Unintentional Weight Loss: When Rare Diseases Are the Hidden Cause

Unintentional weight loss is commonly alarming, particularly when it’s not explained by changes in diet, physical activity, or other known factors. It often leaves people confused and searching for answers. Although it can be related with gastrointestinal disorders, metabolic changes, infections, mental health, aging, and sometimes even cancer, this symptom can be  a silent sign of rare and frequently overlooked conditions.

When Is Losing Body Size Concerning?

If you’re experiencing a noticeable change in body size and don’t know why it´s happening, it can feel worrying and confusing. You are right to take it seriously. This specifically applies if it happens suddenly. This symptom may be a sign of an underlying medical issue, especially when it happens together with other unexplained ones.

Some warning signs include:

• Losing more than 10 pounds within a few months or more than 5 percent of your body weight within 6 to 12 months
• Feeling weak, dizzy, or chronically tired
• Ongoing digestive problems or changes in appetite
• Struggling with normal daily routines

If these symptoms are present and standard tests do not explain them, it may be time to look beyond common causes. In some cases, they could point to a rare or underdiagnosed condition that deserves further investigation.

Causes of Sudden Weight Loss

There are many reasons for a decrease in Body Mass. Some of the more common ones include:

• Gastrointestinal Disorders
• Thyroid problems, such as hyperthyroidism
• Type 1 or Type 2 diabetes
• Mental health issues, including depression and anxiety
• Chronic infections
• Certain cancers (BMJ 2024)

But what happens when these conditions are ruled out or the symptoms do not quite match? In these cases, rare diseases could be the key to understanding what is happening, as in many cases, this is one of the earliest symptoms to appear. Unfortunately, it is also one of the most easily overlooked or misattributed signs.

Below are examples of rare conditions where this change may be an important warning signal:

EGPA

EGPA is a rare autoimmune condition that causes inflammation of blood vessels. It often affects the lungs, skin, and nerves, but can also disrupt the digestive system. Many patients report a noticeable change in body size before they are diagnosed, especially when the gastrointestinal system is involved.

Fabry Disease

Fabry is an inherited metabolic disorder that leads to the buildup of a fatty substance in various organs, leading to neuropathic pain, stomach pain, diarrhea, and weightdrop, usually starting in childhood or early adulthood.

Gaucher Disease

Gaucher disease affects how the body breaks down certain types of fat. Symptoms may include an enlarged spleen, abdominal discomfort, fatigue, and gradual decrease in body mass, especially when the digestive system is under pressure. This will happen more frequently in untreated patients, especially in childhood.

HAE

HAE is known for its unpredictable swelling attacks. When these affect the digestive tract, they can cause nausea, vomiting, abdominal pain and diarrhea, which can lead to reduced appetite and losing body size over time.

MPS I

MPS I is a rare genetic disorder caused by the deficiency of an enzyme needed to break down certain complex sugars. It can lead to a buildup of substances in cells, resulting in growth delays, organ enlargement, and malnutrition. Children with MPS I may begin to show signs such as a visible reduction in physical build, joint stiffness, and respiratory problems early in life.

Hunter Syndrome (MPS II)

Hunter syndrome primarily affects boys and causes a wide range of symptoms, including developmental delays, digestive issues, and progressive thinning. Feeding difficulties and chronic gastrointestinal symptoms can make it hard for children with MPS II to maintain a healthy weight, especially in the later stages of the disease.

Morquio syndrome (MPS IV)

In Morquio syndrome, the body is unable to break down specific molecules that help build connective tissue. This leads to skeletal abnormalities and growth failure. Children with MPS IV commonly experience poor nutrient absorption, which can result in malnutrition and gradual decrease in body mass, even if their appetite is not concerning.

PNH

PNH is a rare blood disorder that leads to the destruction of red blood cells. The most characteristic syndrome is dark urine, especially in the morning. It can also result in anemia leading to chronic fatigue, abdominal pain, and sudden loss of body size, even before the more well-known symptoms become obvious as mentioned by Fields (2024).

ATTR Amyloidosis

In ATTR amyloidosis, a misfolded protein builds up in tissues and organs. The Amyloidosis Foundation noted that one of the first signs can be rapid and unexplained weight loss, which is oftentimes accompanied by numbness, heart issues, or swelling.

Why Rare Diseases Are Often Missed

Because rare diseases affect fewer people, they are not always top of mind for healthcare providers. Many patients with rare conditions face:

• Delayed diagnoses, often for years
• Multiple misdiagnoses
• Treatments that do not address the real issue

Recognizing that unwanted weight loss can be an early sign of a rare disease helps patients and their families ask better questions and seek specialist input sooner.

Take the Next Step Toward Clarity

If you experience unexplained weight loss or other symptoms that might be linked to rare diseases, do not wait.

Just fill out our Patient Form, and we’ll analyze your case with the help of medical experts and AI-supported tools.

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Frequently Asked Questions

Why am I losing weight unintentionally?

Unintentional decrease of body mass can be caused by a variety of factors including infections, stress, thyroid disorders, and in some cases, rare diseases like EGPA or Fabry. If no clear cause is found, it may be time to look deeper.

What autoimmune disease causes weight loss?

Several autoimmune diseases can cause progressive thinning. In rare cases, EGPA or related vasculitides may lead to weight loss due to inflammation and organ involvement. Others include celiac disease, Lupus, or Crohn’s disease.

What is considered unhealthy rapid weight loss?

Losing more than 1 to 2 pounds per week without trying is typically considered concerning. If this is happening to you, especially with other unexplained symptoms, medical attention is strongly recommended.

Sources: 

• Mayo Clinic. (n.d.). Unexplained weight loss: When to worry. 
• BMJ. (2024). Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study (update)  . BMJ, 370, m2651.
• NIH Genetic and Rare Diseases Information Center (GARD). (n.d.). Eosinophilic granulomatosis with polyangiitis. 
• National Fabry Disease Foundation. (n.d.). What Is Fabry Disease?. 
• Kałużna, M., Trzeciak, I., Ziemnicka, K. et al (2019). Endocrine and metabolic disorders in patients with Gaucher disease type 1: a review. Orphanet J Rare Dis 14, 275 (2019). 
• HAEi. (n.d.). Symptoms of Hereditary Angioedema (HAE). 
• Orphanet. (n.d.). Mucopolysaccharidosis type I / II / IV. 
• Fields, L. (2024). Getting to Know PNH Warning Signs.
• Amyloidosis Foundation. (n.d.). Hereditary ATTR Amyloidosis.