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.

Vaccinated for human papillomavirus (HPV)? Now, take that Pap smear test. This is the most common advice women hear to prevent the risk of cervical cancer that annually causes around 6,60,000 new cases and around 350,000 deaths worldwide.

However, it's easier said than done for most of the fairer sex.

A Pap smear is typically a gynecological examination where a speculum is inserted to collect cells from the cervix.

Although the procedure is brief and generally safe, the discomfort discourages many from getting screened. Fear of pain, anxiety of the results, form the common psychological barriers worldwide, and is followed by shame, cultural attitudes, and concerns with male clinicians.

A study in Iran, published in the BMJ Open journal in January 2024, showed that psychological stress, cultural issues, and fear, along with limited information and health services, were the biggest hindrances to getting Pap tests.

Another research published in the BMC Women's Health in December 2022, focusing on Africa, Asia, and South America, reported that many women avoided or delayed Pap smears because they are afraid the procedure will hurt. Many also reported being embarrassed about the pelvic exam or fear of having a stranger see their private areas. Some also worried that the test could damage the uterus.

A Pap Smear test, however, is proven to be safe and is recommended for every woman above the age of 21 years.

“A Pap smear is a rapid, safe, and painless screening procedure that detects irregular cellular changes well before they become malignant. The ability to treat at this pre-cancerous stage of disease provides an excellent outcome,” Dr. Tirathram Kaushik, Senior Consultant GI, HPB, Gastrointestinal & Thoracic Oncology and Robotic Surgery, HCG Cancer Centre, Borivali, told HealthandMe.

A 2025 study, published in the Journal of Contemporary Clinical Practice, showed that pap smears are excellent at ruling out precancerous risks. It also remains a valuable screening tool where molecular testing is limited.

There are many myths about Pap smears that make people anxious or avoid screening. Let’s clear up the most common ones:

Pap Smears Are Painful

The Pap smear procedure, which takes only a few minutes, is often described as uncomfortable. While some feel like a quick pinch, others experience slight discomfort or spotting. Severe pain is not considered normal.

“From an oncology perspective, this myth results in a delay in diagnosis. Cervical cancer often occurs silently in its early stages, without any noticeable symptoms,” Kaushik said.

I Am Healthy, So I don’t need A Pap Smear

While individuals may feel completely well, they still have abnormal cells developing silently. As a result, regular Pap smear screening is important because it detects these changes early -- before they turn into cervical cancer.

“The HPV infection and subsequent changes that lead to cervical cancer happen slowly over many years. HPV infection is also very common, and one in two women is likely to get infected. Regular screening by a Pap smear will help to catch infection early before it can convert into cancer,” Dr. Deepak Jha, Chief - Breast Surgery & Sr. Consultant Surgical Oncology, Artemis Hospitals, told HealthandMe.

I Have Only One Partner, So I don’t need Screening

“HPV doesn’t need penetrative sex for infection. It can be transferred if there is any contact of bodily fluid. It’s always safe to test and be assured rather than repent later,” Dr. Jha said.

Testing Means Cervical Cancer

“Even if HPV is detected, it usually indicates a pre-cancerous stage that is highly treatable,” Dr. Parminder Kaur, Consultant Gynecologic Oncologist at CK Birla Hospital, Delhi, told HealthandMe.

Moreover, a Pap smear only screens for cervical cancer; it can’t detect other gynecological cancers such as cervical, ovarian, uterine (endometrial), vaginal, and vulvar cancers. So, screening and appropriate tests for those will be required, irrespective of the Pap smear.

I Am old, So I don’t need A Pap Smear

I Got Vaccinated, So I Do Not Need A Pap Smear

Irrespective of vaccinated status, a woman should go for regular screening between the ages of 25 and 79. Also, if a woman already had HPV exposure before being vaccinated, she would not benefit, the experts said.

“Screening is not just a routine procedure - it is a preventive measure. In the treatment of cancer, early detection alters the disease course, whereas waiting for symptoms to develop means the disease is likely to be already advanced,” Dr. Kaushik said.

Dr Kaur called for more awareness and stated that open discussion are key to help more women take the important screening test.

When To Get Screened

The United States Preventive Services Task Force (USPSTF) and the American Cancer Society (ACS) recommend getting your first Pap test at age 21, followed by Pap testing every 3 years. Even if you are sexually active, you do not need a Pap test before age 21.

• Individuals must start getting Pap tests at age 21. If the result is normal, repeat the test after three years.
• For individuals aged between 30 and 65 years old, doctors are likely to recommend an HPV test along with a Pap test. If both are normal, repeat after five years.

In women older than 65, you don't need to be screened anymore if:

• You have had at least three Pap tests or two HPV tests in the past 10 years, and the test results were normal or negative, and
• You have not had a cervical precancer in the past, or
• You have had your cervix removed as part of a total hysterectomy for non-cancerous conditions, like fibroids.

Are you still experiencing brain fog, fatigue, and mood changes even after years of a mild COVID-19 infection? A new study showed that the SARS-CoV-2 virus, behind the COVID infection, can cause persistent brain inflammation and lung injury, according to a study.

Researchers from Tulane University, in Louisiana, US found that the brain inflammation lasts long even after the virus was no longer detectable.

Their study, published in Frontiers in Immunology, can answer why long COVID often includes neurological symptoms such as brain fog, fatigue, and mood changes.

"Long-term effects on the brain were unique to SARS-CoV-2. That distinction is critical to understanding long COVID," said lead author Dr. Xuebin Qin, professor of microbiology and immunology at the Tulane National Biomedical Research Center. Qin also mentioned "lasting lung injury" among COVID patients.

In a mouse model, the team found that immune cells in the lungs failed to fully stand down and also spiked the buildup of collagen -- a protein associated with scarring.

The changes stiffened lung tissue, making breathing feel more labored -- a possible answer to breathlessness faced by COVID survivors.

Further, the researchers also noted no repair to the injury, suggesting the virus may interfere with the lung's natural healing process.

On the other hand, in the brain, the mice with COVID showed signs of persistent brain inflammation weeks later. The team also reported tiny areas of bleeding.

Conducting a gene expression analysis, the team found ongoing inflammatory signaling and disruption of pathways involved in serotonin and dopamine regulation -- brain functions linked to mood, cognition, and energy levels.

What Is Long COVID?

Long COVID is a collection of symptoms that last three months or longer after your first COVID symptoms. They include fatigue, brain fog, headaches, breathlessness, altered sense of smell or taste, headaches, and more.

While many of the Long conditions remain to be fully recognized, some people have more than one symptom.

mRNA Vaccine Against COVID

As per recent data from the World Health Organization, more than 43,000 new cases have been reported from 61 countries, between January and February.

Vaccination that prevents SARS-CoV-2 infection is the most effective way to prevent long COVID.

Recently, the European Medicines Agency (EMA) recommended a marketing authorisation in the European Union (EU) for mCombriax -- a messenger RNA vaccine for protecting people aged 50 years and older against COVID-19 and seasonal influenza (flu).

Co-infection with the influenza virus and SARS-CoV-2 can result in more severe disease than would occur with either SARS-CoV-2 or influenza virus infection alone.

mCombriax works like other vaccines by preparing the body to defend itself against infection. It contains messenger RNA with instructions for making proteins found on SARS-CoV-2 and the following seasonal influenza viruses: influenza type A-H1N1, influenza type A-H3N2, and influenza type B of the Victoria lineage.

Vitamin B12 might sound like just another nutrient on a health label but it plays a major role in how your body works. The vitamin is crucial in helping the body produce red blood cells, supports your nervous system and essential for making DNA, which is the genetic material inside all your cells.

Symptoms of a Vitamin B12 deficiency often appear slowly. You may not notice them at first, or may blame them on stress, lack of sleep or a busy schedule. However, if this deficiency continues for too long, it could lead to serious health problems.

Here are three key signs to look out for:

1. Ongoing Fatigue and Weakness

Vitamin B12 is extremely crucial for making red blood cells who are responsible for carrying oxygen from your lungs to the rest of your body. Oxygen is what your cells need to produce energy.

Without adequate levels of B12, the body cannot produce enough healthy red blood cells, leading to a condition called anemia.

This can make you feel constantly exhausted, even after getting enough sleep. You may also feel weak, short of breath or find that everyday tasks feel harder to do than they generally are.

If the fatigue feels persistent and does not improve with rest, it is important to seek a consultation with a doctor.

2. Tingling or Numbness in the Hands and Feet

Vitamin B12 is also essential for maintaining the myelin sheath, a protective covering around your nerves. You can think of it like the protective plastic that we see around electrical wires. It helps nerve signals travel quickly and correctly between your brain and the rest of your body.

When B12 levels are too low, this protective layer can become damaged and subsequently lead to nerve signals slowing down or misfiring. This may lead you to feel pins and needles, tingling or numbness in your hands and feet. Some people also experience burning sensations or difficulty with balance.

At first, it may seem minor, such as your foot ‘falling asleep’. But if these sensations happen often or without a clear reason, they should not be ignored. Long-term B12 deficiency can cause permanent nerve damage, which is why early medical consultations are important.

3. Brain Fog, Memory Problems or Mood Changes

Your brain also depends on vitamin B12. It helps your body produce neurotransmitters, which are chemicals that allow brain cells to communicate with each other. These chemicals influence memory, focus and mood.

When B12 levels are low, communication between brain cells may not work as efficiently. You may notice difficulty concentrating, forgetfulness or a feeling of mental fog. Some people feel more irritable, anxious or unusually low in mood.

As these symptoms are common during stressful times, they are often dismissed. However, if you feel mentally different from your usual self for a long period, it is important to investigate the cause.

Why Does B12 Deficiency Happen?

Vitamin B12 is mainly found in animal-based foods such as meat, fish, eggs and dairy products. People who follow vegetarian or vegan diets may need fortified foods or supplements to get enough.

Absorption is also a key factor. Vitamin B12 needs a special protein in the stomach called intrinsic factor to be absorbed properly. Certain medical conditions, medications, or aging can reduce absorption. This means that even if someone eats enough B12, their body may not absorb it efficiently.

When to See a Doctor

If you experience ongoing fatigue, tingling sensations or noticeable changes in memory or mood, consult a healthcare professional. A simple blood test can measure your B12 levels.

The good news is that Vitamin B12 deficiency is usually treatable. Treatment may include dietary changes, oral supplements or, in more severe cases, injections. When identified early, most people recover well.

The Bottom Line

Vitamin B12 supports your blood, nerves and brain. A deficiency can quietly affect your energy, sensation and thinking over time.

Pay attention to persistent changes in your body. If something feels consistently wrong, it is important to seek medical advice. Early detection can prevent long-term complications and help restore your health.