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.

While GLP-1 weight-loss drugs such as Wegovy and Mounjaro have helped patients lose weight, a major concern has been weight regain once the therapy is stopped. Now, a new study by US scientists suggests that a daily pill may help prevent that rebound weight gain.

According to a clinical trial led by Weill Cornell Medicine and NewYork-Presbyterian, switching to the once-daily orforglipron pill may not only help maintain weight loss but also preserve cardiometabolic benefits.

Orforglipron is US drugmaker Eli Lilly’s first oral pill for weight loss, marketed as Foundayo. In April, it received approval from the US Food and Drug Administration (FDA).

Weight Loss With Daily Pill Orforglipron

In the Eli Lilly-funded trial, published in the journal Nature Medicine, researchers found that patients in the Phase 3b clinical trial maintained around 75–80 per cent of their weight loss. They also experienced several additional health benefits, including:

• Reduced waist circumference
• Improved blood pressure
• Better blood sugar control
• Lower triglyceride levels
• Improved cholesterol levels

The Clinical Trial

The ATTAIN-MAINTAIN trial enrolled patients who had already achieved substantial weight loss that later plateaued while taking weekly injectable GLP-1 drugs during the SURMOUNT-5 trial.

The study randomized:

• 205 patients taking tirzepatide
• 171 patients taking semaglutide

The results showed that patients switching from tirzepatide to orforglipron maintained an average of 74.7 per cent of their body weight reduction, compared with 49.2 per cent in the placebo group.

Meanwhile, patients who switched from semaglutide to orforglipron maintained 79.3 per cent of their body weight reduction, compared with 37.6 per cent in the placebo arm.

Over the 52-week trial period, participants treated with orforglipron gained:

• An average of 5 kg (11 lbs) in the tirzepatide group
• An average of 1 kg (2.2 lbs) in the semaglutide group

How The Daily Pill Orforglipron Works

Eli Lilly licensed orforglipron, the active ingredient in Foundayo, from a Japanese pharmaceutical company in 2018.

Like injectable GLP-1 drugs, Orforglipron is available in six doses ranging from 0.8 mg to 17.2 mg. Patients typically begin at the lowest dose and gradually increase under medical supervision.

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Unlike some oral GLP-1 drugs, people taking orforglipron do not need to restrict food or drink intake after taking the pill. Researchers say the small molecule is absorbed quickly into the bloodstream and reaches target tissues efficiently.

Orforglipron: Side Effects And Safety Concerns

Foundayo is not approved for use in children and carries warnings about potential thyroid tumours, including thyroid cancer.

The drugmaker advises patients to watch for symptoms such as:

• Lump or swelling in the neck
• Hoarseness
• Trouble swallowing
• Shortness of breath

• Nausea
• Constipation
• Diarrhoea
• Vomiting
• Indigestion
• Stomach pain
• Headache
• Swollen belly
• Fatigue
• Belching
• Heartburn
• Gas
• Hair loss.

In a major development for cancer care in India, Swiss pharmaceutical major Roche Pharma has launched Tecentriq SC, the country’s first subcutaneous (under-the-skin) immunotherapy for lung cancer that can be administered in approximately seven minutes.

While conventional intravenous (IV) infusions can take hours, Tecentriq SC can significantly improve the cancer treatment experience by reducing treatment time by nearly 80 per cent.

The seven-minute injectable immunotherapy has the potential to:

• Treat up to five patients in the time taken to treat one patient through intravenous infusion
• Help optimise healthcare resources
• Lower indirect treatment costs
• Minimise the need for patients to travel long distances
• Reduce the amount of time caregivers spend in hospitals

“With Tecentriq SC, we are bringing an innovation that meaningfully reduces treatment time while maintaining the established efficacy and safety profile of Tecentriq. We believe such advances can play an important role in enabling more patient-centric and future-ready cancer care delivery in India,” said Roche Pharma India Chief Medical Officer Dr Sivabalan Sivanesan, in a statement.

What Is Tecentriq SC? What's The Cost In India?

Tecentriq SC is the first and only PD-(L)1 inhibitor globally with both intravenous (IV) and subcutaneous (SC) formulations across multiple cancers.

First approved by the UK MHRA in 2023 and subsequently by the USFDA in 2024, Tecentriq SC is now approved in more than 85 countries, with over 10,000 patients benefitting globally.

In India, Tecentriq SC is currently approved by the DCGI for adjuvant and metastatic non-small cell lung cancer (NSCLC). NSCLC is the most common form, making up about 80–85% of all cases.

According to Sivanesan, the drug is priced at about "Rs 3.7 lakh per vial".

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How Does Tecentriq SC Work?

Tecentriq SC combines Tecentriq with Halozyme Therapeutics’ Enhanze drug delivery technology.

The technology uses recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily increases permeability in the subcutaneous space, enabling rapid dispersion and absorption of the medicine into the bloodstream, the company said.

How Tecentriq SC will Boost Cancer Care In India

The launch of Tecentriq SC also aligns with the broader shift toward decentralised cancer care in India. Shorter administration formats can free up hospital beds, healthcare staff time, and oncology resources at tertiary care centres, while helping shift care delivery to daycare centres and beyond traditional tertiary hospitals.

“India’s growing cancer burden requires us to rethink how cancer care is delivered. Innovations such as subcutaneous immunotherapy have the potential to simplify treatment administration, reduce pressure on hospital beds and support more decentralised models of care beyond large metro hospitals,” said Dr Amit Rauthan, Consultant and HOD of Medical Oncology at Manipal Hospital.

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Tecentriq SC: Safety

Global studies have indicated strong patient preference for subcutaneous administration.

According to results from the IMscin002 study presented at the European Lung Cancer Congress (ELCC) 2024:

• Four out of five patients preferred Tecentriq SC over IV administration
• Patients cited less time in clinics, greater comfort, and lower emotional distress as key reasons for preference

Studies have also shown that subcutaneous administration is associated with less discomfort, pain, and irritation compared to IV administration.

In the IMscin001 study presented at ESMO 2023:

• 90 per cent of healthcare professionals agreed the SC formulation was easy to administer
• 75 per cent believed it could save time for healthcare teams.

Even as Polycystic Ovary Syndrome (PCOS) got rebranded as Polyendocrine Metabolic Ovarian Syndrome (PMOS), it signals a major shift in how doctors understand and treat one of the most common hormonal conditions affecting women, said health experts today.

Speaking to HealthandMe, the experts noted that from the earlier narrowed focus on ovarian cysts, the transition toward PMOS will better capture the condition’s complex metabolic and endocrine nature.

Dr. Isha Kriplani, Consultant – Obstetrics and Gynecology at Paras Health, said the renaming marks “the beginning of a new era in women's gynecological health.”

What Does PMOS Mean?

Also read: PCOS Is Now PMOS: What The Name Change Means For Millions Of Women

The new name aims to explain the condition more accurately and comprehensively.

Polyendocrine means it affects multiple hormones in the body.

Metabolic refers to issues linked to weight, insulin, blood sugar, and heart health.

Ovarian highlights its impact on ovulation and reproductive health.

Syndrome refers to a group of symptoms occurring together.

In simple terms, PMOS is a hormonal and metabolic condition that can affect periods, fertility, skin, mood, weight, and long-term health.

How Will The Change Impact Women

Dr. Isha stated that the term PMOS acknowledges that the disorder is not solely linked to hormonal imbalance or ovarian dysfunction, but also deeply connected to metabolic health. She explained that many women experience symptoms such as weight gain, skin issues, fatigue, insulin resistance, and hormonal disturbances without necessarily showing ovarian cysts on ultrasonography.

“Rebranding Polycystic Ovary Syndrome (PCOS) into Polyendocrine Metabolic Ovarian Syndrome (PMOS) is the beginning of a new era in women's gynecological health. This is because renaming helps us understand that the complex interplay of this disease is not only about imbalanced hormones but also metabolism,” she told HealthandMe.

Dr. Isha added that the shift could help broaden diagnosis and encourage early intervention to prevent long-term complications such as type 2 diabetes and hypertension. She noted that the new terminology also provides women with a more accurate understanding of the syndrome and encourages treatment strategies focused on addressing the root metabolic causes.

Why The Change To PMOS Was Necessary

Dr. Raina Chawla, Associate Director – Gynecology at Sarvodaya Hospital, told HealthandMe the transition from PCOS to PMOS corrects what she described as one of medicine’s “most persistent misnomers.”

She explained that for years, the term PCOS led many patients to believe the condition was purely ovarian in nature, often resulting in confusion and delays in diagnosis. According to Dr. Raina, the so-called “cysts” seen in PCOS are actually immature follicles that develop as a consequence of the disorder rather than being its primary cause.

Also read: PCOD vs PCOS vs PMOS: Why The Condition’s Name Has Changed Over Time

“The shift from PCOS to Reproductive Metabolic Syndrome (PMOS) is an important move toward correcting one of medicine’s most persistent misnomers,” Dr. Raina said.

She further emphasized that the newer terminology places appropriate attention on insulin resistance and androgen excess, helping doctors and patients approach the disorder as a systemic endocrine and metabolic condition rather than a localized ovarian issue.

Experts believe the change in terminology could also reduce stigma and improve awareness about the wide-ranging symptoms associated with the syndrome, while encouraging a more holistic treatment approach that includes lifestyle modifications, metabolic screening, and long-term preventive care.