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High plasma neurotensin levels in children with Prader-Willi syndrome
Merlin G Butler1, Tommy A Nelson1, Daniel J Driscoll2
1Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, Kansas.
Insights
Prader-Willi syndrome (PWS) is a genetic obesity disorder. This study found higher neurotensin (NT) plasma levels in children with PWS compared to controls, suggesting NT’s role in PWS pathogenesis.
Area of Science:
- Endocrinology
- Genetics
- Pediatrics
Background:
- Prader-Willi syndrome (PWS) is a complex genetic disorder associated with obesity.
- Neuro-endocrine peptides are implicated in gastric function and pain perception.
- Neurotensin (NT) is a peptide that may play a role in PWS pathophysiology.
Purpose of the Study:
- To investigate plasma neurotensin (NT) levels in children with Prader-Willi syndrome (PWS).
- To compare NT levels between PWS patients and unaffected siblings.
- To explore potential correlations between NT levels and PWS subtypes.
Main Methods:
- Plasma NT levels were measured in 23 children with PWS and 18 unrelated control siblings using multiplex sandwich immunoassays.
- Data were analyzed using ANOVA, adjusting for age, gender, and BMI.
- PWS subtypes (maternal disomy 15 vs. deletion) were considered.
Main Results:
- Children with PWS exhibited significantly higher plasma NT levels (626 pg/ml) compared to controls (371 pg/ml).
- No significant correlations were found between NT levels and age, gender, or BMI.
- Higher NT levels were observed in the maternal disomy 15 subtype of PWS compared to the deletion subtype.
Conclusions:
- Elevated plasma NT levels are associated with Prader-Willi syndrome.
- Neurotensin may be a contributing factor in the development or manifestation of PWS.
- Further research is warranted to elucidate the precise role of NT in PWS symptoms like altered gastric motility and pain sensation.
Abstract:
Prader-Willi syndrome (PWS) is an obesity-related genetic condition, most commonly due to a paternal deletion of the chromosome 15q11-q13 region. PWS is characterized by growth hormone deficiency, infantile hypotonia and feeding problems, hypogenitalism/hypogonadism, increased pain threshold and thermal instability, decreased gastric motility, and hyperphagia in childhood leading to severe obesity. Neuro-endocrine peptides are known to influence gastric function and pain sensation which led us to measure a specific peptide that may be involved [i.e., neurotensin (NT)] in PWS and compared with unrelated control siblings. Overnight fasting plasma NT levels were obtained from 23 children with confirmed PWS (age: 8.2 ± 2.0 years; range: 5-11 years) and 18 unaffected, unrelated siblings (age: 8.2 ± 2.3 years; range: 5-11 years) and measured using Multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Plasma NT levels were natural log-transformed and analyzed by ANOVA with adjustments for age, gender, and body mass index (BMI). No difference was found in plasma NT levels for gender, age or BMI or significant correlations seen with age or BMI. Higher plasma NT levels (P < 0.001) were seen in PWS children (mean of 626 ± 238 pg/ml) compared with unaffected, unrelated siblings (mean of 371 ± 236 pg/ml). Plasma levels were also higher in children with maternal disomy 15 (736 ± 182 pg/ml) compared with those having the deletion subtype (548 ± 247 pg/ml, P < 0.04). Although no measures for pain threshold, thermal instability or gastric motility were performed in our study participants, higher plasma NT levels were found in PWS children.
