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.

August 18 marks World Breast Cancer Research Day, a day that reminds us that every major breakthrough in cancer care has its roots in research. The medicines that are prescribed, the diagnostic technologies that we use, the targeted therapies that we offer and our growing understanding of why cancers develop and spread, are all outcomes of regular scientific research.

India carries one of the world's largest cancer burdens. According to IARC's GLOBOCAN 2022 estimates, India recorded approximately 1.41 million new cancer cases and more than 916,000 cancer deaths in 2022. Breast cancer alone was the leading cancer among Indian women and also the leading cancer overall.

India as a country, has a large and diverse patient population, significant clinical expertise, strong medical institutions and a pharmaceutical industry with enormous manufacturing capabilities. But there is a crucial gap between manufacturing what the world has already discovered and researching newer medical opportunities.

A significant proportion of cutting-edge cancer research continues to emerge from countries with substantially larger and more established research ecosystems. When scientific discoveries, new molecules, diagnostic technologies or treatment approaches are developed elsewhere, Indian patients benefit from them at a later stage.

We Need To Move Beyond A Few Centres Of Excellence

We have limited institutes that have made important contributions to cancer care and research. But considering India's population and cancer burden, the scale of research infrastructure needs to expand substantially. We need more dedicated cancer-research institutes, stronger university hospital industry collaborations, modern laboratories, biobanks, genomic databases, data-science capabilities and trained physician-scientists.

Cancer is not just one disease. It comprises of multiple biological subtypes, and the way a tumour behaves can vary significantly between individuals and populations. Therefore, India needs research that focusses specifically towards Indian patients.

Also read: Groundbreaking Experimental Vaccine May Prevent Pancreatic Cancer From Spreading, Early Trial Finds

Clinical Trials Can Be Part Of The Solution

India has a formal Clinical Trials Registry, and the registry currently records more than 100,000 trials across areas of medicine.

For eligible patients, participation in an appropriate clinical trial may provide access to an investigational therapy or treatment strategy that is not yet routinely available. Clinical trials generate evidence that can improve future treatment for thousands or millions of patients.

Also read: UK Set To Implement Stricter Protocol For Prostate Cancer Testing; Who Is Eligible To Get Tested?

Research Needs To Become A Policy Priority

We need to create an ecosystem that moves from discovery to translation to patient care. That means incentivizing research institutions and researchers, supporting young physician-scientists, strengthening public-private partnerships and making it easier for promising discoveries to move from laboratories into clinical development.

We need to have an ecosystem, where healthcare research, particularly research addressing diseases with an enormous Indian burden should receive a much greater and more targeted share of national research investment. A large, diverse population can generate valuable real-world evidence. Large patient cohorts can help researchers understand disease patterns. Indian genetic and molecular data can help answer questions that may not be adequately addressed through studies conducted in other countries.

From Manufacturing Medicines To Discovering The Next Generation Of Treatments

India has already demonstrated that it can serve the world as a pharmaceutical manufacturing powerhouse. We should look at also becoming the research hub for the world by combining our pharmaceutical manufacturing strength, clinical expertise, technology capabilities and patient population.

The opportunity is already in front of us.

What we need now is the policy ambition to implement it.

By Dr. Kapil Goyal, Consultant – Medical Oncology, Rajiv Gandhi Cancer Institute & Research Centre (RGCIRC)

If you believe having a healthy body mass index (BMI) means you have a low risk of heart disease, you may be wrong. A new study suggests that abdominal fat may predict cardiovascular disease risk better than BMI alone.

The study, published in the Journal of the American College of Cardiology (JACC), found that failing to account for waist circumference (WC) or waist-to-hip ratio (WHR) may lead to misclassification of cardiovascular disease risk.

“Indeed, it appears that WC and WHR reclassify risk defined by traditional BMI thresholds,” said Michael J. Blaha, director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease.

“We saw individuals with clinically determined normal weight who had elevated central adiposity and high WHR, associating them with higher risk across most outcomes,” Blaha added.

Why BMI Alone May Not Predict Heart Risk

BMI is calculated by dividing weight in kilograms by height in meters squared and is commonly used to diagnose overweight and obesity. However, BMI does not show where body fat is distributed.

• Visceral fat surrounds the internal organs in the abdominal area and is associated with chronic conditions such as heart disease and diabetes.
• Subcutaneous fat is located directly under the skin and is not as strongly associated with these conditions.

What Did the Study Find?

The study examined whether adding WC and WHR to BMI could better predict future cardiovascular risk. Researchers looked at more than 260,000 people over an average of 20 years. They found that central adiposity could identify cardiovascular risk that BMI alone may miss.

Among people classified as having normal weight by BMI:

• 5% had high waist circumference
• 18% had high waist-to-hip ratio

• 39% had high waist circumference
• 40% had high waist-to-hip ratio

• 9% had low waist circumference
• 45% had low waist-to-hip ratio

People with normal weight or overweight who had clinically defined high WC or WHR had a 15%–50% greater risk for most heart problems.

People with obesity and low WC did not have a significantly different risk of outcomes compared with those who had normal weight and low WC, except for all-cause mortality, for which their risk was significantly lower.

“Our findings emphasize the critical role of identifying elevated central adiposity, even in individuals with a normal BMI or with a BMI in the overweight range. Relying solely on BMI may result in misclassification of cardiovascular risk across a wide range of cardiovascular outcomes,” said Zeina A. Dardari, lead author of the study.

“We encourage clinicians to consider central adiposity distribution across the entire BMI spectrum when evaluating cardiovascular risk in primary prevention settings,” she added.

What Were the Study's Limitations?

The researchers did not have information on several factors that can influence cardiovascular disease risk, including:

• Physical activity
• Diet
• Genetic risk for obesity

The study also included only one assessment of waist circumference and waist-to-hip ratio. This limited the researchers' ability to understand how changes in abdominal fat accumulation over time may influence cardiovascular disease risk.

Organ donation is one of the most profound ways in which we can give the gift of life to another person. World Organ Donation Day, observed every year on August 13, is an opportunity to raise awareness about organ donation, address common myths and encourage more people to consider pledging their organs. India has a large number of patients waiting for organ transplants, including transplants of the liver, kidney, heart, pancreas, intestine and other organs and tissues.

Despite the significant need, organ donation rates remain low, with lack of awareness and several misconceptions continuing to be major barriers. One organ donor can potentially save multiple lives. However, for this to happen, it is important that people understand the process and make an informed decision about organ donation during their lifetime.

Busting Common Myths About Organ Donation

1. “My religion does not permit me to donate my organs.”

2. “Organs can only be donated after the heart stops beating.”

For most organs, donation after brain death is possible when the brain has permanently stopped functioning, but the heart is still beating, which generally occurs in an intensive care setting. Corneas can also be donated after death within a limited time period. This is why pledging your organs during your lifetime and discussing your decision with your family is important.

3. “Organ donation will disfigure or mutilate the body.”

Organ retrieval is performed by trained medical specialists in an operating theatre. The surgical incision is carefully closed after the procedure, and the body is not mutilated.

Also read: Post-Organ Donation And Transplant Care: How Can Donors And Recipients Stay Healthy?

4. “I can buy a kidney or liver for my family member.”

5. “If I donate a kidney, I will become weak or handicapped.”

A healthy person who is found suitable for living kidney donation through the required medical evaluation can generally continue their normal life after donation. The remaining kidney is capable of maintaining normal kidney function.

6. “A kidney donor has to take lifelong medicines.”

Kidney donation does not mean that a healthy donor has to take lifelong medication simply because they have donated a kidney. Some pain medication may be required during the initial recovery period, while the remaining healthy kidney continues to perform its function.

7. “I will have severe dietary restrictions after donating a kidney.”

According to the source material, kidney donors do not generally need specific dietary restrictions solely because they have donated a kidney, as the remaining kidney continues to maintain normal kidney function.

8. “I will not be able to have children after donating a kidney.”

Both men and women who donate a kidney can have children. For women, the source recommends waiting one year after donation before becoming pregnant to allow the body to recover completely.

9. “I am over 60, so I am too old to donate.”

Age alone does not determine whether someone can donate. The health of the donor and the condition of the organs are important considerations, and suitability is determined through medical evaluation.

Also read: World Organ Donation Day 2026: Too Old Or Too Sick To Donate Organs? Doctors Bust Key Myths

What Can We Do To Encourage Organ Donation?

• Consider pledging your organs during your lifetime and communicate your decision clearly to your family.

• Talk to your family, friends and colleagues about organ donation and help dispel common myths.

• Encourage community organisations to participate in creating awareness around organ donation.

• Do not assume that you are medically unfit to donate. A team of medical experts evaluates the donor and determines suitability.

• Organ donation is a completely voluntary decision. No individual should be pressured into donating an organ.

• Patients waiting for an organ transplant should approach a licensed transplant hospital and complete the necessary registration formalities, including through the NOTTO system.

Organ donation is ultimately about giving someone another chance at life. We should not take our organs with us; they can be used to save lives and give hope to those waiting for a transplant.

By Dr Sanjeev Gulati, Chairman, Nephrology, Fortis, Vasant Kunj