Chronic Dyspepsia

Chronic dyspepsia is defined as persistent or recurrent upper abdominal discomfort lasting for more than three months, often resistant to standard treatment. In addition, patients may experience bloating, early satiety, and nausea.

Although dyspepsia is usually related to gastritis or gastroesophageal reflux, it may also suggest a deeper systemic or metabolic cause, including rare diseases.

Metabolic and Lysosomal Storage Diseases

In many rare metabolic disorders, chronic dyspepsia stems from impaired motility, enzyme deficiency, or organomegaly. For example:

Fabry Disease 

Chronic dyspepsia is one of the most common early symptoms. Patients frequently report abdominal pain after eating, bloating, diarrhea, or early satiety due to autonomic neuropathy and small vessel involvement.

Gaucher Disease

Chronic epigastric fullness or dyspepsia can occur due to splenomegaly and hepatomegaly, leading to compression of abdominal organs and altered digestion.

Lysosomal Acid Lipase Deficiency (LAL-D)

Fat accumulation in the liver and intestines may cause persistent epigastric discomfort, mimicking chronic dyspepsia.

Pompe Disease

Smooth muscle involvement and respiratory weakness can impair gastrointestinal motility, leading to long-term dyspeptic symptoms.

Autoimmune and Inflammatory Rare Diseases

The symptom can also appear in systemic inflammatory or autoimmune conditions where the gut lining or immune mediators are affected:

Systemic Mastocytosis

Persistent dyspepsia and reflux are frequent due to histamine release and gastric acid hypersecretion. Some patients may also experience nausea and cramping.

Eosinophilic Gastroenteritis

This rare inflammatory disease presents with chronic dyspepsia, early satiety, and abdominal pain, caused by eosinophilic infiltration in the stomach and intestines.

Hereditary Angioedema (HAE)

Recurrent abdominal swelling episodes may simulate chronic dyspepsia, though symptoms occur episodically. Between attacks, some patients report persistent mild discomfort.

Hematological and Oncologic Rare Diseases

In rare hematologic or oncologic conditions, chronic dyspepsia can result from chronic inflammation, cytokine release, or organ involvement:

Systemic Amyloidosis

Amyloid deposits in gastric tissue impair motility and digestion, causing long-lasting dyspeptic symptoms.

Castleman Disease

Chronic inflammation and lymph node enlargement can lead to upper abdominal discomfort or dyspepsia-like sensations, especially in multicentric forms.

Red Flags for Rare Diseases

Chronic dyspepsia alone is not enough to diagnose a rare disease. But, if the patient also manifests systemic symptoms, such as fatigue, prolonged fever, neuropathic pain, or skin lesions; hepatosplenomegaly, recurrent or periodic abdominal attacks (episodic course), and unexplained weight loss, it’s important to investigate possible causes, especially if there are cases of genetic or metabolic diseases within the family. 

Each year, chronic or recurrent dyspeptic symptoms are reported by 10–30% of the population. Most of these cases, however, are classified as functional dyspepsia.

While it can significantly reduce quality of life, it does not shorten life expectancy and is not a precursor to serious organic diseases such as stomach cancer or peptic ulcer. Nevertheless, timely evaluation and appropriate treatment remain essential to prevent unnecessary suffering and to rule out underlying rare conditions.

References

• Ramaswami, U., & Hughes, D. A. (2016). Understanding the gastrointestinal manifestations of Fabry disease. Orphanet Journal of Rare Diseases.
• Lee, J. K., & Butterfield, J. H. (2008). Gastrointestinal manifestations of systemic mastocytosis. World Journal of Gastroenterology