Chronic Intestinal Pseudoobstruction

MONDO:0017574 Pathograph 9 Show in embeddings browser

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`.

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3
Pathophys.
6
Phenotypes
9
Pathograph
2
Genes
5
Medical Actions
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.
Show evidence (1 reference)
PMID:28261062 SUPPORT Human Clinical
"a progressive metabolic disorder caused by thymidine phosphorylase (TP) enzyme deficiency"
Defines MNGIE, the mitochondrial CIPO subtype, as caused by thymidine phosphorylase deficiency with fatal gastrointestinal complications.
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 CL:0007011
enteric nervous system development GO:0048484 ⚠ ABNORMAL
intestine UBERON:0000160
Downstream
Intestinal Dysmotility
Show evidence (1 reference)
PMID:17357080 SUPPORT Human Clinical
"the filamin N terminal region between the initial two methionines is crucial for proper enteric neuron development"
Links the FLNA loss-of-function lesion to defective enteric neuron development, the proposed basis for the neuropathic CIPO node.
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 CL:0002504
smooth muscle contraction GO:0006939 ↓ DECREASED
intestine UBERON:0000160
Downstream
Intestinal Dysmotility
Show evidence (1 reference)
PMID:24777424 SUPPORT Human Clinical
"exome sequencing revealed an Arg148Ser mutation in the enteric smooth muscle actin gamma 2 (ACTG2) gene"
Demonstrates that a smooth-muscle actin (ACTG2) mutation underlies familial visceral myopathy presenting as CIPO, supporting the myopathic contractile-failure mechanism.
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 UBERON:0000160
Downstream
Intestinal Pseudo-obstruction Insufficient propulsive motility produces episodes that mimic mechanical bowel obstruction in the absence of an occluding lesion.
Abdominal Distention Luminal stasis with accumulation of gas and fluid behind dysmotile segments distends the abdomen.
Constipation Impaired colonic propulsion slows or prevents passage of stool.
Vomiting Proximal gastrointestinal stasis and retained content promote emesis.
Feeding Difficulties Impaired transit and intolerance to enteral intake produce feeding difficulties.
Failure to Thrive Chronic feeding intolerance and inadequate enteral nutrition lead to failure to thrive.
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
Show evidence (1 reference)
PMID:27683196 SUPPORT Human Clinical
"Chronic intestinal pseudo-obstruction (CIPO) represents the most severe form of gastrointestinal dysmotility with debilitating and potentially lethal consequences"
Confirms intestinal pseudo-obstruction as the defining and most severe gastrointestinal-dysmotility feature of CIPO.
Abdominal Distention Abdominal distention HP:0003270
Show evidence (1 reference)
PMID:33880338 SUPPORT Human Clinical
"The patient suffered from recurrent episodes of abdominal bloating"
Case report documents recurrent abdominal distension (bloating) as a presenting feature of CIPO.
Vomiting Vomiting HP:0002013
Constipation Constipation HP:0002019
Feeding Difficulties Feeding difficulties HP:0011968
Show evidence (1 reference)
PMID:33880338 SUPPORT Human Clinical
"had feeding difficulties, and required long-term parenteral nutrition support"
Case report documents feeding intolerance requiring long-term parenteral nutrition, the characteristic enteral-feed intolerance of CIPO.
Growth 1
Failure to Thrive Failure to thrive HP:0001508
🧬

Genetic Associations

2
FLNA (X-linked Loss-of-Function)
Gene: FLNA hgnc:3754
Show evidence (3 references)
PMID:17357080 SUPPORT Human Clinical
"bears a 2-bp deletion in exon 2 of the FLNA gene"
Identifies a loss-of-function FLNA frameshift variant as the cause of X-linked chronic idiopathic intestinal pseudo-obstruction.
PMID:17357080 SUPPORT Human Clinical
"the filamin N terminal region between the initial two methionines is crucial for proper enteric neuron development"
Mechanistically links the FLNA mutation to defective enteric neuron development, supporting the neuropathic basis of this subtype.
PMID:20871226 SUPPORT Human Clinical
"X-linked intestinal pseudo-obstruction, a rare disorder caused by mutations in FLNA, the gene encoding the cytoskeletal protein filamin A"
Confirms FLNA mutations as the cause of X-linked intestinal pseudo-obstruction, with histopathology (abnormal smooth-muscle layering) refining the neuropathic-versus-myopathic basis.
TYMP (Autosomal Recessive Loss-of-Function)
Gene: TYMP hgnc:3148
Show evidence (1 reference)
PMID:15571233 SUPPORT Human Clinical
"an autosomal recessive disorder caused by mutations in the gene encoding thymidine phosphorylase"
Establishes biallelic TYMP (thymidine phosphorylase) mutations as the autosomal recessive cause of MNGIE, the mitochondrial CIPO subtype.
💊

Medical Actions

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.
Show evidence (1 reference)
PMID:15880314 SUPPORT Human Clinical
"almost one third required long-term home parenteral nutrition"
Single-center natural-history study shows roughly one-third of adult CIPO patients depend on long-term home parenteral nutrition, the mainstay of supportive care.
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 Management NCIT:C16080
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.
Show evidence (1 reference)
PMID:27683196 SUPPORT Human Clinical
"Current treatment options invariably involve surgery and specialized nutritional support"
Review confirms surgery (e.g., decompression, venting enterostomy, resection) as a core component of CIPO management for complications of pseudo-obstruction.
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.
Show evidence (1 reference)
PMID:15880314 SUPPORT Human Clinical
"4 underwent small bowel transplantation"
Natural-history cohort documents small bowel transplantation as a salvage option in adult CIPO with irreversible intestinal failure.
Genetic Counseling
Action: Genetic Counseling NCIT:C15240
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.
  evidence:
  - reference: PMID:28261062
    reference_title: "Mitochondrial Neurogastrointestinal Encephalomyopathy Caused by Thymidine Phosphorylase Enzyme Deficiency: From Pathogenesis to Emerging Therapeutic Options."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a progressive metabolic disorder caused by thymidine phosphorylase (TP) enzyme deficiency"
    explanation: Defines MNGIE, the mitochondrial CIPO subtype, as caused by thymidine phosphorylase deficiency with fatal gastrointestinal complications.
- 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
  evidence:
  - reference: PMID:17357080
    reference_title: Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the filamin N terminal region between the initial two methionines is crucial for proper enteric neuron development"
    explanation: Links the FLNA loss-of-function lesion to defective enteric neuron development, the proposed basis for the neuropathic CIPO node.
  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
  evidence:
  - reference: PMID:24777424
    reference_title: Familial visceral myopathy diagnosed by exome sequencing of a patient with chronic intestinal pseudo-obstruction.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "exome sequencing revealed an Arg148Ser mutation in the enteric smooth muscle actin gamma 2 (ACTG2) gene"
    explanation: Demonstrates that a smooth-muscle actin (ACTG2) mutation underlies familial visceral myopathy presenting as CIPO, supporting the myopathic contractile-failure mechanism.
  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.
  downstream:
  - target: Intestinal Pseudo-obstruction
    description: >-
      Insufficient propulsive motility produces episodes that mimic mechanical
      bowel obstruction in the absence of an occluding lesion.
    causal_link_type: DIRECT
  - target: Abdominal Distention
    description: >-
      Luminal stasis with accumulation of gas and fluid behind dysmotile
      segments distends the abdomen.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Luminal gas and fluid accumulation from stasis
  - target: Constipation
    description: >-
      Impaired colonic propulsion slows or prevents passage of stool.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Impaired colonic propulsion
  - target: Vomiting
    description: >-
      Proximal gastrointestinal stasis and retained content promote emesis.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Proximal stasis with retrograde transit of retained content
  - target: Feeding Difficulties
    description: >-
      Impaired transit and intolerance to enteral intake produce feeding
      difficulties.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Enteral feed intolerance from impaired transit
  - target: Failure to Thrive
    description: >-
      Chronic feeding intolerance and inadequate enteral nutrition lead to
      failure to thrive.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Chronic feeding intolerance and malnutrition
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
  evidence:
  - reference: PMID:27683196
    reference_title: "Chronic intestinal pseudo-obstruction in children and adults: diagnosis and therapeutic options."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Chronic intestinal pseudo-obstruction (CIPO) represents the most severe form of gastrointestinal dysmotility with debilitating and potentially lethal consequences"
    explanation: Confirms intestinal pseudo-obstruction as the defining and most severe gastrointestinal-dysmotility feature of CIPO.
- 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
  evidence:
  - reference: PMID:33880338
    reference_title: Visceral myopathy diagnosed by a de novo ACTG2 mutation in a patient with chronic intestinal pseudo-obstruction-a case report.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient suffered from recurrent episodes of abdominal bloating"
    explanation: Case report documents recurrent abdominal distension (bloating) as a presenting feature of CIPO.
- 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
  evidence:
  - reference: PMID:33880338
    reference_title: Visceral myopathy diagnosed by a de novo ACTG2 mutation in a patient with chronic intestinal pseudo-obstruction-a case report.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "had feeding difficulties, and required long-term parenteral nutrition support"
    explanation: Case report documents feeding intolerance requiring long-term parenteral nutrition, the characteristic enteral-feed intolerance of CIPO.
- 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`.
  evidence:
  - reference: PMID:17357080
    reference_title: Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "bears a 2-bp deletion in exon 2 of the FLNA gene"
    explanation: Identifies a loss-of-function FLNA frameshift variant as the cause of X-linked chronic idiopathic intestinal pseudo-obstruction.
  - reference: PMID:17357080
    reference_title: Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the filamin N terminal region between the initial two methionines is crucial for proper enteric neuron development"
    explanation: Mechanistically links the FLNA mutation to defective enteric neuron development, supporting the neuropathic basis of this subtype.
  - reference: PMID:20871226
    reference_title: Diffuse abnormal layering of small intestinal smooth muscle is present in patients with FLNA mutations and x-linked intestinal pseudo-obstruction.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "X-linked intestinal pseudo-obstruction, a rare disorder caused by mutations in FLNA, the gene encoding the cytoskeletal protein filamin A"
    explanation: Confirms FLNA mutations as the cause of X-linked intestinal pseudo-obstruction, with histopathology (abnormal smooth-muscle layering) refining the neuropathic-versus-myopathic basis.
- 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.
  evidence:
  - reference: PMID:15571233
    reference_title: "Thymidine phosphorylase deficiency causes MNGIE: an autosomal recessive mitochondrial disorder."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "an autosomal recessive disorder caused by mutations in the gene encoding thymidine phosphorylase"
    explanation: Establishes biallelic TYMP (thymidine phosphorylase) mutations as the autosomal recessive cause of MNGIE, 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
  evidence:
  - reference: PMID:15880314
    reference_title: "Natural history of chronic idiopathic intestinal pseudo-obstruction in adults: a single center study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "almost one third required long-term home parenteral nutrition"
    explanation: Single-center natural-history study shows roughly one-third of adult CIPO patients depend on long-term home parenteral nutrition, the mainstay of supportive care.
- 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 Management
    term:
      id: NCIT:C16080
      label: Surgical Management
  evidence:
  - reference: PMID:27683196
    reference_title: "Chronic intestinal pseudo-obstruction in children and adults: diagnosis and therapeutic options."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Current treatment options invariably involve surgery and specialized nutritional support"
    explanation: Review confirms surgery (e.g., decompression, venting enterostomy, resection) as a core component of CIPO management for complications of pseudo-obstruction.
- 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
  evidence:
  - reference: PMID:15880314
    reference_title: "Natural history of chronic idiopathic intestinal pseudo-obstruction in adults: a single center study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "4 underwent small bowel transplantation"
    explanation: Natural-history cohort documents small bowel transplantation as a salvage option in adult CIPO with irreversible intestinal failure.
- 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: NCIT:C15240
      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.