Alternating Hemiplegia of Childhood: gastrointestinal manifestations and correlation with neurological impairments

Orphanet J Rare Dis. 2020 Sep 3;15(1):231. doi: 10.1186/s13023-020-01474-w.


Background: Alternating Hemiplegia of Childhood (AHC) is caused by mutations of the ATP1A3 gene which is expressed in brain areas that include structures controling autonomic, gastrointestinal, gut motility and GABAergic functions. We aimed to investigate, in a cohort of 44 consecutive AHC patients, two hypotheses: 1) AHC patients frequently manifest gastrointestinal, particularly motility, problems. 2) These problems are often severe and their severity correlates with neurological impairments.

Results: 41/44 (93%) exhibited gastrointestinal symptoms requiring medical attention. For these 41 patients, symptoms included constipation (66%), swallowing problems (63%), vomiting (63%), anorexia (46%), diarrhea (44%), nausea (37%), and abdominal pain (22%). Symptoms indicative of dysmotility occurred in 33 (80%). The most common diagnoses were oropharyngeal dysphagia (63%) and gastroesophageal reflux (63%). 16 (39%) required gastrostomy and two fundoplication. Severity of gastrointestinal symptoms correlated with non-paroxysmal neurological disability index, Gross Motor Function Classification System scores, and with the presence/absence of non-gastrointestinal autonomic dysfunction (p = 0.031, 0.043, Spearman correlations and 0.0166 Cramer's V, respectively) but not with the paroxysmal disability index (p = 0.408).

Conclusions: Most AHC patients have gastrointestinal problems. These are usually severe, most commonly are indicative of dysmotility, often require surgical therapies, and their severity correlates with that of non-paroxysmal CNS manifestations. Our findings should help in management-anticipatory guidance of AHC patients. Furthermore, they are consistent with current understandings of the pathophysiology of AHC and of gastrointestinal dysmotility, both of which involve autonomic and GABAergic dysfunction.

Keywords: ATP1A3; Alternating hemiplegia of childhood; GMFCS; Non-paroxysmal disability index.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hemiplegia*
  • Humans
  • Mutation
  • Sodium-Potassium-Exchanging ATPase* / genetics


  • ATP1A3 protein, human
  • Sodium-Potassium-Exchanging ATPase

Supplementary concepts

  • Alternating hemiplegia of childhood