Study Links Worse Angelman GI Symptoms to Problems in Infancy

Early reflux, night sweats may ID AS children at risk of GI problems

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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A history of reflux and night sweats during infancy may help identify children and adolescents with Angelman syndrome who are at higher risk for more gastrointestinal (GI) symptoms, according to a new study.

“GI symptoms were found to be very common in people with AS and significant associations were identified between high frequency GI symptoms and infancy history,” the researchers wrote.

The scientists say their findings seek to shed new light on “the relationship between the history of people with AS in their infancy and GI symptoms as they age.”

The study, “Association between early and current gastro-intestinal symptoms and co-morbidities in children and adolescents with Angelman syndrome,” was published in the Journal of Intellectual Disability Research.

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AS is a complex disorder caused by genetic defects in the UBE3A gene that codes for an enzyme active in the brain.

People inherit two copies of this gene — one from each biological parent — but only the maternally-inherited copy is typically active. That copy of UBE3A is “turned on” in specific regions of the brain, while the copy inherited from the father gets “turned off” through a process called imprinting.

In addition to severe intellectual disability, AS patients often have other simultaneous health complications, called comorbidities. These can include GI symptoms, epilepsy, sleep problems, toileting issues, and behavioral problems.

Investigating GI symptoms in AS

GI complications, which can affect up to 87% of AS patients, are among the criteria employed in the diagnosis of the disease. Clinicians assess the occurrence of constipation, diarrhea, repeated vomiting, and gastroesophageal reflux, known as acid reflux.

These symptoms can worsen sleep and behavioral problems, leading to a poorer social development. Yet, the causes behind them are not well understood.

Now, researchers in Ireland and Australia sought to identify potential links between GI complications and other conditions/symptoms in AS — as well as early predictors of gastrointestinal symptoms. To that end, they analyzed data from 173 children and adolescents with AS.

All patients were enrolled in the Global Angelman Syndrome Registry. It assembles data from more than 1,800 AS patients across 80 countries through surveys completed by parents or caregivers about diagnosis, development history, behaviors, and clinical status.

The children’s ages ranged from 3 to 17 — with a mean age of 8.38 — and 50.29% were male.

A genetically confirmed AS diagnosis was reported for 93.06% of patients. Among them, the most common genetic cause of AS — in 61.49% of patients — was a deletion of a region of the maternally inherited chromosome 15 that contains UBE3A.

This was followed by a mutation in the UBE3A gene itself (21%), uniparental disomy (8.7%), and imprinting errors (4.97%). Uniparental disomy is a biological phenomenon in which a person inherits two copies of the chromosome from the father and none from the mother. Other causes accounted for 3.11% of cases.

Results showed that 147 patients (84%) experienced constipation, making this the most common GI symptom. Next was reflux (64%), followed by vomiting with feeds (58%).

Only 22 participants (12.7%) had no GI symptoms. A total of 60 patients had one such symptom (34.7%), 60 others experienced two (34.7%), and 31 (17.9%) had all three GI symptoms — constipation, reflux, and vomiting.

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Researchers then compared AS patients with two or more GI symptoms (91 participants) with those showing only one or none (82 participants) to understand which early factors might correlate with gastrointestinal symptoms.

Results showed that the presence of more GI symptoms was significantly associated with a more frequent infancy history of refusal to nurse, vomiting, arching the back, difficulty in gaining weight, reflux, and solid food transition.

Links to problems in infancy

Patients with a higher frequency of GI symptoms also were significantly more likely to have experienced other health problems, have diagnosed intolerances, and have a history of tube feeding in infancy relative to those with less frequent gastrointestinal problems.

In addition, nighttime urination and night sweats during infancy were significantly more frequent in the group with more GI symptoms, the data showed.

“Sweating can result from problems in temperature regulation, that are common in AS, and it can be a sign of discomfort, perhaps caused by gastroesophageal reflux,” the researchers wrote.

No significant links were detected between more current GI symptoms and an infancy history of language and communication complications or challenging behavior.

Notably, further analyses showed that gastroesophageal reflux, strep throat, and night sweats during infancy were significant predictors of more future GI symptoms in children and adolescents with AS. Strep throat is a bacterial infection that causes a severe sore throat.

These findings suggest that behaviors during infancy “may be associated with an increased likelihood of developing GI symptoms,” the researchers wrote, noting, however, that “further studies are needed to replicate and consolidate these findings.”

“This study has extended knowledge on AS and it has provided novel findings on GI symptom co-morbidity in children and adolescents with AS,” the team wrote.

Overall, these findings “may inform clinical professionals about the co-occurring symptoms of GI in people with AS, particularly those that might exacerbate night-time continence problems and sleep problems,” the researchers concluded.

Future studies should confirm whether these associations are also observed in the adult AS population, according to the team.