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.

For a patient with advanced heart failure, there comes a point when medicines, devices and repeated hospitalisations can no longer control the disease. For some, a heart transplant may offer the only realistic path to long-term survival. Yet in India, the challenge often begins much earlier than the waiting list: many patients who could potentially benefit from transplantation never reach an advanced heart-failure or transplant centre for evaluation.

The scale of the problem is enormous. A recent study found that 83,000 heart transplantations were required annually in India in 2021, although only a very small proportion of that need was met. In comparison, according to the National Organ and Tissue Transplant Organisation (NOTTO), 221 heart transplants were performed in 2023.

Why Patients With Advanced Heart Failure Miss Out

The first issue is delayed referral. Patients with advanced heart failure may continue to be treated repeatedly for breathlessness, fluid retention or hospital admissions without being assessed early for advanced therapies.

A transplant evaluation is not a last-minute decision. It requires time to assess the patient's medical condition, other organs, infection risk, nutrition, psychosocial circumstances and ability to undergo lifelong follow-up.

The second challenge is the limited availability of donor hearts. Heart transplantation depends almost entirely on deceased organ donation. India has made substantial progress in transplantation overall, but the national deceased organ donation rate remains less than one donor per million population.

How Geography And Cost Affect Access To Transplants

Geography and affordability also matter. Advanced heart-failure programmes and transplant centres are concentrated in selected regions, meaning that patients from smaller cities and rural areas may face substantial travel, financial and logistical barriers.

The cost of evaluation, repeated hospitalisations, mechanical circulatory support and post-transplant medicines can further influence whether a patient can realistically pursue transplantation.

Also read: “You’ve Got A Pig’s Heart!” Genetically Modified Pigs with Human-like Organs Transforming Organ Donation; Details Inside

When Should Patients Be Referred To A Transplant Centre?

We therefore need to change the way advanced heart failure is recognised. A patient with recurrent hospitalisations, persistent symptoms despite optimal therapy, progressive kidney or liver dysfunction, low blood pressure limiting medications, or dependence on intravenous therapies should trigger consideration of referral to an advanced heart-failure centre.

Early referral gives specialists more time to evaluate the patient, assess treatment options and determine whether transplantation or another advanced therapy is appropriate.

Heart Transplant Is Not The Only Advanced Treatment

Importantly, transplantation is not the only advanced therapy. Left ventricular assist devices (LVADs) can serve as a bridge to transplantation or, in selected patients, as long-term therapy.

These devices can help support the heart's pumping function in patients with advanced heart failure who meet the criteria for their use. The appropriate option depends on the patient's condition, overall health and treatment goals.

India has demonstrated that transplantation can grow rapidly when infrastructure, coordination and public awareness improve. The next step is to ensure that patients are identified early enough to be evaluated, and that a shortage of donor organs does not remain the only reason they never get the opportunity to reach the transplant list.

By Dr. Pravin Kulkarni, MBBS, MS (General Surgery), MCh (Cardiovascular and Thoracic Surgery), Fellowship in CTS, Director, Advanced Cardiac Surgery and Heart and Lung Transplant Program

According to the latest National Family Health Survey (NFHS-6), 30.7% of women aged 15-49 years in India are reported as overweight or obese, highlighting the growing importance of lifestyle factors in women’s reproductive and overall health. Along with nutrition and physical activity, sleep is another important factor for overall menstrual health and the ovulation cycle.

Ovulation is controlled by a complex interaction between the brain, pituitary gland and ovaries. This reproductive hormone system is closely connected to the body's circadian rhythm, which regulates the sleep-wake cycle and influences the timing of several hormonal processes. When sleep becomes consistently irregular or insufficient, these signals may become disrupted, potentially affecting the hormonal coordination required for normal ovulation.

How Sleep Disturbances May Affect Reproductive Hormones

Also read: Andrew Huberman’s Sleep Trick: Can Eye Movements Help You Fall Back Asleep?

One of the ways this may occur is through interference with the functioning of the hypothalamic-pituitary-adrenal (HPA) axis. The reproductive system relies on communication between the hypothalamus and pituitary gland to regulate the hormones involved in follicle development and egg release.

Melatonin is another hormone linked to sleep and circadian rhythm. It also has antioxidant properties in the ovaries. This is why the relationship between sleep and fertility may involve more than simply the number of hours a woman sleeps.

A 2025 study published in Chronobiology International found that a later chronotype, or a tendency to sleep and wake later, was associated with a higher risk of sporadic anovulation among women with regular menstrual cycles.

Each one-hour increase in later chronotype was associated with a 5% higher relative risk of anovulation (RR 1.05; 95% CI 1.00–1.11), while women in the third chronotype tertile had a 33% higher relative risk compared with those in the second tertile (RR 1.33; 95% CI 1.05–1.68).

Interestingly, sleep duration itself was not associated with anovulation, suggesting that sleep timing and circadian patterns may also matter.

Poor Sleep Quality May Also Matter During IVF

Sleep may also be relevant during fertility treatment. A 2025 prospective cohort study of 174 women undergoing IVF/ICSI reported that women with poor sleep quality had 22.89% fewer retrieved oocytes and 22.01% fewer matured oocytes after adjustment for relevant factors.

The study also reported associations between certain sleep patterns and other IVF outcomes. However, these findings are observational and do not establish that poor sleep directly causes poorer fertility outcomes.

Breast cancer is often thought of as a disease that affects older women. However, younger women can develop breast cancer too, and receiving a diagnosis in your 20s or 30s can come as a shock, particularly when there is no known family history or obvious risk factor.

While breast cancer is less common at a younger age, being young should not mean dismissing a breast change. Here is what young women should know.

Being young doesn't mean a breast lump isn't worth investigating

Most breast lumps are benign, but a doctor should evaluate any new or persistent breast change. This includes a lump in the breast or under the arm, a change in breast size or shape, dimpling or puckering of the skin, changes in the appearance or position of the nipple, or unusual nipple discharge, especially discharge that is bloody.

Breast changes can occur because of hormonal fluctuations and several non-cancerous conditions, particularly in younger women. However, it is important not to assume that a change is harmless simply because of age.

Know your individual risk

Age is one of several factors that influence breast cancer risk. Having a close relative, such as a mother or sister, with breast or ovarian cancer can increase risk, particularly when the cancer occurred at a younger age. Certain inherited genetic changes, including BRCA1 and BRCA2 mutations, can also increase the risk of breast and ovarian cancers.

Previous radiation exposure to the chest at a young age is another recognised risk factor.

This is why knowing your family history matters. If breast or ovarian cancer has affected several close relatives, discuss your family history with a doctor. Depending on the pattern of cancers in the family, genetic counselling or testing may be recommended. Genetic testing, however, is not necessary for everyone and should be guided by an individual's risk profile.

Also read: ‘Feels Like I’m A Few Days From Death’: Olympic Sprinter Beth Dobbin Says She Is Bedbound 22 Hours A Day

Don't wait for a lump to become painful

Breast cancer does not always cause pain, and early-stage disease may not produce noticeable symptoms. At the same time, breast pain or tenderness and lumps can occur with several benign conditions.

In India, particularly across warmer and more humid regions, breast discomfort can also be aggravated by wearing very tight, heavy padded or underwired bras for prolonged periods. Such bras may cause pressure, friction and discomfort and can contribute to breast pain or mastalgia in some women, especially when the fit is not appropriate.

It is important to clarify that there is no scientific evidence that wearing tight, padded or underwired bras causes breast cancer. However, an uncomfortable or poorly fitting bra can contribute to breast discomfort. Choosing a well-fitted, supportive bra and avoiding prolonged pressure or friction may help reduce symptoms.

The important thing is to pay attention to changes that are new, unusual or persistent rather than trying to diagnose them yourself. Young women should be familiar with how their breasts normally look and feel so they can recognise when something has changed.

Also read: Dr Rachna Shroff: Indian-American Cancer Researcher Who Turned Her Diagnosis Into Advocacy

Screening should be based on risk, not age

Most women in their 20s and 30s who are at average risk do not need routine mammography screening. However, women with a higher-than-average risk may need to begin screening earlier and may require additional tests, such as breast MRI or mammography, depending on their individual circumstances.

Screening recommendations should therefore be based on personal and family history rather than age alone. Women who are concerned about their risk should discuss an appropriate screening plan with their doctor.

What can young women do?

Know your family history and share any significant concerns with your doctor. Maintain a healthy lifestyle by eating a balanced diet, exercising regularly, avoiding smoking and limiting alcohol consumption.

Most importantly, do not dismiss a breast change simply because you are young. Breast awareness is about understanding what is normal for you and recognising when something is different.

A breast lump or other change does not automatically mean cancer, but getting it checked can provide clarity and ensure that any condition requiring treatment is identified at the appropriate time. For young women, awareness is not about living in fear—it is about being informed, attentive and proactive about their health.

By Dr. Tapti Sen, Sr. Consultant - Breast Surgery, RG Hospitals, Kolkata