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.

When the name misleads, the disease remains misunderstood. Hence, endocrinologists now propose renaming PCOS as Polyendocrine Metabolic Ovarian Syndrome or PMOS.

This is because the term “Polycystic Ovarian Syndrome” is considered a misnomer. The name makes it sound like the condition is only related to the ovaries. However, over 30% of such patients have normal ovaries. The root lies in the hypothalamus, pituitary, adrenals, pancreas, and adipose tissue — truly polyendocrine.

The cysts in the name are actually antral follicles. The real burden is insulin resistance, dyslipidemia, NAFLD, and a 2-fold higher cardiovascular risk by age 50.

Not just reproductive: PCOS is India’s commonest endocrine disorder — 1 in 5 young women. It drives diabetes, hypertension, depression, and infertility.

PMOS, the acronym, expands as:

P — Polyendocrine: HPO axis + adrenal + insulin + leptin dysfunction

M — Metabolic: Insulin Resistance, obesity, fatty liver, CVD risk

O — Ovarian: Anovulation, hyperandrogenic ovarian dysfunction remains key

S — Syndrome: Heterogeneous, lifelong

This aligns with the 2023 International PCOS Guideline that defines it as a “metabolic + reproductive + psychological disorder”. Yet patients are still told, “You just have cysts.” PMOS reminds every physician to check OGTT, lipids, BP, and mental health at age 18, not 45.

The bottom line is that by changing the name, it is possible to change the game. When a 16-year-old hears “Polyendocrine Metabolic Ovarian Syndrome”, she understands it’s not vanity or infertility alone.

India is better prepared to deal with potential Hantavirus outbreaks due to the healthcare infrastructure and quarantine systems established during the COVID-19 pandemic, according to Dr NK Ganguly, former Director General of the Indian Council of Medical Research (ICMR).

In an exclusive interview with HealthandMe, Dr Ganguly said that while isolated cases of Hantavirus have appeared in India in the past, especially in crowded peri-urban and urban settings in Kerala, large-scale outbreaks have largely been reported in countries such as China, Argentina, the UK, and the US.

Dr Ganguly said that India's healthcare system significantly improved after the deadly COVID pandemic.

“India is overprepared in a way that during the COVID-19, our system, even at the district level or in much more rural settings, got established,” he said.

He pointed out that hospitals now have access to ECMO, BPAP systems, ventilators, and oxygen management facilities to curb the spread in case of an outbreak.

Dr Ganguly also mentioned the availability of antiviral drugs and experimental vaccine efforts that could potentially be explored for hantavirus treatment. “There are some crude vaccines which are made here also,” he said.

He added that India’s quarantine systems and public health drills developed during COVID-19 would also help contain future outbreaks.

“I think India will be okay because of the sheer transmission dynamics of this virus,” he said.

Hantavirus is a zoonotic disease that primarily gets transmitted through contact with infected rodents or exposure to their urine, droppings, and saliva, though rare cases of person-to-person transmission have also been reported.

According to the World Health Organization (WHO), 11 cases — including three deaths — have been confirmed so far. However, additional suspected and confirmed cases are likely to emerge across countries.

Also read: Hantavirus Can Linger Indoors, Spread Through Contaminated Dust, Says Infectious Disease Expert

Importance Of One Health

The One Health approach is critical in understanding and containing outbreaks like hantavirus, Dr Ganguly said.

The One Health approach, which integrates human health, animal health, and environmental monitoring, is also crucial to target the emerging infectious diseases, he noted.

Further, the noted microbiologist stressed the importance of strengthening surveillance across humans, animals, and the environment.

He explained that disease surveillance requires collaboration between bird specialists, forest experts, environmental scientists, and mammologists, especially for tracking zoonotic infections such as avian flu and hantavirus.

“In avian flu, birds follow special migration routes, so we needed bird specialists, forest experts, environmental experts, and mammologists,” Dr Ganguly said.

The expert also highlighted the growing challenge posed by shrinking spaces between humans and animals and the role of antimicrobial resistance (AMR) in emerging disease threats.

“Animal health is equally important. We need to maintain them, track their movements, and do surveillance,” he said.

Need To Track Climate

Dr Ganguly also warned that rising temperatures and shrinking boundaries between humans and animals could increase the risk of future infections.

“It is an environmental infection. With the rise of temperature, more hantavirus infections occur,” he told HealthandMe.

Why India Must Boost Surveillance

Calling surveillance one of the most critical tools in outbreak prevention, he urged India to strengthen monitoring systems for animals, vectors, and humans alike.

“We need to set up a dedicated surveillance for hantavirus in India, and we need to track hantavirus,” he said.

Dr Ganguly explained that to date, hantavirus cases in India have been detected accidentally during testing for respiratory infections or flu-like illnesses using advanced panel-based diagnostic systems.

“Like now these days, what happens is that when you are getting respiratory infection or flu-like symptoms, they put up a test system which is known as bio-fire or a thing like that which identifies 26 panels and gives the CT scoring of that, so from there, hantavirus emerged,” he said.

He added that India should strengthen surveillance tools and continue monitoring infections in animals, vectors, and humans alike.

Prateek Yadav (38), the son of late Samajwadi Party founder Mulayam Singh Yadav, died due to a massive blockage in the blood vessels of the lungs, leading to a collapse of the heart and respiratory system, as revealed in the postmortem examination report.

According to the autopsy findings, the provisional cause of death was recorded as “cardiorespiratory collapse due to massive pulmonary thromboembolism.” In simple terms, doctors said a large blood clot had blocked blood flow to the lungs, causing his heart and breathing to fail.

What Is Pulmonary Thromboembolism?

An embolism is any object (clot, fat, air, tissue) traveling through the bloodstream that becomes stuck, blocking blood flow. A thromboembolism is a specific type of embolism where that travelling object is a piece of a blood clot (thrombus) that has broken off from its original site.

It is a life-threatening condition that happens when a blood vessel in the lungs is blocked by a blood clot.

The common symptoms may include:

• Difficulty in breathing
• Chest pain
• Cough up blood

The blood clot starts in a deep vein in the leg and travels to the lung in most cases. Rarely, the clot forms in a vein in another part of the body, noted Mayo Clinic. When a blood clot forms in one or more of the deep veins in the body, it is called a deep vein thrombosis or DVT.

Other symptoms of pulmonary embolism include:

• irregular heartbeat
• lightheadedness or dizziness
• excessive sweating
• fever
• leg pain or swelling, usually in the back of the lower leg
• clammy or discolored skin

Also read: Your Desk Jobs May Impact Fertility, Not Just Waistlines, Say Experts

Lung Infection Claims Life of Karnataka Minister

Meanwhile, Karnataka's Planning and Statistics Minister, D. Sudhakar (66), passed away after a prolonged battle with a lung infection.

The most common lung infections that people experience are pneumonia, bronchitis, tuberculosis, influenza-related infections, and severe viral illnesses.

Experts noted that these lung infections cause fluid or pus to fill the air sacs, which prevents oxygen from entering the bloodstream.

"What may initially appear as a routine cough, fever, or chest infection can progress to severe pneumonia, respiratory failure, sepsis, or permanent lung damage,” Dr. Vikas Mittal, Director - Pulmonologist, CK Birla Hospital, Delhi, told HealthandMe.

Warning signs include

• worsening breathlessness,
• persistent fever,
• chest pain,
• bluish lips,
• confusion,
• falling oxygen levels should never be ignored.

Dr. Nikhil Rajvanshi, Consultant - Paediatric Pulmonology, Rainbow Hospital, Delhi, told HealthandMe that children may be more at risk of pulmonary infections as they can become dangerous quickly because their lungs and immune systems are still developing.

Common illnesses such as bronchiolitis, pneumonia, influenza, and other viral infections may rapidly lead to breathing difficulty, low oxygen levels, dehydration, and respiratory distress. Infants, premature babies, malnourished children, and those with asthma or congenital disorders are at higher risk of complications.

The experts called for

• early medical evaluation
• timely treatment
• vaccination
• good hygiene practices,
• quit smoking,
• maintaining immunity.