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.

Colorectal cancer (CRC), a term encompassing cancer of the colon and rectum, is not only a growing burden in India, but a significant proportion of patients are now being diagnosed at a young age. While colorectal cancer is more common in older adults, Indian clinical studies have identified the phenomenon of young onset colorectal cancer (YO-CRC), typically diagnosed before the age of 50. An experts’ review on epidemiology of colorectal cancer with special emphasis on India, an article in 2025 was published in the Indian Journal of Gastroenterology. The review found that there has been an annual rise of 2-3% in the incidence of colorectal cancer over the past two decades.

In the area of Young Onset Colorectal Cancer, an editorial in 2024 in the South Asian Journal of Cancer noted that one quarter to one-third of colorectal cancer patients in India were below 40 years, and many were diagnosed at stage III or IV. Titled Clinicopathologic Profile and Treatment Outcomes of Colorectal Cancer in Young Adults, A Multicenter Study from India, an article published in JCO Global Oncology studied colorectal cancer among adolescents and young adults. The study revealed 62.70% had colon cancer and 37.30% rectal cancer, with 67% being aged 30-39 years and no significant gender predisposition, though females had a higher metastatic burden.

Why is colorectal cancer affecting younger Indians?

There is no single explanation. Researchers have studied factors like dietary changes, obesity, physical inactivity, altered metabolism, alcohol consumption, smoking, and environment as possible contributors. Increasing urbanisation and changing food habits could also be playing a role in India’s shifting colorectal cancer profile. But not all patients present with conventional risk factors, and in many patients, the causes remain unclear.

Genetic predispositions need special mention. Conditions such as Lynch syndrome and familial adenomatous polyposis (an inherited genetic condition that causes precancerous polyps to form in the large intestine) can raise the risk of colorectal cancer at a young age, but most young-onset cases are not explained by an inherited cancer syndrome.

Also read: Pope Leo XIV, Diagnosed With Lung Cancer, Undergoes Surgery As His Brother Battles Relapsed Multiple Myeloma

The problem of missed symptoms

One of the biggest problems in cancer treatment is delayed diagnosis. Because cancer is associated with older age, the symptoms in younger people may be mistaken for piles, constipation, diet-related problems or even irritable bowel syndrome. Rectal bleeding, persistent changes in bowel habits, unexplained weight loss, abdominal pain, iron-deficiency anaemia, persistent fatigue, or a feeling of incomplete bowel evacuation is usually dismissed as minor issues in younger people.

What should young Indians do?

Colonoscopy is not a solution that can be recommended for every young adult. Symptoms- and risk-based screening is a more reasonable approach. People with persistent symptoms, a strong family history of colorectal cancer, hereditary cancer syndromes, inflammatory bowel disease, or unexplained anaemia may require more intensive evaluation (including colonoscopy) if clinically indicated. This are high risk group, and they need regular screening lifelong. India’s colorectal cancer burden is rising, and younger patients are important segment of this burden.

The evidence available does not prove a nationwide explosion of colorectal cancer in under-50 age groups in India, but it does demonstrate an increasing overall incidence, a significant presence of young onset colorectal cancer, and frequent late presentation. If someone have a first degree relative with colon or rectal cancer like parents, ideally, they should have a colonoscopy done by the age of 45. For younger Indians, early recognition of warning signs may be one of the most critical steps for timely diagnosis and improved outcomes.

By Dr. Abhishek Gangopadhyay, Consultant - Surgical Gastroenterology, Surgical Oncology, Narayana RN Tagore Hospital, Mukundapur, Kolkata

At 42, Danielle Ripley-Burgess of Kansas City, Missouri, has survived colon cancer three times, at 17, 25 and 39.

The disease often begins as noncancerous growths called polyps in the colon or rectum. Early-stage cancer and precancerous polyps may cause no noticeable symptoms. Ripley-Burgess spotted her first symptom at the age of 14 but ignored.

Her First Symptom At 14

At 14, Ripley-Burgess noticed specks of blood in her stool but hid them out of embarrassment, believing red foods might be responsible.

“I thought, I’m eating something red and that’s probably what I see,” she told Today. “So I put myself on a ‘no red foods diet’ and stopped eating anything that was red in color: everything from candy to pizza to salsa to raspberry popsicles.”

After two years she eventually told her mother, who believed it to be a case of hemorrhoids. As her bleeding worsened, and she developed fatigue and severe stomach pain, she was taken to a gastroenterologist.

Colon Cancer Diagnosis At Age 17 And 25

A few weeks after her 17th birthday, Ripley-Burgess was diagnosed with stage 3 colon cancer. She underwent chemotherapy, radiation and surgery. But years later, a follow-up colonoscopy revealed another cancerous polyp.

“I thought I had beaten cancer. I was getting colonoscopies every three years, and after one of them, I woke up and saw the very same look on the doctor’s face that I had seen eight years prior,” she said. “He saw a polyp that later turned out to be cancerous. I had no symptoms. At 25, I had stage 1 colon cancer.”

The second diagnosis was emotionally difficult as she feared losing the life she had built with her husband and the future they had planned.

Lynch Syndrome Increased Her Cancer Risk

Further testing revealed that Ripley-Burgess had Lynch syndrome, an inherited condition that increases the risk of colorectal, uterine and other cancers, according to the Mayo Clinic.

She underwent a preventive hysterectomy and subtotal colectomy, which removed all but about 13 inches of her colon.

Despite these measures, a colonoscopy in 2023 yet again detected a recurrence. At 39, she opted to have the remaining colon removed and a permanent ileostomy.

“I wasn’t expecting it, but I also wasn’t completely shocked,” she said, explaining that living with Lynch syndrome meant knowing cancer could return.

Why Blood in Stool Should Not Be Ignored

Ripley-Burgess now shares her story to encourage people, especially younger adults, to seek medical attention for unusual symptoms.

“If I could go back and tell my younger self something, it would be: Don’t be embarrassed about your body,” she told the outlet. “If you’re seeing something with your body that’s uncomfortable and weird, and you’re not ready yet to tell a doctor, tell somebody — a friend or family member. Don’t sit in that place of: something is wrong with your body, and you don’t know what it is. Don’t sit there alone. Don’t downplay what you’re seeing,” she

Colorectal cancer is expected to cause 158,850 new cases and 55,230 deaths in the US in 2026, according to the American Cancer Society.

Dr. Sajjan Rajpurohit, medical oncologist at BLK-Max Super Speciality Hospital, said, “Blood in the stool is one of the most common and concerning signs. While it might be due to hemorrhoids or fissures, it’s important not to assume. A proper evaluation is critical.”

Rectal bleeding can have several causes, but it should not automatically be attributed to hemorrhoids. Timely medical evaluation can help identify the cause and ensure appropriate treatment.

Six unvaccinated people, including children, have died from measles in the US this year. As of October 8, the country had reported 4,080 confirmed cases, according to the Centers for Disease Control and Prevention (CDC).

Measles spreads easily through the air and can remain infectious for up to two hours. Symptoms include high fever, cough, runny nose, red, watery eyes, and a rash that typically starts on the face. Infected people can spread the virus before the rash appears.

Two doses of the measles, mumps, and rubella (MMR) vaccine are approximately 97% effective against measles and remain the best protection against the disease and its complications.

Measles Can Cause Complications Years Later

Also read: Sixth Measles-Associated Death Reported In Pennsylvania As Cases Cross 1,100

Measles also causes pneumonia, brain inflammation, and death. Some complications emerge weeks or years after the initial infection.

Three serious consequences are acute disseminated encephalomyelitis (ADEM), immune amnesia, and subacute sclerosing panencephalitis (SSPE).

According to the CDC, one to three out of every 1,000 children with measles die from respiratory and neurological complications.

ADEM: When the Immune System Attacks the Brain

An 18-year-old from Mifflin County, Pennsylvania, died from acute disseminated encephalomyelitis (ADEM), reported as the state's fourth measles-associated death this year.

ADEM causes inflammation in the brain and spinal cord when the immune system mistakenly attacks nervous system tissue. It can develop weeks after infections such as measles or influenza.

Symptoms include weakness, confusion, vision problems, and seizures. Severe cases can be fatal.

ADEM occurs in approximately one out of every 1,000 measles cases. Treatment may include steroids, intravenous immunoglobulin, and plasma exchange.

Most patients recover, but lasting problems can include motor weakness, cognitive impairment, seizures, and vision loss. In a 2022 study of 77 children with moderate to severe ADEM, nearly a quarter had persistent health issues.

Immune Amnesia: Measles Can Erase Immune Memory

Read More: Measles Cases Are Rising in US—Who Should Get A Booster Shot?

Measles can destroy immune cells that remember previously encountered pathogens, weakening protection built through past infections and vaccinations. This is known as immune amnesia.

“Immune amnesia basically destroys your immune system,” said Dr. Stephen J. Elledge, professor of genetics and medicine at Harvard Medical School. “It infects and kills the cells that store immune memories — plasma cells, B cells, and T cells. It’s like burning down a library full of immunological knowledge.”

A 2019 study published in Science, co-authored by Elledge, found that measles could erase up to 73% of a person's antibody repertoire.

This loss can leave people vulnerable to infections their immune systems had previously learned to fight. Research published in 2015 suggested that rebuilding immune protection can take two to three years.

SSPE: A Fatal Disease That Can Emerge Years Later

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive neurological disease caused by a persistent measles virus infection in the central nervous system.

SSPE is "the most enigmatic and terrifying consequence of measles", Andrew Pavia, MD, a pediatric infectious disease epidemiologist at the University of Utah, told CIDRAP News.

Symptoms may appear seven to 10 years after measles, even in people who initially recover. Early signs include personality changes, mood swings, and headaches. The disease can progress to involuntary movements, seizures, vision loss, cognitive decline, coma, and death.

There is no known cure, and SSPE is ultimately fatal.

Infants Face a Higher SSPE Risk

Children who contract measles during infancy face a particularly high risk of SSPE.

The CDC estimated that seven to 11 out of every 100,000 people infected during the US measles resurgence of 1989–1991 were at risk of developing the disease.

A 2016 review of California health records estimated that SSPE occurred in approximately one out of every 609 children who contracted measles before 12 months of age.

A child in Los Angeles died of SSPE last year after contracting measles as an infant, before becoming eligible for the MMR vaccine. In the United States, the first dose is generally recommended at 12 to 15 months.

With measles cases continuing to rise, Pavia warned that SSPE "is a potential time bomb."