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.

Mumbaikars are currently being forced to wade through waterlogged streets, as the city has been receiving heavy rainfall for the last few days.

Floodwater often gets mixed with harmful contaminants like animal waste, animal feces, waste from human settlements, industrial pollutants, and harmful microorganisms, which can lead to serious monsoon infections.

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Here’s how one can stay safe after getting exposed to floodwater:

Precautionary Measures After Walking Through Floodwater

HealthandMe spoke to Dr. Murtaza S Bagwala, Head of Emergency Medical Services, Saifee Hospital, Mumbai, about how to keep infections at bay after coming in contact with filthy floodwater.

Pay Close Attention To Your Feet And Legs, Even If They Don't Hurt

When you are in floodwater, there may be sharp objects like broken glass, nails, stones and metal debris around you. You are more likely to come in contact with these objects unintentionally.

Dr. Bagwala recommends, “Small cuts, blisters, or punctures may not be noticed but can lead to infection if bacteria get into the skin. If you see any injury, clean it well, brush on antiseptics and consult a doctor for advice if the wound is deep or dirty.”

Also read: World Zoonoses Day 2026: Monsoon Season And The Rise Of Zoonotic Diseases

Don't Overlook Body Aches Or Fever In The Following Days

As the risk of contracting infections is high during monsoon, do not neglect if you develop flu-like symptoms after coming in contact with contaminated floodwater. The expert warns against dangerous monsoon infections like leptospirosis.

He says, “After contact with water contaminated with the urine of an infected animal (usually a rodent), the early symptoms of leptospirosis may include fever, severe muscle pain, headache, vomiting, chills, or redness of the eyes. The symptoms are very similar to those of a viral disease, so prompt medical evaluation is crucial to avoid complications, such as kidney, liver, or lung involvement.”

Don't Ignore Skin Changes

The doctor also says that if your skin’s colour or texture changes after getting exposed to floodwater, do not ignore it. He says that if the area around the feet or legs becomes red, swollen, painful, warm, discharges pus or the itching persists, it should be treated immediately.

These can be signs of bacterial or fungal infections that need to be treated, especially in individuals with diabetes, poor blood flow, or impaired immune function.

Also read: Leptospirosis In Monsoon: Expert Explains Why Early Detection & Prevention Is A Must

Determine If Your Tetanus Shots Are Updated

As you can get cuts and bruises after walking through floodwater, it is important to stay on top of your tetanus shots.

The expert advises, “Seek health care advice if you have a cut or puncture wound, particularly from a sharp object that was submerged in the water, while walking through the water. Early management of wounds can help avoid complications."

Take Precautions When Eating Or Drinking After Exposure

You are also at risk of contracting gastrointestinal infections after coming in contact with floodwater. Contaminated water may enter your mouth and lead to stomach and intestinal infections or may contact food and lead to food poisoning.

Prevent diarrhoea, vomiting and dehydration by drinking only clean, safe water, eating only freshly prepared food and practicing good hand hygiene before eating.

India has approximately 101 million people living with diabetes, one of the largest such populations in the world. Blood sugar levels, HbA1c targets, and medication compliance tend to dominate the clinical conversation around the condition. What receives considerably less attention, from both doctors and patients, is what diabetes does to the feet, and what the consequences of that neglect look like over time.

How Diabetic Foot Ulcers Develop

Diabetic foot ulcers develop when nerve damage caused by prolonged high blood sugar, referred to as diabetic neuropathy, reduces sensation in the feet. A small cut, blister, or pressure sore that a person without neuropathy would notice and address goes unfelt. In the absence of pain as a warning signal, the injury progresses. Infection sets in. By the time the patient presents for medical attention, the wound has often reached a stage where conservative management is no longer sufficient.

The High Cost of Delayed Treatment

The clinical outcomes associated with delayed presentation are sobering. A 2024 study published in Diabetes and Metabolic Syndrome, drawing on real-world data from a tertiary care facility in India, found that amputation was required in 43.4 percent of diabetic foot ulcer patients. Ten-year mortality among those who underwent amputation reached 30.9 percent, compared to 24.5 percent among those who achieved primary healing.

A 2025 cross-sectional study published in Cureus found a significant disparity in mortality rates between individuals with diabetic foot ulcers and those with diabetes alone, at 231 deaths per 1,000 person-years compared to 182. Globally, 18.6 million individuals develop diabetic foot ulcers annually.

Prevention Requires Daily Foot Care

The gap between the clinical evidence on diabetic foot complications and the attention the condition receives in routine diabetes management is where the preventable harm accumulates. Most patients presenting with advanced diabetic foot disease describe a history of minor symptoms that were attributed to something else, ignored, or left unaddressed because they were painless.

Regular foot inspection, appropriate footwear, avoidance of barefoot walking, and early medical review of even minor foot injuries are the practices that interrupt this progression before it reaches the point of irreversibility. Dedicated foot care clinics are built around exactly this philosophy, bringing together the multidisciplinary expertise needed to catch complications early and treat them before the window for limb salvage closes.

Why Multidisciplinary Care Matters

Eastern India carries a significant share of this burden, with patients across West Bengal, Bihar, Odisha, Jharkhand, and the Northeast frequently facing limited access to the multidisciplinary care that diabetic foot management requires. Diabetologists, vascular specialists, wound care experts, reconstructive surgeons, and rehabilitation teams working in coordination produce outcomes that sequential, single-specialty care cannot consistently achieve. Where such integrated care is available and accessed early, limb salvage rates improve, and amputations are reduced.

The Ministry of Health and Family Welfare’s recent advisory on diabetic foot care reinforces that foot health in diabetes management warrants systematic attention, not as an afterthought to glycemic control, but alongside it.

(Dr. Anupam Golash, Consultant - Plastic Reconstructive Surgery, CK Birla Hospitals, CMRI)

A small implanted device that stimulates the vagus nerve may offer substantial and lasting relief for people with severe treatment-resistant depression, according to a large multicenter clinical trial.

The findings, published in the International Journal of Neuropsychopharmacology, showed that improvements in depressive symptoms, quality of life, and daily functioning were sustained for at least two years in most patients who responded to treatment.

Notably, more than 20% of treated participants (39 patients) were in remission after two years, meaning their depressive symptoms had improved enough for them to function normally in daily life.

"We were shocked that one in five patients was effectively without depressive symptoms at the end of two years," said lead author Charles Conway, professor of psychiatry and director of Washington University's Treatment Resistant Mood Disorders Center.

Depression Remains A Major Health Burden

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Earlier this week, Republican Tom Kean Jr. revealed that he had been diagnosed with depression, explaining his absence from public life for more than 100 days.

He is far from alone. About 20% of U.S. adults experience major depression during their lifetime. While most people improve after antidepressants or psychotherapy, up to one-third develop treatment-resistant depression, in which standard treatments fail to provide adequate relief.

Study Focused on the Most Severe Cases

The RECOVER trial, led by researchers at Washington University School of Medicine in St. Louis, enrolled nearly 500 patients across 84 sites in the US. On average, participants had:

• Lived with depression for 29 years
• Tried 13 unsuccessful treatments
• Undergone therapies including electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS)
• Three-quarters were too ill to work.

"We believe the sample in this trial represents the sickest treatment-resistant depressed patient sample ever studied in a clinical trial," Conway said.

"There is a dire need to find effective treatments for these patients, who often have no other options. With this kind of chronic, disabling illness, even a partial response to treatment is life-altering, and with vagus nerve stimulation, we're seeing that benefit is lasting," he added.

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Benefits Lasted for Two Years

The VNS Therapy System, manufactured by LivaNova USA, Inc., involves implanting a small device beneath the skin of the chest. The device delivers carefully calibrated electrical pulses to the left vagus nerve, which serves as a major communication pathway between the brain and internal organs.

Although every participant received an implant, only half had their devices activated during the first year, allowing researchers to compare outcomes.

The latest analysis focused on 214 patients whose devices were activated from the beginning of the study.

Among them:

• About 69% (147 patients) achieved a meaningful improvement in at least one outcome after 12 months.
• More than 80% of those responders maintained or improved those benefits after 24 months.
• Among patients with a substantial response after one year, 92% continued to experience benefits two years later.

Conway noted that even a 30% improvement can dramatically change the lives of patients with severe depression, who often struggle to carry out basic daily activities and face a higher risk of hospitalization or early death.

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Some Patients Improved Later

The study also found that recovery may take longer for some people.

Nearly one-third of participants who had not responded after the first year reported meaningful improvements by the end of the second year, suggesting prolonged stimulation may continue to produce benefits.

Researchers also observed consistently low relapse rates among patients who improved, particularly among those with the strongest responses.