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.

Spending hours sitting at a desk, gaming or binge-watching shows without moving may increase the risk of blood clots, including deep vein thrombosis (DVT), vascular experts have warned.

Prolonged sitting slows blood flow from the legs, potentially increasing the risk of clot formation. Experts from the Vascular Society of India (VSI) highlighted the concern at the VSI-ASVS 2026 Conference, noting that sedentary screen habits warrant attention even among young, otherwise healthy people.

“In our OPD, we are seeing patients where lifestyle history has become an important part of the vascular evaluation. Earlier, when we thought about prolonged immobility, we primarily discussed long-distance travel, hospitalization or being bedridden. Today, we also need to ask young patients how many hours they spend continuously sitting in front of a gaming console, computer or OTT screen,” said Dr. Tarun Grover, Senior Director of Peripheral Vascular and Endovascular Sciences at Medanta.

What Is DVT?

Deep vein thrombosis (DVT) occurs when a blood clot forms in a deep vein, usually in the legs. If the clot travels to the lungs, it can cause a potentially life-threatening pulmonary embolism.

Although prolonged immobility has traditionally been associated with long-distance travel, hospitalization and bed rest, experts say extended screen time can also contribute to inactivity.

Gaming and binge-watching do not automatically cause DVT. However, prolonged sitting may add to the risk, particularly in people with obesity, dehydration, smoking habits, hormonal risk factors, inherited clotting disorders or a previous history of thrombosis.

Also read: Richard Branson’s Wife’s Death Highlights Blood Clot Risk After Fractures

What Does Science Say?

A 2024 systematic review and dose-response meta-analysis published in Scientific Reports, covering 25 articles and 31 studies, found that people with the highest levels of sedentary behavior had approximately 24% higher risk of venous thromboembolism (VTE) than those with the lowest levels.

The analysis also found a 2% increase in VTE risk for every additional hour of sedentary behavior per day. The association persisted after accounting for physical activity, suggesting that exercise may not fully offset the potential risks of prolonged sitting.

The experts explained that when people sit for hours, their calf muscles—which help pump blood back toward the heart—remain relatively inactive, slowing venous circulation.

A separate study of 11 adolescents with thrombosis found that all reported at least four hours of daily screen exposure, averaging approximately six hours. Eight had DVT in the legs, two had pulmonary embolism and one had subclavian vein thrombosis.

Many also had inherited thrombophilia, a predisposition to blood clots. Researchers noted that prolonged screen-related inactivity may act as an additional trigger rather than the sole cause of thrombosis.

“The evidence showing a 24% higher VTE risk with higher sedentary exposure should make us take this issue seriously. A young age should not create a false sense of security, particularly when prolonged sitting is combined with other risk factors,” Dr. Grover said.

How Can You Reduce The Risk?

Experts recommend taking regular movement breaks during work, gaming and streaming sessions to avoid prolonged uninterrupted sitting.

“Just as smoking increases vascular and clotting risks, prolonged sitting can also increase the risk of blood clots. When a person remains seated for hours, the calf-muscle pump becomes inactive, venous blood flow from the legs slows down and blood can stagnate in the deep veins," said Dr. Bhupesh Garg, Senior Vascular and Endovascular Surgeon, Vascular Society of India.

The message should be simple: if you are going to spend hours on a screen, do not spend those hours completely still, the experts said.

The Black Death swept across Eurasia and North Africa between 1346 and 1353, killing an estimated 30% to 60% of Europe's population.

Plague continued to recur in Europe over subsequent centuries, causing millions of deaths. Caused by Yersinia pestis, the same bacterium responsible for plague today, the Black Death was primarily associated with bubonic plague, although pneumonic plague also occurred.

Bubonic plague typically spreads through infected flea bites, while pneumonic plague affects the lungs and can spread between people through infectious respiratory particles during close contact. All forms can be fatal without prompt treatment, but antibiotics are effective when administered early.

India's 1994 Plague Outbreak

Although often associated with medieval history, plague continues to occur in parts of the world.

In 1994, India experienced an outbreak involving both bubonic and pneumonic plague, following heavy flooding and reports of exposure to dead rats.

“When the plague outbreak happened in India, I was one of the people who investigated it. The outbreak involved bubonic plague, which can be treated with antibiotics, and Surat also saw 64 to 68 cases of pneumonic plague. We identified the plague bacillus and traced its cycle in the surrounding wildlife. Plague surveillance in rats and other animals is essential to detect outbreaks early and take preventive measures,” Dr. N.K. Ganguly, former Director General of the Indian Council of Medical Research (ICMR), told HealthandMe.

There were 693 suspected cases that tested positive for Yersinia pestis antibodies and 56 deaths nationwide.

Surveillance, hygiene and timely treatment were essential to controlling the disease, said Dr. Amitabh Banerjee, an epidemiologist and former member of the Indian Armed Forces’ mobile epidemic investigation team. He investigated the 2002 pneumonic plague outbreak in Himachal Pradesh, which caused 16 cases and four deaths.

Plague Still Exists In Africa And The US

In the US, an average of about seven human plague cases are reported annually, mostly in rural areas of the American West, according to the Centers for Disease Control and Prevention (CDC).

The continued presence of Yersinia pestis in animal populations means the disease has not been eradicated.

“People think the plague is gone, it was something that occurred 500 years ago. It's not. It's here amongst us,” Simon Clarke of the University of Reading in the UK told the Associated Press. “Unless you get rid of those wild animals, which of course is not possible, then you're not going to get rid of the bacteria.”

Russia's Plague Scare: What We Know

Russia has completed checks following the October 2 death of 28-year-old laboratory worker Darya Shipilova in Siberia. Authorities have not confirmed plague as the cause, describing her illness as pneumonia of unknown origin. Nearly 5,000 samples reportedly showed no dangerous pathogens.

Reports of a second death linked to the plague was called "fake news" by Russia, and no plague outbreak has been confirmed in Russia. The WHO and US have requested Russia for more transparency regarding the cases.

Can Plague Be Eradicated?

Plague persists because Yersinia pestis circulates naturally among wild and domestic animals, including rodents, and their fleas. Eliminating human cases in one location does not remove the bacterium from these animal reservoirs.

Dr. Banerjee said plague can be deadly, particularly when it affects the lungs, but modern antibiotics are highly effective when treatment begins early.

“Plague cannot be eradicated because it is in wildlife, it is in rodents and all. So the only thing is hygiene and, with modern antibiotics, there should not be any panic,” he told HealthandMe.

Bubonic plague does not typically spread directly between people, while pneumonic plague can spread through infectious respiratory particles during close contact. Pneumonic plague can progress rapidly and requires urgent treatment.

Dr. Banerjee cautioned against assuming that a suspected case automatically signals a wider outbreak, noting that early diagnosis and appropriate antibiotic treatment are crucial.

Indian jewelery designer Saba Ali Khan, daughter of veteran actress Sharmila Tagore and cricketer Mansoor Ali Khan Pataudi, has opened up about her brain tumor diagnosis at the age of 27.

Speaking on her sister, actress Soha Ali Khan’s podcast, Saba recalled that her diagnosis came as a surprise, without common warning signs such as headaches or vision loss.

Dr. Mazda K. Turel, the neurosurgeon who treated her at Wockhardt Hospitals, Mumbai, told HealthandMe that people with brain tumors can be “walking, talking and functioning normally” despite having a potentially serious tumor. He explained why tumors can go unnoticed and which symptoms warrant medical attention.

How Saba Ali Khan Discovered Her Brain Tumor

Saba recalled fainting while out with a friend. After losing consciousness a second time, she took around 20–25 minutes to regain consciousness.

An MRI revealed a shadow in the third ventricle of her brain. Doctors initially diagnosed a colloid cyst, a rare, non-cancerous growth.

Six months later, she underwent surgery and was diagnosed with pilocytic astrocytoma, a slow-growing, generally low-grade tumor of the brain or spinal cord.

Also read: Survival In Aggressive Brain Tumors Improves By Up To 50% in India, Say Doctors

Why Brain Tumours Go Undetected In Young Adults

“Brain tumors don’t check your age before making an appearance,” Dr. Turel said. “In young adults, symptoms are often dismissed as stress, migraines, fatigue or lack of sleep. Some tumors grow slowly, allowing the brain to adapt remarkably well.”

“The brain has an extraordinary ability to compensate, especially when a tumor grows slowly or develops in a relatively silent area,” he explained.

Early signs may include persistent headaches, subtle personality changes, difficulty concentrating, blurred vision and unexplained seizures. Other clues include forgetting familiar words, unexplained irritability, occasional imbalance and brief episodes of staring or losing awareness.

Sometimes, family members notice changes before the patient does. Dr. Turel illustrated the difference between ordinary forgetfulness and a potentially concerning change: “If you forget keys, that is OK, but if you forget what the keys are for,” it is a sign to get checked.

“The problem is that these symptoms are common, but their persistence or progression is what deserves attention,” he told HealthandMe.

How Tumor Location Affects Symptoms

Read More: Can 'Eye Strain' Lead To Brain Cancer? Experts Explain

Symptoms often depend more on where a tumor is located than on its size, Dr. Turel explained.

• Frontal lobe: Changes in personality or judgement.
• Temporal lobe: Memory problems or unusual seizures.
• Visual pathways: Blurred or double vision.
• Cerebellum: Problems with balance and coordination.

“New speech difficulties, weakness, unexplained seizures or progressive cognitive changes should never be casually dismissed,” he warned.

Brain Tumor Or Migraine: When Should A Headache Worry You?

Migraines usually follow a recognizable pattern and may involve nausea or sensitivity to light and sound, Dr. Turel said.

Tumor-related headaches are more concerning when they are new, progressively worsening, different from previous headaches or accompanied by neurological changes. They may be worse in the morning or with coughing and straining, although this is not always the case.

A persistent headache that progressively worsens, wakes someone from sleep or occurs with vomiting, visual changes or neurological symptoms warrants medical evaluation.

"A sudden, explosive headache that reaches maximum intensity within seconds—a thunderclap headache—is a medical emergency," the neurosurgeon said, noting that it can occur while "walking, talking and functioning normally"

It may indicate bleeding around the brain from a ruptured aneurysm rather than a tumor. Sudden weakness, confusion, loss of consciousness or a first seizure also require emergency assessment.

“Most headaches are not caused by brain tumors, and a headache alone rarely indicates one. The key is not to panic about every headache, but to recognize when an old familiar headache begins behaving like a stranger,” Dr. Turel said.