Prevalence, clinical investigation, and management of gallbladder disease in Rett syndrome

Abstract

AIM This study determined the prevalence of cholelithiasis and/or cholecystectomy in Rett syndrome, described gallbladder function in a clinical cohort, and identified recommendations for assessment and management of gallbladder disease.METHOD The incidence of cholelithiasis/cholecystectomy was estimated from data describing 270 and 681 individuals with a pathogenic MECP2 mutation in the Australian Rett Syndrome Database and the International Rett Syndrome Phenotype Database respectively. Gallbladder function in 25 females (mean age 16y 5mo, SD 20y 7mo, range 3y 5mo-47y 10mo) with Rett syndrome (RTT) was evaluated with clinical assessment and ultrasound of the gallbladder. The Delphi technique was used to develop assessment and treatment recommendations. RESULTSThe incidence rate for cholelithiasis and/or cholecystectomy was 2.3 (95% confidence interval [CI] 1.1-4.2) and 1.8 (95% CI 1.0-3.0) per 1000 person-years in the Australian and International Databases respectively. The mean contractility index of the gallbladder for the clinical sample was 46.5% (SD 38.3%), smaller than for healthy individuals but similar to children with Down syndrome, despite no clinical symptoms. After excluding gastroesophageal reflux, gallbladder disease should be considered as a cause of abdominal pain in RTT and cholecystectomy recommended if symptomatic.INTERPRETATION Gallbladder disease is relatively common in RTT and should be considered in the differential diagnosis of abdominal pain in RTT.Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in the X-linked methylCpG-binding-protein-2 (MECP2) gene.1 After a period of apparently normal early development, there is a period of regression including loss of purposeful hand use and/or language skills, and the development of distinctive hand stereotypies and impaired gait. There are also supportive criteria including poor growth, respiratory irregularities, and the development of scoliosis.2 Many factors contribute to poor growth in RTT including altered oropharyngeal dysfunction and reduced food intake, 3,4 and problems with gastroesophageal motility such as reflux and constipation. 5Dysmotility may result from absent primary or secondary intestinal waves and the presence of tertiary intestinal waves as observed during videofluoroscopy, with concurrent delayed gastric emptying and atony.3 In a recent questionnaire-based survey in the USA (n=983), feeding problems were reported in 81% and gastrointestinal problems in 92% of individuals with Rett syndrome. 6 Gastrointestinal dysfunction in RTT contributes to clinical severity and affects the daily lives of the females and their caregivers. 6In general, gallstones are rare in childhood and adolescence, with estimated prevalence between 0% and 2% in the small number of studies undertaken. [7][8][9][10][11][12] However, there appears to be a higher prevalence in particular populations of children, such as those with Down syndrome, with reported prevalences up to 25%. 13,14 Clinical studies in Down syndrome indi...

Consensus guidelines on managing Rett syndrome across the lifespan

“… 69 70 Biliary tract disease is seen in young adulthood at rates similar to the general population, but due to communication impairment in RTT the presenting symptoms may be limited to irritability, weight loss and vomiting. 71 72 Studies of longevity in RTT demonstrate survival of many into middle age, underscoring the need for the early development of a comprehensive, thoughtful plan for transitioning to adulthood. 73 Longitudinal supervision is required in RTT as physical, behavioural and cognitive limitations will not allow for independent living.…”

Rett syndrome: a neurological disorder with metabolic components

“…Metabolic complications are also common in RTT. A number of patients present with dyslipidaemia [ 15 , 16 ], elevated plasma leptin and adiponectin [ 17 , 18 ], elevated ammonia [ 1 ] and inflammation of the gallbladder, an organ which stores bile for fat digestion [ 19 ]. Changes in brain carbohydrate metabolism [ 20 ] and neurometabolites associated with cell integrity and membrane turnover [ 21 , 22 ] have also been reported.…”

Phenotypes in adult patients with Rett syndrome: results of a 13-year experience and insights into healthcare transition

“…This finding has been recently proven to be relatively frequent in RTT, and should be suspected as one of the causes of abdominal pain. 28 An international consensus developed guidelines on assessment and management of GI disorders in RTT, 29 with specific focus on GERD, constipation and abdominal bloating. For these issues, conservative strategies together with pharmacological/ surgical interventions are recommended.…”