A condition, known commonly as "black urine disease" or Alkaptonuria is a rare genetic disorder involving protein metabolism, and it has its root in the mutation of the homogentisate 1,2-dioxygenase gene, which in turn causes homogentisic acid accumulation in the body. The appearance of dark urine after exposure to air is due to this kind of accumulation; however, a variety of symptoms can be expected, such as joint stiffness, changes in pigmentation, and other long-term health complications. Although the prevalence has been estimated to be between 1 in 250,000 and 1 in 1 million people in the United States, its effects are indeed high on those affected.

Alkaptonuria is an autosomal recessive disease, meaning that the child must inherit a defective copy of the HGD gene from both parents. If both parents are carriers, their offspring have a 25% chance of inheriting two faulty genes and developing alkaptonuria. The condition is genetic but is often not diagnosed for years because it progresses slowly and its early symptoms appear to be harmless.

Symptoms of Alkaptonuria

The most characteristic and common initial symptom of alkaptonuria is dark urine. The reason for this is due to the fact that excess HGA is excreted in the urine and upon oxidation in the presence of air, it gives the urine a brown or black color. Though it is often considered cosmetic, the long-term accumulation of HGA within the connective tissues produces more complicated health problems.

Progressive joint pain and stiffness: The accumulation of HGA in cartilage leads to early-onset osteoarthritis, making movement increasingly difficult over time.

Skin and eye pigmentation changes: Affected individuals may develop bluish or grayish discoloration of the sclera (white part of the eye) and the skin, particularly in areas exposed to friction.

Cardiovascular and respiratory problems: With age, HGA accumulation can lead to valve calcifications in the heart and stiffening of connective tissues in the respiratory tract, which can cause problems in middle and old age.

Decreased mobility and spinal problems: The spine may become stiff and painful due to chronic cartilage degeneration.

These symptoms usually begin to manifest during adulthood, leading to severe complications in a person's 40s or 50s and significantly affecting the quality of their life.

How is Alkaptonuria Diagnosed?

Because of its rarity, alkaptonuria is often mistaken or overlooked early in life. However, there are several ways to confirm the condition:

Urine Testing: The gold standard in the diagnosis is the testing of urine samples for high levels of homogentisic acid via gas chromatography. In case of oxidation, which changes the color of urine to black, it is indicative of alkaptonuria.

Genetic Testing: Confirmatory genetic testing reveals mutations of the HGD gene to diagnose the condition conclusively.

Blood Tests: High levels of HGA in the blood can be used as further evidence.

Imaging Studies: X-rays and MRIs will expose cartilage and joint damage characteristic of alkaptonuria.

Management of Alkaptonuria: Is There A Cure?

At present, there is no cure for alkaptonuria; however, various treatment approaches can reduce its symptoms and slow the disease's progress:

Nitisinone Therapy: Nitisinone is a drug that inhibits the production of HGA. It has been shown to reduce HGA levels and slow tissue damage. However, it needs to be taken under close medical supervision because of potential side effects.

Low-Protein Diet: Since HGA is a byproduct of protein metabolism, reducing protein intake—especially foods rich in tyrosine and phenylalanine—may help decrease HGA production.

Pain Management: OTC pain relievers and anti-inflammatory medications can be used to relieve joint pain and stiffness.

Physical Therapy: Exercise regularly, as it may improve mobility and strengthen muscles, thus reducing strain on affected joints.

Surgical Interventions: Most people with alkaptonuria develop severe osteoarthritis necessitating joint replacement in their old age. Also, some may require heart valve replacement surgery if cardiovascular complications develop.

Life with Alkaptonuria

Although alkaptonuria is not fatal, it severely affects the quality of life. The progressive deterioration of the joints and associated symptoms can make everyday activities difficult, requiring lifestyle changes and medical interventions. The disease may cause premature aging of the joints, requiring walking aids and mobility assistance earlier than expected.

Ongoing research will continue to work on improving the treatment options by focusing on gene therapy and alternative enzyme replacement therapies. However, because of its rarity, the clinical trials and research remain sparse.

As genetic research advances, more hope for better management and possible curative approaches for alkaptonuria exists. Scientists are searching extensively for enzyme replacement therapies and innovative drugs that can target the root cause of the disorder. Being aware and being diagnosed early helps individuals better their condition and ultimately have better long-term health outcomes.

Alkaptonuria is a striking example of how one gene mutation can have widespread effects on the body. Though still a rare and often misunderstood condition, growing awareness and advances in treatment are paving the way for better care. If you or a loved one suspect symptoms of alkaptonuria, it is essential to seek early diagnosis and medical guidance to manage the disease effectively and preserve quality of life.

One of the most common contributing factors in lung cancer is smoking but a recent report suggests an alarming pattern in which cases among non-smokers are on the rise.

Pope Leo XIV was recently diagnosed with lung adenocarcinoma, a type of aggressive cancer that develops in the cells lining the lungs. He had no history of smoking. The 71-year-old pontiff underwent surgery to have part of his right lung lobe removed. According to reports, he is out of the hospital and recovering well.

Another case is of Stanford physician Bryant Lin whose stubborn cough led him to seek medical attention. After six weeks, he underwent an X-ray. The diagnosis stated that he had stage 4 lung cancer. Lin was less than a month away from turning 50, and he had never smoked a cigarette in his entire life.

“Definitely a shock,” Lin recalled according to The Washington Post. By the time doctors identified the cancer in spring 2024, it had spread to his liver, bones and brain.

According to the US Centers for Disease Control and Prevention (CDC), around 10% to 20% of lung cancers in the United States are reported in people who have never smoked or have smoked fewer than 100 cigarettes in their lifetime. That amounts to an estimated 20,000 to 40,000 cases annually.

For these patients, their no-smoking history can delay diagnosis and treatment. Hence, researchers are now looking into how environmental exposures, genetic causes and the biology of tumours may contribute to lung cancer in non-smokers.

Lung Cancer In People Who Have Never Smoked

Also read: Pope Leo XIV, Diagnosed With Lung Cancer, Undergoes Surgery As His Brother Battles Relapsed Multiple Myeloma

Smoking remains the leading risk factor for lung cancer. But other reasons like exposure to radon, secondhand smoke, air pollution and asbestos can also increase risk. Family history plays a role, especially when a first-degree relative has cancer before age 50.

Researchers are also examining genetic differences that may help explain why some people develop lung cancer despite never smoking.

A study published in September identified a rare genetic mutation concentrated in the southeastern United States that was associated with a 60-fold higher risk of lung cancer among non-smokers. The finding focuses on a possible role for inherited susceptibility, but it does not explain most cases in this group.

Lung cancer also has a different demographic profile among people who have never smoked. Women who have never smoked are more than twice as likely as their male counterparts to develop lung cancer.

“Two-thirds of nonsmoking-related lung cancer happens in women, so there’s certainly an association with female sex,” said Jaclyn LoPiccolo, a medical oncologist at Dana-Farber Cancer Institute who co-authored the mutation study.

She added, “Nonsmoking-related lung cancer is also more common in people of East Asian descent, but whether that’s a genetic or environmental association, we don’t yet know.”

These Cancers Are Often Diagnosed Late

Also read: Pope Leo XIV Resumes Daily Activities After Lung Cancer Surgery: How Recovery Looks Like After Lung Lobe Removal

People who have never smoked may not recognise a persistent cough or other respiratory symptoms as signs of lung cancer. Doctors may initially consider more common explanations if the patient has no smoking history.

Never-smokers are often diagnosed late at more advanced stages of the disease because their doctors initially consider lung cancer to be less likely.

Haiying Cheng, a medical oncologist at Montefiore Einstein Medical Center in New York, said the stigma surrounding the disease can compound the problem. “A cancer diagnosis should never become a judgment about a patient,” Cheng said.

She added that clinicians need to consider assumptions beyond smoking when it comes to lung cancer and focus on the patient’s risk profile and tumour biology.

Lin is receiving antibody therapy targeting a cancer-driving mutation. He had a positive response to treatment.

“The treatment has done wonders for me,” he said. “When I was a medical student or resident, I would have never thought a Stage 4 lung cancer patient could be very productive and have a high quality of life almost two-and-a-half years after diagnosis.”

In the United States, the US Preventive Services Task Force recommends annual low-dose CT screening for adults aged 50 to 80 who have a smoking history. People who have never smoked are not included in these recommendations.

As researchers dig deeper into lung cancer chances in non-smokers, there is growing interest in different screening recommendations. Taiwan, for example, has a national early-detection programme offering low-dose CT scans to non-smokers with a family history of lung cancer.

Lin has urged his own sons to consider screening at a younger age. “I’ve got two sons, and I told them, ‘When you hit 45 or even 40, think about getting screened,’” he said.

Many women in their forties come to my clinic with joint pain they have lived with for months, assuming it is part of getting older. World Arthritis Day is a good time to look at what changes in a woman's joints after 40 and why it pays to act early.

Why Does The Risk Rise After 40?

The biggest shift is hormonal. Oestrogen helps regulate inflammation and protects cartilage, bone and muscle. As levels fluctuate during perimenopause and fall after menopause, the joints lose part of that protection. A 2024 review in the journal Climacteric named this pattern the musculoskeletal syndrome of menopause, estimating that more than 70% of women experience joint or muscle symptoms during the transition and about one in four find them disabling.

Lower oestrogen also speeds up the loss of muscle and bone. When the thigh muscles weaken, the knee absorbs more shock with every step, which is one reason knee osteoarthritis becomes more common in women at this stage. Osteoarthritis, the gradual wear of the cartilage cushioning the bones, commonly affects the knees, hips, hands and spine. Old injuries, excess weight, and family history increase the risk.

Women are also two to three times more likely than men to develop rheumatoid arthritis, an autoimmune condition in which the immune system attacks the joint lining. It most often begins between the ages of 30 and 60.

Which Signs Should You Watch For?

One simple check is how long your joints stay stiff in the morning. Stiffness and pain that increases with movement is typical of osteoarthritis. Stiffness even with rest, especially with swelling in the small joints of both hands or wrists, suggests inflammatory arthritis and needs prompt assessment. Other signs include pain while climbing stairs or getting up from the floor, a grating feeling in the knee, firm bony swellings on the finger joints and tiredness out of proportion to your activity.

Not every ache after 40 is arthritis. Menopause-related pain, for instance, tends to move around the body. An examination, an X-ray, and simple blood tests can tell these conditions apart, so avoid self-diagnosis.

How Can You Protect Your Joints?

• Strength training: Muscle-strengthening exercise at least twice a week, focused on the thighs and hips, takes load off the knees.
• Low-impact activity: Walking, swimming, and cycling keep joints mobile without straining them.
• Weight: A study of adults with knee osteoarthritis found that every kilogram lost takes about four kilograms of load off the knee with each step.
• Diet: Get enough protein and calcium, and ask your doctor whether you need a vitamin D test.
• Daily habits: If your knees already hurt, limit deep squatting and long hours sitting cross-legged on the floor, wear supportive footwear, and avoid smoking.

When Should You See A Doctor?

Consult an orthopaedic specialist if joint pain or stiffness lasts beyond a few weeks or affects daily tasks. In rheumatoid arthritis, early treatment can slow the disease and prevent permanent joint damage. A suddenly hot, red, swollen joint with fever needs same-day attention, as it may signal infection.

Arthritis does not have to come with turning 40. Women who notice the early signs, keep their muscles strong, and see a doctor in time can stay active and independent well into later life.

By Dr Saurabh Bansal, Consultant Orthopaedic Surgeon, PB Health

Holding urine occasionally, such as during a long meeting or traffic jam, is generally not harmful for most healthy adults. However, repeatedly delaying urination for extended periods may affect urinary health, particularly in people who are prone to urinary tract infections (UTIs) or have existing bladder problems.

What Happens When You Hold Urine for Too Long?

When urine remains in the bladder for too long, it can become uncomfortable and may contribute to bladder overdistension. In some individuals, particularly those with underlying urinary retention or bladder dysfunction, regularly postponing urination may worsen existing problems.

While holding urine does not directly cause a UTI in every case, incomplete bladder emptying can increase the risk of infection.

Also read: Are People With CKD At Higher Risk Of Dementia And Cognitive Problems?

Why You Should Not Reduce Water Intake to Avoid Bathroom Break

People who work long hours or commute frequently should try to respond to the urge to urinate rather than routinely suppressing it.

Maintaining adequate hydration is equally important, as deliberately drinking less water to avoid bathroom breaks can lead to concentrated urine and may increase the risk of certain urinary problems like concentrated urine leading to crystallization and stone formation.

When Should You Seek Medical Advice?

If you experience persistent urgency, burning during urination, lower abdominal discomfort, difficulty passing urine or blood in the urine, seek medical advice. Developing regular bathroom habits and ensuring convenient access to washrooms can help support long-term urinary health.

It is also important to recognise when urinary symptoms may indicate a more serious problem. Inability to pass urine despite a strong urge, particularly when accompanied by severe lower abdominal pain or swelling, requires urgent medical attention.

Fever, chills or pain in the back or side alongside urinary symptoms may indicate a kidney infection and should be assessed promptly. Avoid assuming that such symptoms are simply the result of holding urine for too long.

By Dr. Vikram Kalra, Principal Director - Nephrology and Kidney Transplant, Aakash Healthcare Multi Speciality Hospital, Dwarka