicine website.

Consequently, many doctors have never seen it, so it is often misdiagnosed as arthritis.

“Every doctor I go to, I have to explain to them what it is; what I’m doing about it,” said Blamires, adding that his doctors have largely taken his lead on how to treat his disease. “It’s not the best way of doing medicine, but it’s kind of the only thing that’s out there.”

Although the disease is genetic, most patients aren’t diagnosed until their 30s or 40s when the majority of symptoms – joint pain, ligament and tendon ruptures, kidney and prostate stones, leaky heart valves leading to heart failure, and kidney damage and failure – begin to show.

“The major issue for all patients is the constant back and joint pains from around age 30 onwards affecting quality of life – work, family and leisure,” Ranganath said. “Osteoarthritis-like joint damage is 100 percent certain for all patients.”

Blamires had his first joint replacement surgery of the knee in January 2009. But a little further east in Pesquin Isle, Wis., another AKU patient has had seven joint replacement surgeries before the age of 60, and one more last year at the age of 61, making it eight in total.

“It’s a cartilage degeneration disease really,” said Nick Williams, a retiree who shrunk three inches in his late 40s. “It’s like a sponge in the sink; it’s real good for a real long time, and then one day you pick up the sponge and it falls to bits in your hands. And that’s really what happens to cartilage.”

Williams has had each of his ankles, knees and hips replaced – his left hip was replaced twice because the plastic failed in the first one – in addition to his right shoulder, all in the span of 14 years.

Unlike Blamires, Williams was diagnosed when he was a baby.

“In those days, they didn’t have throwaway diapers, and when my parents first changed and washed my diaper, it ended up having a dark stain that does not come out, even with bleach,” Williams said.

His parents were worried so they brought him to the doctor. At the time, doctors didn’t know AKU was a metabolic imbalance and that the HGA in his urine is what caused the deep stain. But they were able to provide a roughly accurate diagnosis because they knew of the research done on it as early as the 1890s, which led to it becoming the first disease ever to be identified as inherited.

But if this early warning sign is missed, the disease isn’t noticeable in the years in between infancy and middle-age. Fast forward 40 years, and Williams found himself slowly losing mobility. It started with difficulty climbing stairs. Then, the disease began to spiral out of control.

At 41, he had four kidney stones in five months. Then he ruptured his right and left Achilles tendons at 42 and 44 respectively.

Joint replacement and pain medication are the only proven treatments for the floodgate of symptoms that hit many AKU patients in middle-age.

“The thing is you really don't treat alkaptonuria like it's alkaptonuria, you treat the symptoms that manifest themselves,” Williams said. “You do a joint replacement, you do a valve replacement; you do whatever is necessary, as if it were some other disease because it manifests itself like a joint failure.”

Clinical trials are being done to find a treatment that addresses the disease. The National Institutes of Health recently concluded a trial of an enzyme blocker called nitisonone to neutralize the effects of HGA. Neither Blamires nor Williams were included in the trial of 58 people with AKU, despite applying. But Blamires said he has been taking the same enzyme blocker used in the NIH study for four years.

Although the drug containing nitisonone was effective in blocking the excessive amounts of HGA in both the trial and Blamires, it would never be able to repair the damage already done.

“Once the integrity of the joint has been violated, you get this progressive problem where there's arthritis that we can't really reverse,” Butler said. “Even if you're able to block the process, the arthritis does progress.”

For Blamires, the hope is that the nitisonone drug will stop the disease’s progression before it begins to affect his heart.

Although AKU isn’t fatal, it can have a drastic effect on quality of life.

“I can still golf, which is fine by me. But a lot of other things like just doing basic yard work or things like that where there is a lot of lifting or bending, I just can’t do it anymore. And a lot of times – I have two younger girls – I can’t even pick them up,” Blamires said.

Another factor AKU patients have to deal with is the isolation felt because there is no one who knows exactly what you’re going through.

“I felt all alone when I first had it,” Blamires said. “I remember my wife just crying for nothing; nobody to talk to, nobody knew anything about it.”

That’s where organizations like the AKU Society come in.

“It was set up to raise awareness about AKU, help patients, and fund research to find a cure,” said Nick Sireau, who has two children with the disease and helped found the AKU Society in 2003, along with Ranganath and others.

Even though Williams doesn’t hold any illusions that a miracle drug will restore his youth and allow him to do cartwheels down the driveway anytime soon, he is hopeful that medicine will catch up with the world’s first-known genetic disease.

Both Ranganath and Butler share Williams’ hope, and want to see further clinical trials. But in order to prevent the effect of early osteoarthritis, Butler stresses the need to begin treating it early.

“The hope would be that if you could initiate this at a very young age before any damage or any deposition of the HGA has happened; that you might be able to prevent the arthritis from developing,” said Butler, adding that gene therapy may also have potential as a future treatment.

Click here to learn more about the AKU Society.

URL

http://www.foxnews.com/story/2010/08/11/rare-disease-turns-joints-urine-black/