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 discrepancy between Pennsylvania’s reported measles-associated deaths and the US Centers for Disease Control and Prevention’s national tally sparked a political and public-health controversy.

In an exclusive interview with HealthandMe, 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, accused US Health Secretary Robert F. Kennedy Jr. of adopting a “see-no-evil approach” to the outbreak.

He criticised the Trump administration’s handling of measles deaths, the proposal to split the measles, mumps and rubella (MMR) vaccine, and a new federal initiative to expand vaccine-injury reporting.

Pennsylvania reported six measles-associated deaths, according to its Department of Health. The CDC, meanwhile, had confirmed two deaths.

The figures have become the focus of a dispute over how deaths among measles patients should be classified and included in government data.

‘These Are Measles-Related Deaths’: Dr Paul Offit On CDC’s Death Toll

Also read: US Shelved Poultry Vaccination Due To RFK Jr’s Vaccine Skepticism: Can Vaccine Help Control Bird Flu?

During the interview, Offit spoke about the discrepancy between Pennsylvania’s report of six deaths and CDC’s count of two. “These are measles-related deaths,” he said, arguing that measles had contributed to the deaths reported by the state.

“Had these children or adults not had measles, in the case of the one-day-old and few-month-old, they would have never died,” Offit said.

He accused Kennedy of refusing to acknowledge the state’s report and said the federal government’s approach risked obscuring the seriousness of the outbreak.

“This is just Robert F. Kennedy Jr. refusing to acknowledge the fact that he is an excellent anti-vaccine activist,” Offit said.

The disagreement involves more than a difference in numbers. Pennsylvania health officials count deaths that meet the state’s epidemiological definition of measles-associated fatalities.

The federal government has moved towards requiring confirmation through the National Center for Health Statistics. It now considers the fact that measles is listed as the underlying cause of death before including a fatality in its tally. This process can take longer than state reporting.

A death occurring in someone with measles does not automatically establish that the infection caused the death. However, measles can lead to serious complications, including pneumonia and brain inflammation, which can be fatal.

US Measles Outbreak Is ‘The Tip Of A Much, Much Bigger Iceberg’

Also read: Sixth Measles-Associated Death Reported In Pennsylvania As Cases Cross 1,100

Offit said the reported number of measles cases in Pennsylvania could substantially underestimate the actual scale of transmission. “You can assume that's off by a factor of at least five. I think there's between 5,000 and 10,000 cases of measles in our state,” he said during the interview.

Pennsylvania’s Department of Health reported 1,260 confirmed cases across 42 counties as of October 16, alongside 225 hospitalisations. “So this is the tip of a much, much bigger iceberg,” Offit said.

He also highlighted the risk among adults who may neither have acquired immunity through previous infection nor received vaccination.

“The thing that strikes me about measles right now is it's an adult disease,” he said, pointing to people in their 20s, 30s and 40s who may remain susceptible.

Offit argued that the resurgence should be attributed to failure to vaccinate rather than a failure of the vaccine itself. “Certainly not a vaccine failure. The vaccine doesn't work if you don't get it,” he said.

On MMR Split Proposal

Also read: Trump Signs Order To Change Childhood Vaccine Schedule Amid Measles Outbreak, Split MMR Into Three Shots

While addressing the measles crisis in the United States, Offit also addressed President Donald Trump’s proposal to separate the combined MMR vaccine into three individual shots.

The MMR vaccine has been used for decades. Trump’s executive order to split the vaccine had revived a debate that the combined vaccine causes autism, which has been discredited.

He referred to research conducted over several decades that has not established a causal link between MMR vaccination and autism. “There was the MMR vaccine in 1971. So we've had 50 plus years of the MMR vaccine,” he said.

Offit argued that separating the vaccines would increase the number of injections children receive without providing an established benefit.

“There's no reason to do it. Just makes it more expensive, less available, and has a longer period of time when children aren't getting vaccines,” he said. “And they get six shots instead of two for no benefit.”

He also said the proposal had made parents more skeptical about vaccination.

The debate sparked concerns as delaying vaccination can leave children susceptible to measles during the period before they receive protection. Any changes to vaccine schedules or formulations need to be assessed against evidence of safety, effectiveness and practical consequences for vaccine access.

On RFK Jr.’s Vaccine-Injury Reporting Proposal

Offit also criticised Kennedy’s initiative to expand research into vaccine injuries and improve reporting through the Vaccine Adverse Event Reporting System (VAERS).

Announced by the US Department of Health and Human Services in October, the initiative includes a new National Institutes of Health clinic, plans to record vaccine-related adverse events in electronic health records, modernisation of VAERS and a proposal to reimburse doctors for reporting suspected vaccine injuries.

When asked if the initiative was a useful step towards vaccine safety monitoring, Offit replied: “Not in his hands.”

He alleged that the information collected under the programme could be misrepresented to support claims linking vaccines to chronic diseases, including autism, diabetes and multiple sclerosis.

Offit also questioned whether the existing reporting system was being misunderstood. He said that "we did a pretty good job" establishing the existing vaccine injury reporting system.

He further described VAERS as a “noisy warning system”, explaining that reports can help identify adverse events but cannot establish that a vaccine caused a reported health problem.

The CDC says VAERS accepts reports of health problems after vaccination even when the person reporting them is unsure whether the vaccine caused the event.

Offit cited the example of the RotaShield rotavirus vaccine to illustrate how safety signals should be investigated. Reports of a possible serious adverse event prompted further study, which helped establish a link and led to the vaccine’s withdrawal.

His did not say that vaccine safety should go unexamined, but that reports must be investigated using reliable scientific methods.

When Andrea de Armas was diagnosed with breast cancer at 26, she was preparing for a future that looked very different from the one she was suddenly handed.

Along with surgery and chemotherapy, she had to make decisions about her fertility and adjust to the of long-term consequences from treatment.

Now 30 and cancer-free, the US woman is still taking hormone therapy. The treatment has put her into temporary menopause.

“I’m really lucky. I feel like I’m doing OK,” de Armas told CBS News. “It took me a little bit to kind of adjust. It wasn’t immediate; it took time. It took understanding the kind of changes my body was going through. But I’m able to live a pretty normal life for a 30-year-old.”

Andrea’s experience highlights a revealing challenge of breast cancer in younger women. Young women who survive breast cancer face a series of emotionally heavy decisions about menstrual cycles, fertility, sexual health and emotional well-being, and menopause that comes decades earlier than expected.

Effects Of Breast Cancer Treatment On Young Women

Also read: Why Peak Incidence For Breast Cancer In India Occurs Between Ages 40–50, Compared To 60–70 In The US & Europe

De Armas initially struggled to get her concerns taken seriously. She was eventually diagnosed with breast cancer in 2023 and discovered that she carried a genetic mutation associated with an increased risk of the disease.

She underwent a lumpectomy in June, followed by chemotherapy. She later had a bilateral mastectomy and reconstruction, scheduling treatment around her studies so she could continue her physician assistant programme.

“We worked together as a team,” said Dr. Cristina Lopez-Penalver, the surgical oncologist at Baptist Health's Herbert Wertheim Cancer Institute who treated her. “She was really not about ready to let this breast cancer get in her way.”

De Armas graduated as a physician assistant in 2025 and began working a month later. However, despite completing surgery and chemotherapy, she continues to take hormone therapy because of the characteristics of her cancer.

That medication has placed her in temporary menopause, a treatment-related effect that can be particularly difficult for younger women to navigate.

Early Menopause Due To Hormone Therapy

Also read: Breast Cancer: Know the Risks, Recognise the Signs & Get Checked

Menopause occurs when the ovaries stop releasing eggs and producing lower levels of hormones, particularly oestrogen.

Although natural menopause usually occurs in the late 40s or early 50s, some cancer treatments can bring on menopause much earlier.

According to the American College of Obstetricians and Gynecologists (ACOG), chemotherapy can damage the ovaries, causing periods to become irregular or stop altogether.

Hormone therapy can also block oestrogen's effects to help prevent hormone-sensitive breast cancer from returning.

Some women experience temporary ovarian suppression, in which medication switches off ovarian function during treatment.

Others may develop permanent ovarian damage and early menopause. The outcome depends on the treatment, the woman's age and her ovarian function before treatment. In de Armas' case, hormone therapy has brought on temporary menopause.

The transition can be more abrupt than natural menopause, leaving women with symptoms that affect daily life. Common effects include:

• Hot flashes and night sweats: Sudden waves of heat and sweating can disrupt sleep and daily activities.
• Sleep disturbances and mood changes: Hormonal changes may contribute to insomnia, irritability and low mood.
• Vaginal dryness and sexual discomfort: Reduced oestrogen can affect vaginal tissues and sexual health.
• Changes in fertility: Damage to ovarian function can reduce the chances of conceiving naturally, sometimes permanently.
• Bone health concerns: Low oestrogen levels can accelerate bone loss, increasing the risk of osteoporosis over time.

The National Cancer Institute notes that treatment-related ovarian insufficiency can also cause joint pain, reduced libido and difficulty concentrating.

Menopause is often characterised symptoms like by hot flashes and night sweats. But for some women, the transition can also bring changes in mood, memory and concentration that may be harder to identify. These symptoms can affect everyday life and may be misconstrued as stress, ageing or the emotional effects of children leaving home.

On World Menopause Day 2026, Dr. Abha Majumdar, gynaecologist and one of the lead IVF specialists in the country, told HealthandMe that women and their families need to identify the least obvious symptoms of perimenopause, the transition leading up to menopause.

Menopause Symptoms Dismissed For Empty Nest Syndrome

Empty nest syndrome refers to the feelings of grief, loneliness or loss of purpose that some parents experience when their children leave home to study, work or start their own families. The transition can bring changes to family routines and relationships, especially for parents who have spent years raising their children.

Dr Abha points out that mood changes in women during their 40s should not automatically be attributed to empty nest syndrome.

Perimenopause, the transition leading up to menopause, can also involve mood swings, forgetfulness and difficulty managing everyday tasks.

As she puts it, “Suddenly, around 45 or around that time, she starts feeling depressed. Everyone says, "Oh, children have grown up, you know, it is like an empty nest. But it is not just an empty nest.”

Recognising the symptom is key so that women experiencing new or persistent symptoms are not dismissed as simply struggling with their children leaving home, and can seek medical advice when needed.

Also read: World Menopause Day 2026: Perimenopause Can Begin In Your Late 30s. What Changes Should You Watch For?

Symptoms Not Related To Menstrual Cycle

Perimenopause can bring changes that don't relate to menstrual or hormonal cycle. Women may find themselves to be forgetful about routine things, struggle to concentrate or feel overwhelmed by tasks they previously managed with ease.

Dr Abha explains how these changes may appear in everyday life. She said, “She starts forgetting. She starts finding it difficult to cope with the daily chores which she did very easily before that.”

She says women may also face cognitive symptoms like brain fog and mood swings during this phase. She said, “Forgetfulness, cognition difficulties, brain fogging, mood swings.”

These symptoms can be confusing when women do not know that they come with menopausal transition. Changes in mood, for instance, may be misconstrued as reaction to family responsibilities, work stress or other pressures, while difficulties with memory and concentration may completely go unnoticed.

Also read: Menopause Abruptly Shifts Bones, Liver And Blood Fats, Study Finds

Perimenopause Duration

Perimenopause does not begin at the same age for everyone. Also, the transition may continue for several years before menopause sets in.

Dr Abha said that perimenopause may last for five or even 10 years before menopause sets in. She also said that fluctuating oestrogen levels are part of this phase.

“She's probably going through a perimenopause, which is it estrogen deprived and then comes up, goes down and comes up, and goes down and comes up. It may take couple of years for menopause to set in," she said.

Since the transition can be prolonged, understanding its symptoms is important for women as well as their families. Dr Abha explains that husbands and adult children should be attentive to changes in a woman's behaviour, mood or ability to manage familiar routines, rather than dismissing them.

She also stresses that women's health after menopause deserves attention, particularly as life expectancy increases.

She said, “Please support her at that time because she's got 25 years more to live right away. Maybe more.”

Medical Attention

Mood changes, fatigue, sweating and memory difficulties should not automatically be attributed to menopause. Other health issues can produce similar symptoms, which makes medical attention important.

Dr Abha advises women to seek help whenever they notice a change that makes everyday activities more difficult.

She said, “Any point. If she feels something is happening to her, she's not being able to cope with her daily chores. She used to cook so effortlessly, now it takes a lot of effort. She starts getting tired, she sweats. That is the time. May it be 40, may it be 45, may it be 38 also.”

A doctor can assess menstrual cycle and determine whether symptoms are related to perimenopause or another condition. Dr Abha says investigations may also help identify other possible explanations, including vitamin deficiencies or thyroid problems.

“So, they can be sorted out. So don't avoid going to a doctor if you feel something is changing in your body. And what you were coping with earlier, you're not being able to cope with that.”