Comprehensive Diagnosis Needed to Pinpoint Pediatric Obesity Causes, Study Suggests

Comprehensive Diagnosis Needed to Pinpoint Pediatric Obesity Causes, Study Suggests
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A broad diagnostic approach that takes into account genetics, hormonal changes, cognitive impairments, and medication use may help identify the underlying cause of pediatric obesity in almost 20% of cases, a Dutch study says.

Titled “Identifying underlying medical causes of pediatric obesity: Results of a systematic diagnostic approach in a pediatric obesity center,” the study was published in the journal PLOS One.

Across several countries, the prevalence of severe obesity in children and adolescents — as defined by the World Health Organization and the International Obesity Task Force — ranges from 1.7 to 6.3%.

Yet, the condition rarely can be attributed to a single underlying feature, such as genetic traits or hormonal imbalances. Instead, the mechanisms underlying childhood obesity are complex.

However, scientists say, establishing an early diagnosis can help tailor treatments for the best responses.

The Endocrine Society (ES) published a clinical practice guideline in 2017 for the evaluation and treatment of pediatric patients with obesity. This guide suggests specific diagnostic steps depending on the outcomes of physical examinations and detailed patient histories.

Nonetheless, “it is difficult to assess which patients should be evaluated for underlying causes,” the researchers wrote.

Now, a team from the Netherlands applied a diagnostic approach that takes into account all of the possible underlying medical causes of obesity mentioned in the ES guidelines. Specifically, it includes endocrine and genetic conditions, as well as cerebral injury and medication use.

In their study, the investigators evaluated 282 patients (median age 10.8) referred to the Obesity Clinic CGG, in Rotterdam, who underwent the complete diagnosis protocol, including genetic analysis. The referral for most of the patients was due to a suspicion of an underlying disease.

Median body mass index or BMI — a measure of body fat — standardized for age was 3.7, indicative of severe obesity. Among the patients, 183 (64.9%) were Dutch and 67 (23.8%) had some level of intellectual disability.

An underlying medical cause of obesity was identified in 54 participants (19.1%), including 37 genetic diseases, nine cases of medication-induced obesity, and eight due to cerebral injuries. For the remaining 228 patients — 80.9% of the children — no single cause of obesity was identified.

However, the researchers said that genetic variants likely were the cause of obesity in an additional 17 patients, although further testing would be required to confirm the link.

Of the 37 individuals with genetic obesity, 18 had associated intellectual disability.

Mutations in the MC4R gene were the most common cause of genetic obesity, found in nine patients (3.2%). A link between MC4R gene changes and obesity is well known. Other genetic variants were found in the LEPR (six patients) and GNAS genes (five participants).

In five of the eight cases of brain injury, a rapid onset of weight gain paralleled intracranial surgery and/or radiation therapy. Other causes were linked to congenital birth defects and meningitis.

Six of the patients with medication-induced obesity were chronically treated with inhaled corticosteroids. In these cases, intensified use of these corticosteroids was simultaneous to a sudden weight gain.

Individuals with genetic mutations had a significant early onset of obesity (under age 5) and hyperphagia, or excessive hunger, compared with patients whose disease did not have a single cause, the researchers observed. In contrast, factors including obesity in parents, and psychosocial problems, were less frequent in the group with obesity due to genetic causes.

“In conclusion, we show that a large variety of underlying medical obesity diagnoses can be established in pediatric patients with obesity in tertiary care setting when using a comprehensive diagnostic workup,” the scientists wrote.

“Investigating endocrine, genetic, cerebral and medication-induced causes of obesity is needed for these patients to facilitate disease-specific and patient-tailored treatment,” they added.

In addition, further studies to identify markers of underlying diseases for obesity “are needed to improve identification of these patients,” the team said.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
Total Posts: 9

José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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