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.

After Dussehra festivities, Delhi woke up to an alarming AQI of 300, maybe even more in some parts of the city. On October 21, pollution curbs under GRAP-1 were implemented, which are brought in force when AQI ranges between 201 and 300.

As Delhi's air pollution increases, some people may experience uncommon symptoms like feeling unusually tired, sluggish or unable to concentrate. This is not just a coincidence. Even people without asthma or breathing difficulties can feel fatigue, especially during periods of high air pollution.

Fine particulate matter (PM2.5) can penetrate deep into the lungs and trigger inflammation and physiological stress. Its effects may extend beyond the respiratory system, affecting blood vessels health, cardiovascular function as well as sleep.

HeathandMe spoke to Dr Puneet Khanna, Chairman, Respiratory Medicine and Pulmonology, Manipal Hospital Dwarka, New Delhi, Dr. Puneet Gupta, HOD - Pulmonology, Intervention Pulmonology & Sleep Medicine, Yatharth Super Speciality Hospital, Noida Extension, and Dr Mrinal Sircar, Director, Respiratory and Sleep Medicine, Medanta, Noida, who explained why rising AQI can leave some people feeling exhausted, what can help and when chronic fatigue needs medical attention.

High AQI May Make You Feel Tired Even Without Breathing Problems

Poor air quality does not affect just the lungs. Dr Sircar explains that air pollution can cause symptoms even in people without a pre-existing respiratory condition.

According to Dr Khanna, exposure to PM2.5 can trigger inflammation and oxidative stress, increase the body's workload and affect sleep quality. These changes may contribute to tiredness, headaches, low energy and reduced concentration, even in people with otherwise healthy lungs.

“Exposure to polluted air may also affect sleep quality and increase the body's overall stress response, contributing to symptoms such as tiredness, reduced energy and difficulty concentrating,” he says.

Dr. Gupta delves deeper into the process of PM2.5's attack and how the body responds to it.

He explained, "Your immune system treats fine particles (PM2.5) as intruders and mounts a constant low-grade defence, which burns energy much like a mild infection. At the same time, irritated airways and gases like carbon monoxide can make oxygen delivery slightly less efficient. The most underrated cause is sleep: a dry throat, blocked nose, and mild night-time cough fragment your sleep, so you wake up unrefreshed without knowing why. Fatigue here doesn’t mean your lungs are weak. It means your body is working overtime quietly."

Also read: Sky Turns Orange In Indonesia: How Toxic Smog From Wildfires Can Impact Health

Can PM2.5 Affect The Heart And Blood Vessels Too?

PM2.5 particles are small enough to penetrate deep into the lungs. Some of its components can even enter the bloodstream. Exposure can trigger inflammatory and oxidative stress responses beyond the respiratory system.

Dr Khanna says, “These changes may reduce physical endurance, increase feelings of fatigue, and contribute to symptoms such as brain fog, lethargy, and reduced exercise tolerance, particularly during periods of severe air pollution.”

Dr. Gupta explained PM2.5 can create the same response from body as a common flu does. But the extent of these effects depends on pollution levels, duration of exposure and individual risk.

He said, "PM2.5 is small enough that it, or the inflammatory chemicals it triggers, can enter the bloodstream. Signalling molecules such as IL-6 and CRP then travel through the whole body and produce the same “wiped out” feeling you get with the flu."

He also said that particles also create oxidative stress, which damages mitochondria, the power plants of your cells. Blood vessels become stiffer, blood pressure can rise slightly, and the nervous system’s control of heart rhythm can be disturbed, which may feel like heaviness or palpitations. Inflammation can also reach the brain, causing fog and poor focus.

Also read: Delhi Smog: Can You Really Tackle Pollution Season With An N95 Mask And Air Purifier?

What Can Help?

According to the doctors, the key is to reduce exposure to polluted air. Practical steps include:

• Limit exertion: Avoid strenuous outdoor activity when pollution levels are high, especially during periods of severe pollution.
• Wear a well-fitting N95 respirator: It can reduce exposure to fine particles when outdoors.
• Improve indoor air quality: Keep windows closed when outdoor air quality is poor and use a suitably sized air purifier with a HEPA filter where feasible.
• Maintain basic health routines: Get adequate sleep, stay hydrated and eat regular meals.
• Check AQI levels: Use local air quality updates to plan outdoor activities.

Dr Khanna emphasises that these steps can help reduce exposure but cannot eliminate the effects of ongoing pollution. He also said that severe breathlessness, chest pain, fainting or sudden weakness requires urgent medical attention.

Does Pollution-Induced Fatigue Go Away When AQI Improves?

For many otherwise healthy people, symptoms can improve once air quality improves. Dr Khanna says recovery may occur within a few hours to several days, depending on pollution severity, exposure duration and individual health.

However, there is no fixed recovery timeline. People with underlying respiratory or cardiovascular conditions may take longer to recover, while persistent tiredness may point to another health problem.

Dr Sircar advises seeking medical advice if fatigue continues after air quality improves.

The doctors also advise that if fatigue is chronic, recurrent, worsening or interferes with daily activities, medical evaluation should be sought rather than simply attributing it to air pollution.

Dr Sircar also says that that a doctor may need to investigate other possible causes, including anaemia, thyroid disorders, sleep problems and cardiovascular conditions. Fatigue accompanied by a chronic cough, wheezing, breathlessness, chest problems or reduced exercise tolerance also needs intervention.

A single photograph of someone’s face might carry real clues about their health and how long they’re likely to live, at least according to new AI tools built by researchers at Mass General Brigham in Boston.

What the researchers built

The team trained a large AI foundation model called FAHR-Face, short for Foundation Artificial Intelligence for Health Recognition, on more than 40 million facial images.

From that base model, they built two specialised tools: FAHR-FaceAge, which estimates a person’s biological age from a single photo, and FAHR-FaceSurvival, fine-tuned on 34,389 photos of cancer patients to predict survival risk directly from facial appearance.

“I was pretty surprised to find out that we could pick up signs of mortality risk from just a facial photograph,” corresponding author is Dr. Raymond Mak, a radiation oncologist at Mass General Brigham Cancer Institute told CNN. The study is published in The Lancet Digital Health.

What the two tools actually look at

The two algorithms focus on entirely different parts of the face. “The age estimation algorithm is looking at the area around the temples, the area on the forehead, above the eyes and then what we call the nasolabial fold,” Mak said, while “the mortality risk prediction algorithm is looking at a totally different part of the face... the bridge of the nose and the area under the eyes.”

Also Read: ADHD Linked To 71% Higher Risk Of Death; Suicide And Injuries Among Top Concerns

The results

Among 122 cancer patients flagged by FAHR-FaceSurvival as high-risk, 52.5% died within 90 days, compared with about 2% of the 975 patients in the lowest-risk group. Separately, 21% of patients whose biological age came back more than 20 years older than their actual age died within 90 days, against about 6% of those whose biological age was at least 10 years younger than their chronological age.

The researchers also found that cosmetic changes, including surgery, Botox, or makeup, didn’t throw off the models’ performance, according to the Mass General Brigham release.

An eerie echo of ancient medicine

The facial regions both AI models rely on, the nose, temples, and the area around the eyes, closely match what the Greek physician Hippocrates described around 400 BC in his Book of Prognostics as signs of approaching death: “the nose sharp, the eyes sunken, the temples fallen in.”

Mak told CNN the algorithms had no exposure to Hippocrates’ text and were trained purely on photographs and outcomes data. “Hearing Hippocrates echo over millennia in our algorithms was very eerie,” he said.

Not ready for the clinic yet

Outside experts urged caution. Dr. Wilbur Lam of Emory University, who wasn’t involved in the study, called it “an extremely compelling study” with robust associations, but said its “true clinical utility... will need to be demonstrated prospectively,” and flagged open questions about how well it performs across different facial features, skin tones, and age groups.

Miroslaw Bober of the University of Surrey, also not involved in the study, said the findings shows “convincing evidence” of a statistical link but cautioned that “predicting an outcome is not the same as explaining it.”

He noted the study never tested whether the AI model picks up anything a doctor’s own assessment wouldn’t, since doctors’ general health evaluations weren’t measured for comparison. “This is a promising proof of concept, but it is not ready for clinical use,” Bober said.

An individual's income, education, gender and place of residence can impact their risk of developing chronic diseases, as well as their access to diagnosis and treatment, according to a new World Health Organization (WHO) report.

The report highlights how social and economic inequalities affect the burden of noncommunicable diseases (NCDs) like cancer, cardiovascular diseases, diabetes and chronic respiratory diseases.

Published on October 20, State of Inequality: Noncommunicable Diseases and Their Risk Factors is WHO's first comprehensive global assessment of inequalities in NCDs and their risk factors. The report is based on data sources from nine countries and examines 35 indicators, using national data that collected over the past decade.

NCDs account for about three-quarters of deaths worldwide but their impact is not shared equally across different countries and their populations. The report examines how differences in economic status, education, sex, age, disability, employment, migration status and location influence disease risks and access to healthcare.

“This is the first effort to systematically measure inequalities in NCDs and their risk factors on a global scale,” said Dr Ahmad Reza Hosseinpoor, who leads WHO's health inequality monitoring team. “The findings show which populations are being left behind.”

How Income And Education Influence Chronic Disease Risk

The report found that people with lower levels of education in low and middle income countries tend to have higher rates of hypertension and diabetes.

Education can affect access to credible health information, opportunities to make informed health decisions and the capability to navigate technically complex healthcare services.

Income becomes a key factor that affects whether people's ability to afford nutritious food, preventive care, medicines and routine medical check-ups.

The report found that the poorest and least-educated women were less likely to receive cervical cancer screening. Tobacco use was also higher among men who were less educated than their educated counterparts.

Also read: G155E H1N1 Mutation In US Raises Concerns: Can This Year’s Flu Shot Still Protect You?

Risk Is Also Affected By Gender And Location

Differences in healthcare access and risks were also observed between men and women. Men were more likely to use tobacco and consume alcohol, but men with hypertension were less likely to be diagnosed and treated than women.

Women were less likely to meet recommended physical activity levels, while obesity was more common among women, particularly in low and middle-income countries.

Geography was another key factor as in many underprivileged countries, people living in rural areas had less access to hypertension diagnosis and treatment, as well as cervical cancer screening.

Rural households could also face greater exposure to household air pollution, while urban populations often experienced greater exposure to outdoor air pollution.

People with disabilities and migrants may also face financial, administrative, geographical or language barriers that make prevention, screening and treatment harder to access.

Also read: Lead Poisoning: WHO Warns There Is No Known Safe Level; Flags Risks From Paint, Spices and Cookware

What Needs To Change According To WHO

WHO said countries should use inequality data to identify marginalised populations who face barriers to enable direct prevention and treatment services towards them.

The report recommends expanding interventions to reduce NCD risks, improving access to screening and treatment in weak communities, and collecting data that reveal differences between population groups.

“Inequality data are not simply about documenting differences – they are a tool for action,” said Dr Alain Labrique, director of WHO's Data, Digital Health, Analytics and AI Department. “They help countries better tailor policies and programmes, identify gaps in coverage and track whether progress is reaching all population groups.”