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.

Bruce Willis was diagnosed with frontotemporal dementia in 2022. His wife, Emma Heming Willis recalled the day when Bruce was diagnosed with the condition and how it made her feel "lost, isolated and afraid." Talkin to PEOPLE, Emma said, Bruce "never connected the dots" that he has been diagnosed with frontotemporal dementia. “I think that's like the blessing and the curse of this, is that he never connected the dots that he had this disease, and I'm really happy about that. I'm really happy that he doesn't know about it,” she shared about Bruce, 70.

Bruce Willis' Diagnosis

"On the day Bruce got his diagnosis, we walked out of the doctor's office with a pamphlet and an empty goodbye. No plan, no guidance, no hope, just shock," she explained in front of a packed auditorium, People reported.

In one instant, the family's future disappeared. The Oscar-winning actor, famous for his quick wit and performances in Die Hard and The Sixth Sense, would be leaving his career behind. Emma found herself thrust into a whole new role of full-time caregiver at the same time.

She continued to explain, "I found myself having to keep my family intact, raise our two small girls, and tend to the man that I love while dealing with an illness I hardly knew anything about."

Emma's emotional candor resonated with hundreds of families who have received similar diagnoses and encouraged her to author a book, The Unexpected Journey, scheduled for publication in September. In Emma's words, "This is the book I hope will assist the next caregiver. It is packed with encouragement, wisdom, and the encouragement necessary to walk this path.

Read: Bruce Willis’ Dementia Diagnosis Left Wife Emma Heming Feeling ‘Lost’ And ‘Isolated’ - What Are The Signs Of Caregivers Burnout?

What Is Frontotemporal Dementia?

Frontotemporal dementia is a less prevalent type of dementia that mainly occurs in the frontal and temporal lobes of the brain. It tends to affect behavior, personality, language, and movement more than memory, particularly in its initial stages.

In contrast to Alzheimer's, which generally strikes older individuals, FTD can hit at an earlier age—sometimes as young as 40. The symptoms can range from changes in personality, emotional flatness, or the inability to show empathy to impulsiveness, so it is especially hard for spouses and children to cope.

Emma's case illustrates how abrupt and disrupting this diagnosis can be—not only for the patient but for caregivers as well.

Whereas Bruce Willis' diagnosis hit global headlines, the mental toll taken by Emma, his caregiver, was largely in the background—until she decided to come forward.

Caregiving is a respectable position, but it's also a challenging and thankless one. For those who are caring for loved ones with dementia or other chronic illnesses, the stress of "keeping it all together" can result in a condition called caregiver burnout.

"Caring for someone is the most intimate and demanding work of love," Emma explained, "but when you're not noticed or supported, it begins to undermine your health—mentally and physically."

Work stress could make you gay, said a Malaysian minister Zulkifli Hasan, as continued government intervention of what is described as 'sexually deviant behavior' has pressured the country's LGBTQ community. This happened two weeks after religious authorities and police acted on complaints from a sultan and Islamist politicians that a camping retreat was promoting the LGBTQ lifestyle, reported South China Morning Post.

Religious Affairs Minister Hasan on Tuesday said that work stress could be among many other factors that is pushing people into sexual orientations other than heterosexuality. “Societal influence, sexual experiences, work stress and other personal factors come under this category [of possible causes],” Zulkifli said in a written parliamentary reply to a question by Siti Zailah Mohd Yusoff, a lawmaker with the opposition Islamist party PAS.

Also Read: Andy Kershaw Diagnosed With Spinal Cancer That Left Him Unable To Walk

He cited a 2017 study by Sulaiman et.al., that said such elements "can contribute to the increase in LGBT acts".

His comments have attracted a lot of backlash, with many people on social media mocking him. A social media user Muaz Zam said, "By this logic, I am genuinely shocked my entire office isn't gay by now". Another one read: "In other words: they never work hard in the parliament."

However, these claims are not scientifically back. Work related stress can impact a person, but cannot change their sexuality. It can, however, cause health effects. What it does not do is change one's sexuality and this is why one should know the difference about gender, sex and sexual orientation or sexuality.

'Work Stress Makes You Gay': The Difference Between Gender vs Sex

While these both terms are often used interchangeably in official forms, there is a difference between the two.

As per the Council of Europe, gender is an area that cuts across thinking about society, law, politics, and culture.

Read: Trump Administration Deadnames Transgender Former HHS Officer Rachel Levine in Official Portrait

Definition Of Gender vs Sex by WHO

The World Health Organization notes that sex refers to: "the different biological and physiological characteristics of males and females, such as reproductive organs, chromosomes, hormones, etc.”

Whereas, gender refers to: "the socially constructed characteristics of women and men – such as norms, roles and relationships of and between groups of women and men. It varies from society to society and can be changed. The concept of gender includes five important elements: relational, hierarchical, historical, contextual and institutional. While most people are born either male or female, they are taught appropriate norms and behaviours – including how they should interact with others of the same or opposite sex within households, communities and work places. When individuals or groups do not “fit” established gender norms they often face stigma, discriminatory practices or social exclusion – all of which adversely affect health."

Definition Of Gender vs Sex by The European Institute For Gender Equality

“Sex refers to the biological and physiological characteristics that define humans as female or male. These sets of biological characteristics are not mutually exclusive, as there are individuals who possess both, but these characteristics tend to differentiate humans as females or males.”

“Gender refers to the social attributes and opportunities associated with being female and male and to the relationships between women and men and girls and boys, as well as to the relations between women and those between men. These attributes, opportunities and relationships are socially constructed and are learned through socialisation processes. They are context- and time-specific, and changeable. Gender determines what is expected, allowed and valued in a woman or a man in a given context. In most societies, there are differences and inequalities between women and men in responsibilities assigned, activities undertaken, access to and control over resources, as well as decision-making opportunities. Gender is part of the broader sociocultural context. Other important criteria for sociocultural analysis include class, race, poverty level, ethnic group and age.”

The main difference is that gender is a social construct, whereas sex is the biologically labelled term based on organs and hormones.

Read More: Trump's Top Health Nominee Wants ‘Corrective Care’ For Trans People

What Is Sexuality?

As per the American Psychological Association (APA), sexuality is the capacity to derive pleasure from various forms of sexual activity and behavior. The Lanarkshire Sexual Health describes sexual orientation as a way to describe the feelings you have for someone you fancy or are attached to.

While sexuality can change overtime, it is not a choice. There is no evidence that sexual orientation can be forced to change through therapy.

Can Stress Impact Sexuality?

While stress can impact sexual function by reducing libido, causing fatigue, and triggering hormonal changes, it does not change one's sexual orientation. Jason Teoh, who writes on LGBTQ issues, project partner at NSW Department of Planning, Housing and Infrastructure, notes: "Sexual orientation is not caused by stress. It is not caused by trauma, influence or difficult life circumstances."

The WHO notes: sexual orientation is a natural, stable part of human identity shaped by biology, genetics, and early development. The WHO removed homosexuality from its disease classification in 1990. The American Psychiatric Association did the same in 1973.

Parkinson's disease is a progressive, neurodegenerative movement disorder caused by the loss of dopamine-producing brain cells, primarily affecting people over 60. Apart from motor loss, the disease also causes cognitive decline, depression, anxiety and swallowing problems.

The first symptom may be a barely noticeable tremor in just one hand or sometimes a foot or the jaw. Over time, swinging your arms may become difficult and your speech may become soft or slurred. The disorder also causes stiffness, slowing of movement and trouble with balance that raises the risk of falls.

However, before clear symptoms begin to appear, Neurologist Rachel Dolhun says certain signs may help identify the onset of the disease decades before it is diagnosed.

“It’s important to stress that not everyone who has these symptoms goes on to develop Parkinson’s,” said neurologist Rachel Dolhun. “But we know that in some people, these can be some of the earliest signs," she told The Washington Post.

Here is what you should look out for:

1. Loss Of Smell

Loss of smell, or hyposmia, is a common and early non-motor symptom of Parkinson's disease, affecting up to 90 percent of patients. This symptom can significantly impact quality of life by reducing the enjoyment of food and diminishing appetite.

While strongly linked to Parkinson's, smell loss can also stem from other causes, including sinus problems, COVID-19, or aging.

2. Acting Out Dreams

Acting out dreams, known as REM Sleep Behavior Disorder (RBD), involves physically enacting vivid, often unpleasant dreams through shouting, punching, or kicking during sleep.

This typically happens because the brainstem fails to temporarily paralyze muscles during REM sleep. It is a strong early warning sign of Parkinson's disease, often appearing years or decades before motor symptoms. About 50 percent of people with Parkinson's experience RBD.

READ MORE: Parkinson’s Patients May Soon Walk Better With This New Personalized Brain Therapy

3. Constipation

Constipation is a very common and significant non-motor symptom of Parkinson's disease that is caused by nerve changes slowing gut muscles and potentially exacerbated by low activity and dehydration.

Constipation can also be caused by Parkinson's medications such as anticholinergics, amantadine and other common drugs such as opioids, iron/calcium antacids.

4. Dizziness As You Stand

The autonomic nervous system fails to properly constrict blood vessels or increase heart rate upon standing, often due to a lack of norepinephrine. This causes the autonomic nervous system to fail in regulating blood pressure. Over time, this leads to Neurogenic Orthostatic Hypotension.

Beyond dizziness, symptoms include blurred vision, weakness, fatigue, cognitive "fog," and "coat hanger pain" (pain in the neck/shoulders). Often times, patients experience dizziness in the morning or immediately after meals.

Diagnosing Parkinson’s disease is mostly a clinical process, meaning it relies heavily on a healthcare provider examining your symptoms, asking questions and reviewing your medical history. Various imaging and diagnostic tests used to detect disease includes CT scan, PET scan, MRI scan and genetic testing.