Ask OpenScientist

Ask a research question about Chronic Intestinal Pseudoobstruction. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

3
Pathophys.
6
Phenotypes
3
Pathograph
2
Genes
5
Treatments
4
Subtypes
1
Deep Research

Subtypes

4
Neuropathic CIPO (incl. FLNA-related) MONDO:0010232
Primary CIPO due to defects of the enteric nervous system — enteric-neuron developmental failure (e.g., X-linked FLNA loss-of-function, curated as `FLNA_Intestinal_Pseudoobstruction`), enteric ganglionitis, or other neuropathic mechanisms.
Myopathic CIPO (visceral myopathy)
Primary CIPO due to intestinal smooth-muscle dysfunction, including familial and sporadic visceral myopathies with poorly contractile or acontractile smooth muscle. No dedicated subtype dismech entry yet; specific visceral-myopathy gene entries are scoped as follow-up curation.
Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) MONDO:0011283
CIPO arising from mitochondrial DNA depletion / instability (classically due to TYMP deficiency) with combined gastrointestinal dysmotility, leukoencephalopathy, peripheral neuropathy, and external ophthalmoplegia. MONDO:0011283 (mitochondrial DNA depletion syndrome 1) is the canonical grounding for MNGIE.
Idiopathic
CIPO without an identified neuropathic, myopathic, mitochondrial, or secondary cause after appropriate work-up. A substantial fraction of childhood- and adult-onset CIPO remains in this category.

Pathophysiology

3
Enteric Neuron Developmental Failure
Neuropathic CIPO arises from defects of the enteric nervous system — most commonly failed enteric-neuron development or maintenance. The flagship example is X-linked FLNA loss-of-function, in which the truncated filamin A protein fails to support proper enteric neuron development; ganglionitis and other primary neuropathic mechanisms also feed this node.
enteric neuron link
enteric nervous system development link ⚠ ABNORMAL
intestine link
Smooth Muscle Contractile Failure
Myopathic CIPO arises from intrinsic smooth-muscle defects of the intestinal wall — poorly contractile or acontractile smooth muscle that cannot generate the propulsive contractions needed for peristalsis, regardless of the integrity of the enteric nervous system. Familial and sporadic visceral myopathies, as well as mitochondrial bioenergetic failure of smooth muscle in MNGIE, feed this node.
enteric smooth muscle cell link
smooth muscle contraction link ↓ DECREASED
intestine link
Intestinal Dysmotility
The shared physiological endpoint across CIPO subtypes is insufficient or absent propulsive intestinal motility, producing episodes that mimic mechanical obstruction. Upstream neuropathic (enteric-neuron developmental failure) and myopathic (smooth-muscle contractile failure) lesions converge on this endpoint.
intestine link
Show evidence (1 reference)
DOI:10.3389/fped.2022.837462 SUPPORT Human Clinical
"Chronic intestinal pseudo-obstruction is a rare disorder and represents the most severe form of gastrointestinal dysmotility with significant morbidity and mortality."
Pediatric review directly supports CIPO as the most severe gastrointestinal-dysmotility disorder with high morbidity and mortality.

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Chronic Intestinal Pseudoobstruction Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.

Phenotypes

6
Digestive 5
Intestinal Pseudo-obstruction Intestinal pseudo-obstruction (HP:0004389)
Abdominal Distention Abdominal distention (HP:0003270)
Vomiting Vomiting (HP:0002013)
Constipation Constipation (HP:0002019)
Feeding Difficulties Feeding difficulties (HP:0011968)
Growth 1
Failure to Thrive Failure to thrive (HP:0001508)
🧬

Genetic Associations

2
FLNA (X-linked Loss-of-Function)
TYMP (Autosomal Recessive Loss-of-Function)
💊

Treatments

5
Parenteral Nutrition
Action: total parenteral nutrition Ontology label: Total Parenteral Nutrition NCIT:C29484
Total parenteral nutrition is the mainstay of supportive care for patients whose intestinal motility cannot sustain adequate enteral caloric and fluid intake; long-term TPN dependence is a major determinant of morbidity.
Enteral Nutritional Support
Action: dietary intervention MAXO:0000088
Enteral feeding (oral, naso-jejunal, or gastrostomy / jejunostomy) is preferred when tolerated, both to maintain mucosal integrity and to limit the complications of long-term parenteral nutrition.
Surgical Management
Action: surgical procedure MAXO:0000004
Targeted surgical procedures (decompression, venting enterostomy, resection of dysfunctional segments) are used for complications of pseudo-obstruction such as severe distension, volvulus, or bowel-segment dysfunction.
Intestinal Transplantation
Action: organ transplantation MAXO:0010039
Intestinal (or multivisceral) transplantation is considered for patients with irreversible intestinal failure who have life- threatening complications of long-term parenteral nutrition.
Genetic Counseling
Action: genetic counseling MAXO:0000079
Genetic counseling is appropriate when a heritable subtype is identified or suspected (e.g., X-linked FLNA-associated CIPO, autosomal mitochondrial or visceral-myopathy syndromes).
{ }

Source YAML

click to show
name: Chronic Intestinal Pseudoobstruction
creation_date: '2026-05-12T00:00:00Z'
updated_date: '2026-05-12T19:00:00Z'
description: >-
  Chronic intestinal pseudoobstruction (CIPO) is a rare, severe disorder
  of gastrointestinal motility in which patients have episodes that mimic
  mechanical bowel obstruction — abdominal distension, vomiting,
  constipation, and inability to tolerate enteral feeds — in the absence
  of any physical luminal blockage. It is mechanistically heterogeneous:
  primary forms arise from defects of the enteric nervous system
  (neuropathic CIPO, including X-linked FLNA-associated CIPO),
  intestinal smooth muscle (myopathic CIPO), or mitochondrial DNA
  maintenance (mitochondrial neurogastrointestinal encephalomyopathy /
  MNGIE), and a substantial fraction remain idiopathic. Pediatric CIPO
  (PIPO) is recognised as biologically and clinically distinct from
  adult CIPO. The disease carries significant long-term morbidity from
  bowel-failure complications, parenteral-nutrition dependence, and
  recurrent surgery; in the most severe cases intestinal transplantation
  is considered. Subtype-specific molecular detail for X-linked FLNA
  CIPO is curated separately as `FLNA_Intestinal_Pseudoobstruction`.
categories:
- Gastrointestinal Motility Disorder
- Enteric Neuropathy
- Rare Disease
has_subtypes:
- name: Neuropathic
  display_name: Neuropathic CIPO (incl. FLNA-related)
  subtype_term:
    preferred_term: intestinal pseudoobstruction, neuronal, X-linked
    term:
      id: MONDO:0010232
      label: intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked
  description: >-
    Primary CIPO due to defects of the enteric nervous system —
    enteric-neuron developmental failure (e.g., X-linked FLNA
    loss-of-function, curated as `FLNA_Intestinal_Pseudoobstruction`),
    enteric ganglionitis, or other neuropathic mechanisms.
- name: Myopathic
  display_name: Myopathic CIPO (visceral myopathy)
  description: >-
    Primary CIPO due to intestinal smooth-muscle dysfunction, including
    familial and sporadic visceral myopathies with poorly contractile
    or acontractile smooth muscle. No dedicated subtype dismech entry
    yet; specific visceral-myopathy gene entries are scoped as
    follow-up curation.
- name: Mitochondrial
  display_name: Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
  subtype_term:
    preferred_term: MNGIE
    term:
      id: MONDO:0011283
      label: mitochondrial DNA depletion syndrome 1
  description: >-
    CIPO arising from mitochondrial DNA depletion / instability
    (classically due to TYMP deficiency) with combined
    gastrointestinal dysmotility, leukoencephalopathy, peripheral
    neuropathy, and external ophthalmoplegia. MONDO:0011283
    (mitochondrial DNA depletion syndrome 1) is the canonical
    grounding for MNGIE.
- name: Idiopathic
  description: >-
    CIPO without an identified neuropathic, myopathic, mitochondrial,
    or secondary cause after appropriate work-up. A substantial
    fraction of childhood- and adult-onset CIPO remains in this
    category.
pathophysiology:
- name: Enteric Neuron Developmental Failure
  description: >-
    Neuropathic CIPO arises from defects of the enteric nervous system
    — most commonly failed enteric-neuron development or maintenance.
    The flagship example is X-linked FLNA loss-of-function, in which
    the truncated filamin A protein fails to support proper enteric
    neuron development; ganglionitis and other primary neuropathic
    mechanisms also feed this node.
  cell_types:
  - preferred_term: enteric neuron
    term:
      id: CL:0007011
      label: enteric neuron
  biological_processes:
  - preferred_term: enteric nervous system development
    modifier: ABNORMAL
    term:
      id: GO:0048484
      label: enteric nervous system development
  locations:
  - preferred_term: intestine
    term:
      id: UBERON:0000160
      label: intestine
  downstream:
  - target: Intestinal Dysmotility
    causal_link_type: DIRECT
- name: Smooth Muscle Contractile Failure
  description: >-
    Myopathic CIPO arises from intrinsic smooth-muscle defects of the
    intestinal wall — poorly contractile or acontractile smooth muscle
    that cannot generate the propulsive contractions needed for
    peristalsis, regardless of the integrity of the enteric nervous
    system. Familial and sporadic visceral myopathies, as well as
    mitochondrial bioenergetic failure of smooth muscle in MNGIE,
    feed this node.
  cell_types:
  - preferred_term: enteric smooth muscle cell
    term:
      id: CL:0002504
      label: enteric smooth muscle cell
  biological_processes:
  - preferred_term: smooth muscle contraction
    modifier: DECREASED
    term:
      id: GO:0006939
      label: smooth muscle contraction
  locations:
  - preferred_term: intestine
    term:
      id: UBERON:0000160
      label: intestine
  downstream:
  - target: Intestinal Dysmotility
    causal_link_type: DIRECT
- name: Intestinal Dysmotility
  description: >-
    The shared physiological endpoint across CIPO subtypes is
    insufficient or absent propulsive intestinal motility, producing
    episodes that mimic mechanical obstruction. Upstream neuropathic
    (enteric-neuron developmental failure) and myopathic (smooth-muscle
    contractile failure) lesions converge on this endpoint.
  locations:
  - preferred_term: intestine
    term:
      id: UBERON:0000160
      label: intestine
  evidence:
  - reference: DOI:10.3389/fped.2022.837462
    reference_title: "Pediatric Intestinal Pseudo-Obstruction: Progress and Challenges"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Chronic intestinal pseudo-obstruction is a rare disorder and represents the most severe form of gastrointestinal dysmotility with significant morbidity and mortality."
    explanation: Pediatric review directly supports CIPO as the most severe gastrointestinal-dysmotility disorder with high morbidity and mortality.
phenotypes:
- category: Gastrointestinal
  name: Intestinal Pseudo-obstruction
  description: >-
    Recurrent episodes that mimic mechanical bowel obstruction in the
    absence of physical luminal blockage. The defining clinical feature
    of the disease across all etiological subtypes.
  phenotype_term:
    preferred_term: Intestinal pseudo-obstruction
    term:
      id: HP:0004389
      label: Intestinal pseudo-obstruction
- category: Gastrointestinal
  name: Abdominal Distention
  description: >-
    Abdominal distension from failed propulsive motility; often the most
    visible sign of obstructive episodes.
  phenotype_term:
    preferred_term: Abdominal distention
    term:
      id: HP:0003270
      label: Abdominal distention
- category: Gastrointestinal
  name: Vomiting
  description: >-
    Recurrent vomiting reflecting failed gastrointestinal transit during
    pseudo-obstructive episodes.
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
- category: Gastrointestinal
  name: Constipation
  description: >-
    Severe constipation from impaired intestinal propulsion; may
    alternate with episodes of pseudo-obstruction.
  phenotype_term:
    preferred_term: Constipation
    term:
      id: HP:0002019
      label: Constipation
- category: Gastrointestinal
  name: Feeding Difficulties
  description: >-
    Inability to tolerate enteral nutrition during active disease,
    often necessitating parenteral nutritional support.
  phenotype_term:
    preferred_term: Feeding difficulties
    term:
      id: HP:0011968
      label: Feeding difficulties
- category: Gastrointestinal
  name: Failure to Thrive
  description: >-
    Growth failure in pediatric CIPO from chronic malnutrition and
    inability to maintain adequate enteral intake.
  phenotype_term:
    preferred_term: Failure to thrive
    term:
      id: HP:0001508
      label: Failure to thrive
genetic:
- name: FLNA
  gene_term:
    preferred_term: FLNA
    term:
      id: hgnc:3754
      label: FLNA
  association: X-linked Loss-of-Function
  notes: >-
    Loss-of-function variants in FLNA (including frameshift variants
    and Xq28 duplications) cause X-linked CIPO with periventricular
    nodular heterotopia and bladder involvement. Subtype-specific
    detail is curated in `FLNA_Intestinal_Pseudoobstruction`.
- name: TYMP
  gene_term:
    preferred_term: TYMP
    term:
      id: hgnc:3148
      label: TYMP
  association: Autosomal Recessive Loss-of-Function
  notes: >-
    Biallelic TYMP (thymidine phosphorylase) loss-of-function variants
    cause MNGIE through mitochondrial DNA depletion and instability,
    with CIPO as the cardinal gastrointestinal feature. A dedicated
    dismech MNGIE entry is scoped as follow-up curation; here TYMP is
    listed as the canonical genetic cause of the mitochondrial CIPO
    subtype.
treatments:
- name: Parenteral Nutrition
  description: >-
    Total parenteral nutrition is the mainstay of supportive care for
    patients whose intestinal motility cannot sustain adequate enteral
    caloric and fluid intake; long-term TPN dependence is a major
    determinant of morbidity.
  treatment_term:
    preferred_term: total parenteral nutrition
    term:
      id: NCIT:C29484
      label: Total Parenteral Nutrition
- name: Enteral Nutritional Support
  description: >-
    Enteral feeding (oral, naso-jejunal, or gastrostomy / jejunostomy)
    is preferred when tolerated, both to maintain mucosal integrity
    and to limit the complications of long-term parenteral nutrition.
  treatment_term:
    preferred_term: dietary intervention
    term:
      id: MAXO:0000088
      label: dietary intervention
- name: Surgical Management
  description: >-
    Targeted surgical procedures (decompression, venting enterostomy,
    resection of dysfunctional segments) are used for complications of
    pseudo-obstruction such as severe distension, volvulus, or
    bowel-segment dysfunction.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
- name: Intestinal Transplantation
  description: >-
    Intestinal (or multivisceral) transplantation is considered for
    patients with irreversible intestinal failure who have life-
    threatening complications of long-term parenteral nutrition.
  treatment_term:
    preferred_term: organ transplantation
    term:
      id: MAXO:0010039
      label: organ transplantation
- name: Genetic Counseling
  description: >-
    Genetic counseling is appropriate when a heritable subtype is
    identified or suspected (e.g., X-linked FLNA-associated CIPO,
    autosomal mitochondrial or visceral-myopathy syndromes).
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
notes: >-
  This entry is a root-level dismech record for chronic intestinal
  pseudoobstruction, organising the major mechanistic categories
  (neuropathic, myopathic, mitochondrial / MNGIE, idiopathic).
  Subtype-specific molecular detail for the X-linked FLNA neuropathic
  form is curated in `FLNA_Intestinal_Pseudoobstruction`. Dedicated
  entries for visceral myopathies and for MNGIE are scoped as
  follow-up curation. Phenotype `frequency:` tags were intentionally
  omitted from this root entry because the cited literature in scope
  here supports the existence of these features in CIPO but does not
  provide subtype-pooled quantitative frequencies; reintroduce them
  per the frequency-evidence SOP once dedicated cohort data are
  curated.
disease_term:
  preferred_term: chronic intestinal pseudoobstruction
  term:
    id: MONDO:0017574
    label: chronic intestinal pseudoobstruction
📚

References & Deep Research

Deep Research

1
Chronic Intestinal Pseudoobstruction Deep Research Fallback

Chronic Intestinal Pseudoobstruction Deep Research Fallback

Provider Attempts

No deep-research provider was invoked for this root-level entry. The existing subtype dismech entry (FLNA_Intestinal_Pseudoobstruction) has its own -deep-research-falcon.md artifact from prior curation; this root-level record was curated directly from the verified literature already cached in references_cache/ for the FLNA-CIPO subtype, plus the foundational DOI:10.3389/fped.2022.837462 pediatric-CIPO review, plus ORPHA-grounded subtype identifiers for the X-linked and mitochondrial forms.

Integrated Literature Synthesis

Chronic intestinal pseudoobstruction (CIPO) is a rare, severe disorder of gastrointestinal motility in which patients experience episodes that mimic mechanical bowel obstruction in the absence of any physical luminal blockage. The pediatric review DOI:10.3389/fped.2022.837462 ("Pediatric Intestinal Pseudo-Obstruction: Progress and Challenges") frames CIPO as "the most severe form of gastrointestinal dysmotility with significant morbidity and mortality." That review also distinguishes Pediatric Intestinal Pseudo-Obstruction (PIPO) as biologically and clinically distinct from adult CIPO.

Mechanistic heterogeneity. Primary CIPO partitions along three mechanistic axes that this root entry models as separate atomic pathophysiology nodes converging on a shared Intestinal Dysmotility endpoint:

  • Neuropathic (enteric nervous system defects). The flagship example is X-linked FLNA loss-of-function (PMID:17357080, PMID:18854860), curated in the existing FLNA_Intestinal_Pseudoobstruction dismech entry. The truncated filamin A protein fails to support proper enteric neuron development. Other neuropathic mechanisms include enteric ganglionitis and acquired enteric neuropathies.
  • Myopathic (visceral myopathies). Intrinsic smooth-muscle defects produce poorly contractile or acontractile intestinal smooth muscle. No dedicated dismech entry yet for the visceral-myopathy gene set (e.g., ACTG2, MYLK, MYH11, LMOD1) — scoped as follow-up curation.
  • Mitochondrial / MNGIE. Mitochondrial DNA depletion / instability, classically due to biallelic TYMP (thymidine phosphorylase) loss-of-function, causes mitochondrial neurogastrointestinal encephalomyopathy. MONDO:0011283 (mitochondrial DNA depletion syndrome 1) is the canonical MONDO grounding; this root entry lists TYMP under genetic[] so that a future dedicated MNGIE dismech entry has a starting point.

Clinical syndrome. Six core phenotypes are captured (Intestinal pseudo-obstruction HP:0004389, Abdominal distention HP:0003270, Vomiting HP:0002013, Constipation HP:0002019, Feeding difficulties HP:0011968, Failure to thrive HP:0001508). Frequency tags were deliberately omitted from this root entry per the dismech frequency-evidence SOP — the cited literature supports the existence of these features in CIPO but does not provide subtype-pooled quantitative frequencies appropriate for the umbrella entry.

Management. The supportive-care ladder is captured in treatments[]: parenteral nutrition (NCIT:C29484, the mainstay for patients whose motility cannot sustain enteral intake), enteral nutritional support (MAXO:0000088, preferred when tolerated), surgical management (MAXO:0000004), intestinal transplantation (MAXO:0010039, reserved for irreversible intestinal failure with TPN complications), and genetic counseling (MAXO:0000079) for heritable subtypes.

Out of scope for the root entry

  • Subtype-specific molecular detail for X-linked FLNA-CIPO — already curated in FLNA_Intestinal_Pseudoobstruction.
  • MNGIE / mitochondrial DNA depletion mechanisms beyond the TYMP genetic link — scoped as a dedicated dismech entry.
  • Visceral-myopathy gene-level entries (ACTG2, MYLK, MYH11, LMOD1, etc.) — scoped as follow-up.
  • Secondary CIPO (postsurgical, post-infectious, paraneoplastic, systemic-sclerosis-associated, drug-induced) — explicitly excluded from the primary-CIPO categories enumerated here.