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.

A new study published in The Lancet Regional Health–Southeast Asia has found that India accounts for 68% of all childhood cancer cases in the SAARC region.

While the country's large child population contributes to the high numbers, experts say underdiagnosis and incomplete cancer registration may mean the actual burden is even greater.

An international team of researchers, including from the US, India, and Canada, estimated that nearly 37,700 children aged up to 14 years were diagnosed with cancer across South Asia in 2022, with 17,700 deaths reported. India alone accounted for an estimated 25,939 cases and 12,028 deaths.

The researchers noted that because cancer registration remains incomplete, particularly in rural areas, the true number of childhood cancer cases in India could exceed 50,000 annually.

India's Large Child Population Drives Numbers

India is home to more than 380 million children, accounting for nearly 69% of the child population in the SAARC region. This naturally contributes to the country's higher share of childhood cancer cases and deaths.

However, experts emphasize that population size is only part of the explanation. Delayed diagnosis, limited access to specialized treatment, and gaps in cancer registration continue to affect both disease estimates and patient outcomes.

Leukemia Most Common Cancer

Dr. Narendra Agrawal, a leading Hematologist and Bone Marrow Transplant Physician and Senior Consultant and Unit Head of Haemato-Oncology at Rajiv Gandhi Cancer Institute & Research Centre, told HealthandMe that childhood cancer remains a major public health concern in India.

"Current estimates suggest that around 70,000–80,000 children and adolescents develop cancer each year, although the exact number remains uncertain due to expanding cancer registration systems". The most common childhood cancers in India include:

• Leukemia
• Lymphomas
• Brain tumors
• Bone tumors

What Causes Childhood Cancer?

Unlike many adult cancers, most childhood cancers do not have a clearly identifiable or preventable cause. Dr. Agrawal explained that, in most children, cancer develops because of genetic changes that occur during early development. These changes are usually not linked to lifestyle factors or inherited from parents.

Recognized Risk Factors

Although the causes of most childhood cancers remain unclear, some well-established risk factors include:

• Ionizing radiation: High-dose exposure before birth or during childhood increases the risk of leukemia and certain other cancers.
• Genetic syndromes: Conditions such as Down syndrome, Li-Fraumeni syndrome, and neurofibromatosis increase susceptibility to specific childhood cancers.
• Certain infections: Epstein–Barr virus (EBV) is associated with some lymphomas, HIV increases lymphoma risk, and chronic hepatitis B infection raises the risk of liver cancer.
• Environmental and parental exposures: Tobacco smoke, certain chemicals, pesticides, and some occupational exposures have been investigated as possible risk factors, although evidence remains inconclusive.

Challenges Beyond Disease Burden

Dr. Agrawal said India's substantial childhood cancer burden is largely driven by its population size. However, improving outcomes requires addressing several systemic challenges.

Key issues include:

• Delayed diagnosis
• Limited access to specialized pediatric oncology services in some regions
• Treatment abandonment
• Incomplete cancer registration

Marketed as a "harmless" alternative to cigarette smoking, vaping is increasingly emerging as a health concern, particularly for lung health, doctors warned ahead of World Lung Cancer Day on August 1.

Traditional cigarettes remain strongly linked to lung cancer, chronic obstructive pulmonary disease (COPD), and several other life-threatening illnesses. However, growing laboratory, animal, and population studies suggest vaping may also damage lung tissue, alter DNA, and potentially increase lung cancer risk—especially among people who both smoke and vape.

A recent study published in the peer-reviewed journal ERJ Open Research found that vaping may offer far less protection than many users believe when it comes to cardiovascular fitness, breathing efficiency, lung function, and blood vessel health in young adults.

"E-cigarettes are often advertised as a safer choice and as a way to help people quit smoking. But the evidence behind these claims is weak. We still don't fully know what long-term damage e-cigarettes can do to the lungs, including whether they can cause lung cancer," Dr. Shiba Kalyan Biswal, Head of Pulmonology at Shalby International Hospital, Gurugram, told HealthandMe.

Why E-Cigarettes May Raise Lung Cancer Risk

The vapor produced by e-cigarettes contains several harmful chemicals, including substances that can damage cells and DNA—the genetic material inside the body's cells.

Animal studies have found that mice exposed to e-cigarette vapor for about a year developed a type of lung cancer. Ingredients commonly used in e-cigarette liquids, such as propylene glycol and benzoic acid, may also irritate cells and trigger inflammation in the lungs.

"There have also been outbreaks of a serious vaping-related lung disease that has sent people to hospital with severe breathing problems. This shows that the risks of vaping can be unpredictable, especially when products are poorly regulated or contain unknown ingredients," Dr. Biswal explained.

She urged doctors to routinely ask patients about e-cigarette use, particularly those with breathing problems or those at higher risk of lung cancer.

"Since evidence suggests that e-cigarettes add to the risk for people who used to smoke, it may be worth including vaping history when deciding who needs lung cancer screening," she said.

Why Dual Users Face Even Greater Risk

According to Dr. Biswal, lung cancer risk appears to be even higher among people who use both e-cigarettes and conventional cigarettes, often referred to as "dual users."

Many smokers who turn to e-cigarettes intending to quit end up continuing to use both products rather than switching completely.

"This means they stay addicted to nicotine and may be exposed to even more harmful substances."

Lung Cancer Rising Among Young Non-Smokers

Doctors are also reporting more lung cancer cases among young people who have never smoked, particularly women.

Indoor air pollution, biomass fuel exposure, second-hand smoke, occupational hazards, and genetic susceptibility are increasingly contributing to the disease, said Dr. Akshay Budhraja, Senior Consultant and Head of Respiratory and Sleep Medicine at Aakash Healthcare.

"It's no longer just the lifelong smoker in his sixties—we are seeing younger patients, more women, and a growing number who have never touched a cigarette. Air quality, occupational exposure and genetic predisposition are all playing a bigger role than they used to, and that means our screening approach has to widen well beyond the traditional smoker profile," Dr. Budhraja said.

Experts said early detection through low-dose CT screening remains crucial for high-risk individuals. However, symptoms such as a persistent cough or breathlessness are often mistaken for pollution-related irritation or a lingering infection, leading many people to delay getting screened.

They also noted that lung cancer affects more than the lungs, with potential impacts on men's sexual health and women's reproductive health.

Lung Cancer Remains a Global Health Challenge

According to the World Health Organization (WHO), lung cancer remains one of the world's biggest public health challenges due to its high incidence and mortality. In 2024, it was the leading cause of cancer-related deaths globally, with an estimated 2.6 million new cases and 1.8 million deaths.

Lung cancer develops when abnormal cells grow uncontrollably in the lungs. Treatment depends on a person's medical history and the

stage of the disease.

The doctors stressed that avoiding tobacco remains the most effective way to reduce lung cancer risk.

"Smokers face nearly 20 times the risk of non-smokers, though the rising non-smoker caseload complicates that picture," said Dr. Budhraja. "Second-hand smoke is the third leading cause of lung cancer among non-smokers; radon gas, seeping in from soil, is the leading one, and home testing kits can catch it."

I've spent over three decades treating heart disease, and in that time, I've seen the same misunderstanding come up again and again, across different patients, different generations, different backgrounds. It's the one that delays diagnosis more than any other. Ask most people what menopause changes, and they'll talk about hot flashes, mood swings, or sleep. Ask me, and I'll tell you it changes something just as important: a woman's heart.

I believe menopause should be treated as a cardiovascular milestone, not just a reproductive one. We talk to women a great deal about bone density, hormonal symptoms, and fertility. We talk far less about what's happening quietly inside their arteries during this same period. That gap in the conversation is costing us early diagnoses. In some cases, it's costing lives.

How Estrogen Protects The Heart?

To understand why, it helps to look at what protects a woman's heart in the first place. For most of her reproductive years, estrogen acts almost like a quiet guardian in the background, keeping the endothelium — the inner lining of blood vessels — working well, and supporting the release of nitric oxide, which helps arteries stay relaxed and open. This is a big reason heart attacks are fairly uncommon in women before menopause, compared to men of a similar age.

Menopause takes that buffer away, slowly, not all at once. The shift usually starts during perimenopause, often well before periods actually stop. LDL, the harmful cholesterol, tends to rise; HDL, the protective kind, often falls. Blood pressure that used to be easy to control starts creeping higher. Arteries stiffen, insulin resistance sets in, and fat tends to shift toward the belly, carrying its own inflammatory effect on blood vessels. None of this feels dramatic on any single day. It just builds, quietly, year after year — enough that by ten to fifteen years past menopause, a woman's heart risk has often caught up to, and sometimes overtaken, a man's of the same age.

Also read: Lifestyle Genetics And Hormones: Understanding The Interplay Of Risk Factors For Ovarian Cancer

Ageing & Menopause: A Double Impact

Some argue this is simply age catching up, and that menopause gets blamed unfairly. There's truth in that — age alone stiffens arteries in everyone. But in my experience, losing estrogen compresses those changes into a much shorter stretch of time. It isn't one factor or the other; it's ageing, sped up by a hormonal shift arriving right in the middle of life.

That said, menopause alone doesn't determine a woman's future with heart disease. It sets the stage, but daily habits decide how the story plays out. Smoking, inactivity, weight around the middle, a diet heavy in processed food, unchecked blood pressure and blood sugar, chronic stress, poor sleep, and skipped check-ups all add their share. The reassuring part is that nearly everything on that list can be changed. I've watched patients shift their own trajectory with fairly ordinary steps — walking regularly, eating simply, sleeping better, getting basic tests done once a year.

Also read: Mood Swings, Anxiety & Brain Fog During Menopause? Expert Recommends Looking Beyond Hot Flashes

Heart Symptoms Women Should Never Ignore

What troubles me most in practice is how often real cardiac symptoms get mistaken for "just menopause." Chest pressure rather than sharp pain. New breathlessness during simple activity. Fatigue that doesn't lift with rest. Pain in the jaw, upper back, or between the shoulder blades instead of the classic left-arm pain. Palpitations that don't settle. A few months ago, a woman in her early fifties came to me convinced she had acidity — tightness in the chest, breathlessness on stairs, an occasional fluttering heartbeat. An angiogram showed a significant coronary blockage. "I thought heart problems were a man's disease," she told me. I hear some version of that sentence often, and it worries me every time.

My advice to patients is simple: perimenopause is the right time for an honest conversation with a doctor about the heart, not after something has gone wrong. That means a blood pressure check, a proper lipid profile, blood sugar and HbA1c testing, and a baseline ECG — with an echocardiogram, stress test, or coronary calcium score for those with added risk factors.

Menopause changes a great deal about a woman's body. Her heart is one of those things, whether she's thinking about it or not. Don't wait for a scare to start the conversation. Start it now, while there's still so much you can do.