Intestinal pseudo-obstruction

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Intestinal pseudo-obstruction is a condition characterized by impairment of the muscle contractions that move food through the digestive tract. It can occur at any time of life, and its symptoms range from mild to severe. The condition may arise from abnormalities of the gastrointestinal muscles themselves (myogenic) or from problems with the nerves that control the muscle contractions (neurogenic).

Intestinal pseudo-obstruction leads to a buildup of partially digested food in the intestines. This buildup can cause abdominal swelling (distention) and pain, nausea, vomiting, and constipation or diarrhea. Affected individuals experience loss of appetite and impaired ability to absorb nutrients, which may lead to malnutrition. These symptoms resemble those of an intestinal blockage (obstruction), but in intestinal pseudo-obstruction no blockage is found.

Depending on the cause of intestinal pseudo-obstruction, affected individuals can have additional signs and symptoms. Some people with intestinal pseudo-obstruction have bladder dysfunction such as an inability to pass urine. Other, additional features may include decreased muscle tone (hypotonia) or stiffness (spasticity) of the torso and limbs, weakness in the muscles that control eye movement (ophthalmoplegia), intellectual disability, seizures, unusual facial features, or recurrent infections.

When intestinal pseudo-obstruction occurs without additional features, it is called primary or idiopathic intestinal pseudo-obstruction. When the disorder occurs along with other signs and symptoms or as a complication of another health condition, it is called secondary intestinal pseudo-obstruction. The condition can occur once in a while (acute) or steadily (chronic).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Intestinal pseudo-obstruction can have different causes. Variants (also called mutations) in several genes can cause this condition. In some individuals with primary intestinal pseudo-obstruction, the condition is caused by genetic changes affecting the FLNA or ACTG2 gene.

The protein produced from the FLNA gene, filamin A, attaches (binds) to proteins called actins and helps them form the branching network of filaments that make up the cytoskeleton, which gives structure to cells and allows them to change shape and move. FLNA gene variants that cause intestinal pseudo-obstruction are thought to reduce levels of the filamin A protein or impair its function. Research suggests that decreased filamin A function may affect the shape of cells in the smooth muscles of the gastrointestinal tract during development before birth, causing abnormalities in the layering of these muscles. Smooth muscles line the internal organs; they contract and relax without being consciously controlled. In the gastrointestinal tract, abnormal layering of these muscles interferes with the ability to produce the coordinated waves of contractions (peristalsis) that move food along during digestion.

A loss (deletion) or copy (duplication) of genetic material can affect all or part of the FLNA gene, and may also include adjacent genes on the X chromosome. Changes in adjacent genes may account for some of the other signs and symptoms that can occur with intestinal pseudo-obstruction.

The ACTG2 gene provides instructions for making a member of the actin family called gamma (γ)-2 actin. The γ-2 actin protein is found in smooth muscle cells of the intestinal and urinary tracts. It is necessary for contraction of the smooth muscles in the intestines and bladder. These contractions move food through the intestines as part of the digestive process and empty urine from the bladder. ACTG2 gene variants hinder the formation of actin filaments in the cytoskeleton and reduce the ability of smooth muscles in the intestines and bladder to contract, leading to the signs and symptoms of intestinal pseudo-obstruction.

Variants in other genes involved in smooth muscle contraction can also cause intestinal pseudo-obstruction. Studies suggest additional gene variants that have not been identified can also result in this condition.

Secondary intestinal pseudo-obstruction occurs as a complication of other disorders that damage muscles or nerves in the intestinal tract, such as Parkinson's disease, type 2 diabetes, various types of muscular dystrophy, or Kawasaki disease. Additionally, intestinal pseudo-obstruction can occur with certain inherited syndromes such as megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) or mitochondrial neurogastrointestinal encephalopathy disease (MNGIE disease).

Environmental factors, such as infections, surgery, or certain drugs can also cause secondary intestinal pseudo-obstruction. In some affected individuals, the cause of intestinal pseudo-obstruction is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

When intestinal pseudo-obstruction is caused by genetic factors, it can have different inheritance patterns. However, intestinal pseudo-obstruction is usually not inherited, and most affected individuals do not have a family history of the disorder.

When, intestinal pseudo-obstruction is caused by FLNA gene variants is inherited in an X-linked pattern. The FLNA gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome) a variant in the only copy of the gene in each cell is sufficient to cause the condition. In females (who have two copies of the X chromosome) one altered copy of the gene may or may not cause features of the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

When intestinal pseudo-obstruction is caused by ACTG2 gene variants, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Some other cases of intestinal pseudo-obstruction are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The overall prevalence of intestinal pseudo-obstruction is unknown. Researchers in Japan have estimated the prevalence of chronic intestinal pseudo-obstruction in that country as 9 cases per million people.

Which doctor should you see?

The suggested department for discussing Intestinal pseudo-obstruction is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Intestinal pseudo-obstruction. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.