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.

The suspected plague situation in Russia has reportedly claimed another life, fueling fears of a potential outbreak. However, Russia has not confirmed that either death was caused by plague, and investigations into the cases are ongoing.

India, which has witnessed plague outbreaks in the past, including the 1994 Surat outbreak and a pneumonic plague outbreak in Himachal Pradesh in 2002, also has rodent populations that can serve as reservoirs for plague. But does the situation in Russia pose a risk to India if plague is eventually confirmed?

To understand the potential risk to India, HealthandMe spoke to two experts with experience investigating plague outbreaks in India.

Plague From Test-Tube Exposure?

Also read: Russia Plague Scare: Is Pneumonic Plague Deadlier Than Bubonic & Septicemic Plague?

The death of a 28-year-old laboratory worker in Russia’s Irkutsk region has raised concerns about possible plague exposure. Reports said she may have accidentally broken a test tube containing Yersinia pestis, the bacterium causing plague, while collecting samples. However, Russian authorities have not confirmed plague and said she died of pneumonia of unknown cause.

Dr NK Ganguly, former Director General of the Indian Council of Medical Research (ICMR) told HealthandMe that the case has not been established as plague and questioned whether a test-tube exposure could explain plague pneumonia.

“Actually, the case in Russia has not been proven to be plague. It has been reported as a case of unknown cause and undiagnosed pneumonia. They have been investigating plague among about 2,000 people in the vicinity, as well as among people in the laboratory. So, they have not confirmed it as a plague case. And from a test tube exposure, it is difficult to have plague pneumonia.”

Unconfirmed reports have also claimed another death linked to the same laboratory, but this has not been independently verified.

Dr Ganguly was one of the people who investigated the 1994 plague outbreak in Maharashtra’s Beed district.

Should India Be Concerned?

There is currently no indication that the situation in Russia poses a significant pandemic risk to India.

Dr Ganguly said there is no reason for India to be very concerned about the Russian situation, particularly because plague has not been confirmed.

“So from the Russian plague, there is no, we need not be very worried. Firstly, they have not reported it as plague. It might be plague, but they have not reported it as plague.”

The WHO has also assessed the risk to the wider population as low. WHO spokesperson Christian Lindmeier said the initial assessment based on available information put the risk at moderate to low for Irkutsk, low for Russia as a whole and very low for the WHO European Region.

How Does Plague Spread?

Plague is caused by the bacterium Yersinia pestis and is primarily associated with rodents and their fleas. It can occur in different forms, including bubonic, septicemic and pneumonic plague. Russia is suspected to have pneumonic plague.

Dr Amitabh Banerjee, who investigated the Himachal Pradesh plague outbreak in 2002, said plague does not typically spread rapidly from person to person.

“So it's not a very quick transmission, particularly person to person. But plague is a disease which 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.

Banerjee also noted that pneumonic plague can be severe, while bubonic plague does not typically spread easily from person to person.

“So pneumonic plague can be very deadly particularly pneumonic plague and that will be localized pandemic it is not possible because those persons will be very sick, they cannot move out or not and bubonic plague will not transmit very easily from person to person and both are treatable…”

How Should India Prepare?

While Dr Ganguly said there is no immediate reason for India to be worried about the Russian situation, he stressed the importance of continued surveillance of rodents and other animals, particularly where wildlife and human habitation overlap.

“So the main thing is that go on doing surveillance in the rats and other, in the vicinity of where the forest and the human habitat march. And whenever you find any activity, then take preventive precaution.”

Leaving Delhi for a city with cleaner air could be a health-smart decision as it can reduce your exposure to harmful pollutants. But just because you are away from the smog, it does not mean the health effects from years of inhaling polluted air will recover overnight.

That brings us to an important question. How long do lungs take to recover after living in an excessively polluted environment?

Air pollution, particularly fine particulate matter known as PM2.5, triggers inflammation and oxidative stress throughout the body. This can directly impact the lungs, heart, blood vessels and even the brain.

The World Health Organization says long-term exposure to air pollution increases the risk of serious disorders like heart disease, stroke, chronic obstructive pulmonary disease (COPD) and lung cancer. That is why relocating could be beneficial without necessarily being a complete reset for the body.

Exposure Stops But Not Effects

Also read: Delhi Air Pollution Is Back: What Days Of Poor AQI Can Do to Your Lungs

The key difference to note here is between ongoing exposure and the damage that exposure may have contributed to. Once someone moves to a place with cleaner air, they are no longer receiving the same daily dose of pollutants. This can alleviate the ongoing inflammatory burden due to toxic air significantly.

But if years of exposure have contributed to changes in lung function, blood vessels or cardiovascular health, those effects may take much longer to recover, and some chronic disease may not even be completely reversible.

A recent study examining Delhi’s pollution between 2019 and 2023 found that PM2.5 levels exceeded India’s national daily standard on roughly 60% of measurements and the WHO daily guideline on almost all days.

Researchers also found that particles deposited deep in the lungs can be cleared much more slowly than larger particles, sometimes over weeks to years.

Lungs May Be Impacted For A Long Time After Moving

Also read: Children, Adults & Seniors: How Lung Health Risks Change Across Life Stages

PM2.5 particles are small enough to travel deep into the respiratory system. Some particles can reach the alveolar regions of the lungs, where clearance and recovery are slower. Constant exposure can also keep irritating the airways, worsening conditions like asthma and contributing to long-term respiratory disease.

WHO notes that short-term exposure can aggravate asthma and increase respiratory infections, while chronic exposure is associated with diseases such as COPD and lung cancer.

The consequences of air pollution on health are not just limited to breathing. PM2.5 can contribute to inflammation and oxidative stress, while some particles can enter into the bloodstream. This can affect blood vessels and the cardiovascular system.

Long-term exposure has also been associated with atherosclerosis, heart attacks and stroke, among other cardiovascular outcomes. The US Environmental Protection Agency says evidence links both short and long-term PM2.5 exposure with changes in heart and blood-vessel function and with cardiovascular disease.

Recovery After Moving Away

Reducing exposure could be an excellent health intervention to start the recovery process. Once a person is no longer repeatedly exposed to high concentrations of PM2.5 and other pollutants, the body is no longer subjected to its active effects.

But recovery also depends on what has happened during the years of exposure. Temporary inflammation or irritation may improve after exposure falls, while structural changes or chronic diseases may persist for quite a while even after moving away.

It is therefore more accurate to think of relocation as reducing future exposure rather than expecting to escape pollution health effects scot-free.

Delhi’s pollution crisis is not confined to a few extremely bad winter days. Research analysed five years of AQI data and found persistently high PM2.5 and PM10 concentrations. It also found that pollution generally worsened during post-monsoon and winter months. Evening commuting periods also produced higher particulate deposition than morning periods.

In my 13 years of working with clients as a trauma-informed consulting psychologist, I have often noticed that people recognise nervous-system overload only after their body forces them to slow down.

Until then, they may describe themselves as “too sensitive”, “lazy” or “unable to cope”. In reality, these reactions are often the nervous system’s attempt to protect us.

Fight, Flight, Freeze Or Shutdown

Our nervous system continually assesses whether we are safe. When stress feels persistent or overwhelming, the body may move into fight or flight.

We might become irritable, restless, anxious or unusually controlling. The heart may race, muscles tighten and sleep become disturbed. At other times, the system may shift towards freeze or shutdown, showing up as exhaustion, emotional numbness, procrastination, forgetfulness or a strong desire to withdraw.

Also read: LSD-Based Treatment Clears Second Phase 3 Trial: Could It Be The First New GAD Drug In 2 Decades?

When Everyday Reactions May Signal Overload

For example, someone who becomes disproportionately angry over a minor delay may not simply have an “anger problem”; their system may already be carrying days or months of accumulated stress. Another person may sit before a simple email for hours, unable to respond.

What looks like avoidance may actually be a freeze response. Some people remain highly productive while feeling disconnected from their bodies, until headaches, digestive difficulties or fatigue begin demanding attention.

These signs do not automatically indicate trauma or a mental health condition. They are invitations to become curious: What has my system been carrying? When did I last feel rested, supported or genuinely safe?

Small Ways To Help The Body Feel Safer

If you notice these patterns, begin gently. Reduce unnecessary stimulation, eat regularly, protect your sleep and spend time with people around whom you do not have to perform. Slow breathing—particularly allowing the exhale to be longer—may help signal safety. You can also look around the room, notice your feet on the floor and name what you can see and hear. Small, repeated experiences of safety are often more helpful than forcing yourself to “calm down”.

If symptoms persist, interfere with daily life or feel difficult to manage alone, speaking with a trauma-informed therapist can help you understand the patterns beneath them. Therapy is not only for moments of crisis; it can offer a safe space to listen to what the nervous system has been communicating all along.

The body is rarely working against us. Often, it is asking for care in the only language it knows.

By Ms Arouba Kabir, Psychologist & Therapist, Founder - Enso Wellness