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 43-year-old mother from Northern Ireland got diagnosed with an exceptionally rare cancer after months of pain, continual bleeding and abdominal swelling. She said that these symptoms were initially and inaccurately attributed to perimenopause, anxiety and constipation.

Nicola Crymble’s symptoms started in 2024 after she had a copper intrauterine device (IUD) inserted. The bleeding and pain became so severe that she had the device removed while she was in Kenya doing mission work. “I was constantly bleeding, there was so much pain,” Crymble said.

However, her symptoms persisted even after she returned home. She said doctors initially suggested that perimenopause and anxiety could explain what she was experiencing.

By December 2024, Crymble had noticed a lump in her abdomen. It continued to grow, making everyday activities challenging. She said people even thought she was pregnant because of the swelling. She eventually went to hospital and underwent scans, which revealed a mass near her cervix. Doctors initially thought it might be a cyst.

Crymble Got Diagnosed With FATWO, A Rare Cancer

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Crymble underwent major surgery in February 2025 to remove the tumour. She also chose to have her ovaries and fallopian tubes removed during the procedure. A month later, she received the diagnosis that she had female adnexal tumour of probable Wolffian origin, commonly known as FATWO.

The tumour is believed to develop from remnants of the Wolffian duct, an embryonic structure involved in the development of the reproductive and urinary systems. Although these structures usually regress during female development, residual tissue can sometimes pave the way for tumour growth.

FATWO is an exceptionally rare form of cancer. There are only around 150 documented cases recorded worldwide. While many FATWO tumours do not metastatize, some can behave aggressively. In Crymble’s case, the cancer later spread to her liver and vaginal vault, the upper part of the vaginal canal.

She experienced intense pain beneath her ribs before a scan revealed that the cancer had spread. Further surgery was ruled out because the tumour growths were too close to other organs.

Chemotherapy As Surgery Was Not An Option

With surgery no longer an option, Crymble and her doctors decided to proceed with chemotherapy. She began treatment on October 13, 2026, and is expected to undergo six rounds, one every three weeks.

The family is also looking for specialist advice because there is limited information available about the rare disease and the best way to treat it. Her husband, Andrew Crymble, said doctors had little experience with the condition.

“They've never seen it before, they don't know how to treat it,” he said, explaining why the family decided to share her story publicly. They hope it will reach researchers or doctors who may have more information about FATWO.

Crymble has stopped working and has found it difficult to maintain her usual family routines while undergoing treatment. The family is also seeking financial support after discovering that their life insurance coverage will not cover the treatment.

Also read: Amgen & AstraZeneca's New Treatment Combination Cuts Advanced Lung Cancer Death Risk By 58% In Trial

Symptoms That Warrant Immediate Attention

Perimenopause can cause changes in menstrual patterns, like irregular periods. But unexplained bleeding, stubborn abdominal pain, lump or unusual swelling should not automatically be attributed to hormonal changes without seeking medical intervention.

These symptoms can occur due to many causes, and they do not necessarily indicate cancer. But worsening or unusual symptoms demand medical assessment, especially when they do not improve or when new symptoms develop.

The effects of heatwaves, air pollution, noise and overall climate change may extend beyond physical health. According to a new report by the Earth–Brain–Health Commission published in Nature Mental Health recently, they can have a significant impact on mood, cognitive function and overall psychological wellbeing.

The commission warns that environmental changes are altering the conditions in which people live. It also talks about consequences for brain health and mental wellbeing. It also calls for mental health to become a consideration in climate policy, urban planning and environmental decision making, rather than being treated only after symptoms develop.

The findings are relevant to low and middle-income countries, where exposure to environmental hazards can overlap with greater socioeconomic problems like poverty and limited access to healthcare.

“Heat and heatwaves, air and noise pollution, extreme weather and compound events, urbanization, and the loss of green and blue spaces are associated with depression, anxiety, cognitive decline, and impaired emotional and behavioral functioning,” the commission states.

Effects Of Environmental Conditions On Brain

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From biological changes like neuroinflammation, disruption of hormones and the body's internal clock to psychological stress and due to isolation and displacement, the commission identifies several ways through which environmental conditions may impact mental health.

Heat exposure is one of the gravest concerns in current times. Heatwaves can disrupt sleep and contribute to physiological stress, while air pollution can lead to cognitive decline. Noise pollution and stressful urban environments may fuel anxiety and depression.

These exposures are compounded by people’s standard of living. A person living in poorly ventilated housing, for example, may face heat, air pollution, financial hardship and limited access to healthcare at the same time. These combined problems can be difficult to measure by studying each exposure separately.

Who Is At Risk?

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Children, older adults, people with disabilities and marginalised communities may face greater exposure to environmental hazards while having fewer resources and help to cope with them.

The commission also highlights low and middle-income countries and small island developing states. These populations may face significant environmental risks but remain underrepresented in research on climate change and mental health.

Dr Vivek Benegal, senior professor of psychiatry and former head of department at the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, is among the commission's members. He said NIMHANS has been examining how climate change affects the human brain.

Benegal also pointed to a 2023 study conducted by researchers from NIMHANS and King's College London. The study found that even low levels of arsenic exposure, below World Health Organization thresholds, were associated with changes in brain structure and impaired cognitive abilities among children, adolescents and young adults.

Commission's Recommendations

The report recommends that governments should incorporate brain and mental health measures into environmental policies. Its recommendations include monitoring environmental exposures, identifying risks early in life, and designing healthier urban environments.

“The principal obstacles to action are organisational and financial rather than evidential,” the commission observes, noting that research cohorts, Earth-observation systems and environmental governance tools already exist but are often maintained separately.

COVID-19 vaccines were rolled out during the pandemic, so questions about their safety, how long they protect against infection and whether mRNA technology was tested for long enough continue to dominate public debate.

Dr Paul Offit, paediatrician and director of the Vaccine Education Center at Children’s Hospital of Philadelphia and former member of the CDC’s Advisory Committee on Immunization Practices, says many concerns overlook the the evidence collected before and after the vaccines were introduced.

In an interview with HealthandMe, Offit discussed how long COVID vaccine protection lasts, what scientists have learnt about rare side effects and why the technology behind mRNA vaccines was not as new as many people thought.

“I think it is probably the best studied vaccine in human history,” Offit said. He pointed to the large number of people who received them and the safety-monitoring systems used to look for adverse effects.

Why Are People Still Getting COVID After Vaccination?

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The circulation of SARS-CoV-2, the virus that causes COVID-19, is sometimes used to argue that the vaccines do not work. Offit said this misunderstands the type of infection the virus causes and the protection vaccination offers.

“It’s a short incubation period mucosal infection,” he said. “So, vaccination or natural infection will protect you for about four to six months from mild to moderate disease, should protect you for longer against severe disease.”

He compared the future of COVID to influenza, saying that infections will continue even as vaccines help protect against serious illness.

“Even if everybody in the world were vaccinated every year, that virus would still circulate,” he said. “This virus is now with us forever.”

Offit said the goal of COVID vaccination is not necessarily to prevent every infection. It is to reduce the risk of hospitalisation and death, particularly among people most likely to develop severe disease.

“The goal of the vaccine is to keep you out of the hospital and to keep you from dying,” he said.

He said that people over 75, those with chronic heart or lung disease, pregnant women and people with weakened immune systems are at higher risk of developing severe complications from COVID. He said these groups should receive a vaccine every year.

Dr Paul Offit On COVID Vaccine’s Side Effects

Also read: American COVID Drives Cases And Deaths In UK: Unusual XFG Symptoms To Watch For

When COVID vaccines were first authorised in December 2020, the clinical trials involved approximately 35,000 participants across the Pfizer-BioNTech and Moderna studies, Offit said. Some rare side effects of the vaccine became apparent only after the vaccines were administered to much larger populations.

One such side effect was myocarditis, an inflammation of the heart muscle, and, less commonly, pericarditis, which affects the lining around the heart.

“Very quickly, it was found to be a rare cause, roughly 1 in 50,000 myocarditis,” Offit said, referring to mRNA COVID vaccines. He said cases were seen primarily in males aged 16 to 29 and were generally short-lived.

Current evidence confirms that myocarditis and pericarditis are rare but recognised risks associated with mRNA COVID vaccines. The risk has been observed most often in adolescent and young adult males, particularly within seven days after a second dose.

In June 2025, the US Food and Drug Administration required updated safety warnings for the Pfizer-BioNTech and Moderna vaccines. The FDA also noted that some patients in follow-up studies continued to show signs of heart muscle injury on MRI scans, with improvement in some cases. The long-term significance of these findings remains under investigation.

Offit also cited the example of Johnson & Johnson COVID vaccine, which was associated with a rare but serious condition involving blood clots and low platelet counts. The vaccine was no longer available in the US by May 2023.

“You're always looking and trying to find any rare side effect that's associated with the vaccine,” he said.

He added that concerns about stillbirths and pregnancy outcomes had circulated despite research examining vaccination during pregnancy.

Offit said there was “no evidence of congenital malformations, no evidence of premature birth or spontaneous abortion” in the studies he was referring to.

How Long Were mRNA COVID Vaccines Tested?

Another common concern is that mRNA COVID vaccines were developed too quickly and that the technology had not been studied for long enough. Offit disagreed, saying that the technology was not entirely new.

“I think it was studied for a long time,” he said. He pointed to research into mRNA as a vaccine platform that began decades before the COVID-19 pandemic.

“Drew Weissman and Katie Carrico met in 1997 and started working on mRNA as a vaccine platform, for which they won the 2023 Nobel Prize in Medicine,” Offit said.

He also referred to efforts to develop mRNA vaccines against SARS, the coronavirus that caused an outbreak in 2002 and 2003.

“But we really had, really since 1997, information about this vaccine, so like more than 20 years of studies of that vaccine,” he said. “People think it was a new vaccine, but it really wasn't that new.”

The technology had been studied before COVID-19, although the pandemic vaccines themselves still required clinical trials to establish their safety and effectiveness. After their introduction, researchers continued monitoring them to identify rare adverse events.

Do Benefits Of COVID Vaccines Still Outweigh The Risks?

Offit said the decision to vaccinate should take into account both the risk of side effects and the risk posed by COVID itself. “I'm an older person, so I'm going to get a COVID vaccine every year because I think that the benefits clearly outweigh the risks,” he said.

He argued that COVID continues to cause hospitalisations and deaths, making protection against severe disease an important consideration.

He said that the benefits outweigh the risks, particularly for people at higher risk of serious illness. Individual decisions should also take account of age, underlying health conditions, previous vaccination and current medical guidance.