The patient was born after a 36-week, uncomplicated pregnancy and was delivered vaginally with a
birthweight of 3.8 kg (36th
percentile). He was breastfed for the first month of life. The patient had
normal physical and language development. He began walking at age 11 months and his height had
always tracked along the 50th
The patient had been home-schooled since the age of 11 years, owing to his anxiety and difficulties
that arose from being bullied by peers. In the state where the patient's family lived, the law required
only written notice on the part of the parent of their intent to home-school a child and maintenance of
current immunization records. No requirement for routine physical examination or health screening
existed for home-schooled children, although this patient did have regular check-ups with his primary-
care physician. The patient lived at home with his parents, who were both medically disabled—the
father from complications of a meningioma and the mother from debilitating arthritis. In addition, both
parents had a history of obesity, hypertension and type 2 diabetes mellitus. His mother had
undergone gastric-bypass surgery 2 years before the patient's presentation at the adolescent obesity
The patient had in the past participated in numerous diet and exercise programs under the guidance
and direction of his primary-care physician, including meal-replacement products, over-the-counter
dietary supplements, nutritional counseling and a prescribed exercise program with a personal trainer.
Despite initial success with these interventions, any weight loss he achieved was temporary, with
return to baseline weight, plus 4.5–9.0 kg of additional weight.
Dietary recall of the previous 24 h was undertaken at the time of the patient's initial interview at the
adolescent obesity clinic. The recall test revealed that the portion sizes of the patient's meals were
excessive. He ate multiple courses at each sitting, snacked frequently, consumed approximately 450
kcals daily from sweetened beverages and ate fast food on average three times per week. Meals at
home were served 'restaurant-style', with plates prepared in the kitchen and then brought to the table,
and consumed while watching television. An assessment of the patient's physical activity, also
undertaken at the initial interview, revealed that the total time he spent in front of a screen was around
6 h per day, with an average of 4 h spent watching television, 1 h of playing video games and 1 h of
computer time per day; these times increased on weekends. He had not performed any regular
physical activity since he left regular school.
Before his referral to the adolescent obesity clinic, the patient's primary-care physician had
undertaken a genetic evaluation, in which they looked for a potential etiology for his obesity. This
included high-resolution chromosomal analysis, which showed the patient to be a normal male with a
46,XY karyotype, who had no consistent, detectable abnormalities of chromosome number or
structure. In addition, southern blot analysis demonstrated a normal methylation pattern of the
Prader–Willi loci on the long arm of chromosome 15, which indicated that the patient was unlikely to
have either Prader–Willi or Angelman syndrome. Finally, single-gene tests for defects in the
melanocortin-4 receptor (MCR4) were performed, which showed no sequence variants to indicate the
presence of an MCR4 mutation.
After the patient's initial evaluation in the adolescent obesity clinic, further tests were performed after
an overnight fast. These tests revealed a total cholesterol level of 5.13 mmol/l (standard range <5.18
mmol/l), HDL cholesterol level of 0.65 mmol/l (standard range 0.88–1.53 mmol/l), LDL cholesterol
level of 3.70 mmol/l (standard range <2.59 mmol/l) and a triglyceride level of 2.49 mmol/l (standard
range 0.36–1.51 mmol/l). Liver-function tests revealed an aspartate aminotransferase level of 0.90
µkat/l (standard range 0.25–0.66 µkat/l), alanine aminotransferase level of 1.85 µkat/l (standard range
0.50–1.09 µkat/l), γ-glutamyltransferase level of 1.23 µkat/l (standard range 0.08–0.91 µkat/l), and
total bilirubin level of 6.8 µmol/l (standard range 3.4–20.5 µmol/l). Insulin level was 1,069.5 pmol/l
(standard range 13.8–201.6 pmol/l) and serum glucose level was 5.5 mmol/l (standard range 3.3–5.8
mmol/l). Results at 2 h after administration of an oral glucose tolerance test revealed a serum glucose
level of 8.3 mmol/l (normal range <7.8 mmol/l). Hepatic ultrasonography showed no evidence of
biliary stones or dilation of the biliary tree, but rather generalized, increased echogenicity of the liver,
which is consistent with fatty infiltration.
With a BMI of 52.3 kg/m2
, the patient satisfied adult criteria for morbid obesity. Furthermore, on the
basis of his increased waist circumference, elevated blood pressure, elevated triglyceride levels, and
low HDL cholesterol level, he satisfied adult criteria for the metabolic syndrome. In addition, on the
basis of his mild to moderate elevation in aminotransferase levels, morbid obesity, evidence of insulin
resistance and increased echogenicity on hepatic ultrasonography, a presumptive diagnosis of
nonalcoholic fatty liver disease was made. This patient's total cholesterol and HDL cholesterol levels
were both above the 95th
percentile for his age, which further supported the diagnosis of dyslipidemia
that had been established by the low HDL cholesterol and high triglyceride levels. His elevated 2 h
glucose level on a oral glucose test demonstrated impaired glucose tolerance, but not type 2 diabetes
For the treatment of morbid obesity and associated comorbidities, the patient started to attend a
lifestyle-modification program. The program included a nutrition plan that limited his intake of fat to no
more than 30%, saturated fat to no more than 7% and trans-fatty acids to no more than 1% of total
calories. He has been followed up on a monthly basis in the obesity clinic, with rotating visits to a
physician, dietitian, nurse practitioner and exercise physiologist. In the first month of treatment, the
patient achieved his goal of weight maintenance, and by the fourth month, he had lost 8.0 kg, which
decreased his BMI by 2.7 kg/m2
to 49.6 kg/m2
. The typical treatment goal is a 5% reduction in weight
in the first 6 months of therapy, which this patient had already achieved within 4 months. Repeat
laboratory analysis of his lipid levels, insulin, glucose and aminotransferases will also be performed
after 6 months of therapy.
Discussion of Diagnosis
For adults, morbid obesity is generally defined as a BMI of greater than 35 kg/m2
comorbid conditions, or a BMI of 40 kg/m2
with or without comorbidities; this patient had a BMI of 52.3
. Children with BMI values between the 85th
percentiles for their age and sex are
considered overweight, those with BMI values above the 95th
percentile are considered obese, and
those whose BMI values over the 99th
percentile, such as in the patient we describe, are considered
Adult criteria for the metabolic syndrome include increased waist circumference,
elevated blood pressure, elevated triglyceride levels, and low HDL cholesterol level.
All these criteria
were met by this patient. No universally accepted definition of the metabolic syndrome in children
exists, although many criteria have been proposed.
Worldwide prevalence of pediatric obesity has increased at an alarming rate over the past three
decades, which has prompted tremendous concern in the medical, as well as in the lay communities.
US data from the national Health and nutrition examination survey over this time period has
demonstrated an increase in the prevalence of adolescent obesity (BMI >95th
percentile) from 5% in
1963 to 17.4% in the years between 1999 and 2004.
Data for 2003–2006, however, indicate a
prevalence of 16.3%, which seems to indicate that the trend is stabilizing.
Although the vast majority of obese children and adolescents do not have an underlying, organic
etiology for their condition, a variety of genetic syndromes are commonly associated with morbid
obesity. Most of these syndromes, however, are characterized by substantial developmental delay
that limits the patients' awareness of their orexigenic behavior and decreases their adherence to
lifestyle modification. In addition to these behavioral factors, the propensity toward increased BMI in
many of these syndromes is compounded by short stature. In some syndromes, neurologic factors
exist that promote excessive eating or limit satiety, as do metabolic factors that decrease energy
expenditure. In the case described here, the patient was screened for two of these conditions,
Prader–Willi syndrome and MC4R gene mutations, before being referred to the adolescent obesity
Prader–Willi syndrome is the prototypical syndromic form of obesity and is caused by a deletion in the
long arm of chromosome 15 at q11q13. This deletion either occurs in the paternal chromosome or
results from maternal disomy, in which two copies of the maternal chromosome exist, but no paternal
chromosome is present. Characteristic features of this syndrome include hypotonia, mild to moderate
mental retardation, small hands and feet, hypogonadotropic hypogonadism, fair skin and almond-
shaped palpebral fissures. Feeding problems and growth delay might be prominent during infancy,
and obesity develops between 6 months and 6 years of age. Prader–Willi syndrome causes
hyperphagia as well as impaired satiety and decreased energy expenditure.
The disease can be
diagnosed by performing either high-resolution chromosome analysis or fluorescent in situ
hybridization with specific probes.
The product of the MC4R gene is a 333 kD protein that is primarily expressed in the brain and
encoded by a single exon on 18q22. Mutations in this gene are associated with obesity in an
autosomal-dominant fashion, and in one study researchers found anomalies in this gene in 5.8% of
the 500 morbidly obese children who participated.
Unlike almost all other inherited forms of obesity,
MC4R mutations are not associated with mental retardation or growth delay.
The role of genetic screening in obese patients remains to be defined, as increasing numbers of
genes are being identified that are involved in the regulation of energy homeostasis. The vast majority
of these genetic syndromes, however, are characterized by developmental delay and short stature, as
well as by a variety of specific phenotypic characteristics (Table 1). This fact should help caregivers to
weigh the benefit of performing such screens in obese children with normal development and growth
velocity. In addition, knowledge of other defining features of these syndromes can help guide physical
examination and indicate whether further screening for the genetic syndrome is necessary.
By contrast, the usefulness of genetic screening for single-gene mutations that affect specific proteins
important in energy homeostasis, such as those in the MC4R gene, is difficult to ascertain. Unlike
mutations in many of the specific syndromes, these single-gene mutations, as illustrated by those of
MC4R, might not be associated with other phenotypic features. The caregiver's ability to determine
the diagnostic yield of specific genetic testing on the basis of the patient's history and their physical
examination findings is, therefore, limited. Moreover, until specific therapies are developed for
patients with mutations, the clinical usefulness of identification of these conditions might be restricted
to genetic counseling. Given the normal develop mental and growth history in the patient we describe,
in conjunction with the lack of characteristic, phenotypic features on physical examination, detailed
genetic screening would not have been indicated.
Screening for the common comorbidities of obesity, such as dyslipidemia, nonalcoholic fatty liver
disease, hypertension, insulin resistance or diabetes mellitus, is indicated in morbidly obese
adolescents, as outlined in the recent review by the American Academy of Pediatrics Expert
Committee on Childhood Obesity.
Current guidelines for laboratory screening of children with a BMI
that falls above the 95th
percentile seen in the primary-care setting include serum measurements of
fasting glucose, lipids, aspartate aminotransferase and alanine aminotransferase levels.
Indications for further screening might include a family history of any of the above mentioned
comorbidities or increased clinical suspicion for a specific comorbidity (Figure 2). If a patient's blood
pressure is consistently elevated above the 95th
percentile for age, sex and height, use of an
appropriately sized cuff to undertake 24 h ambulatory blood-pressure monitoring would be appropriate,
followed by screening for renal hyper tension by ultrasonography, serum blood urea nitrogen and
creatinine levels, urinalysis and urine culture.
If sleep apnea is suspected on the basis of snoring,
pauses in respiration during sleep, daytime somnolence, secondary enuresis or falling performance in
school, poly somnography might be considered. If nonalcoholic fatty liver disease is suspected,
hepatic ultrasonography is indicated, in addition to laboratory screening for alternative causes of
chronic liver disease, such as α1-antitrypsin deficiency, autoimmune hepatitis, Wilson disease and
viral hepatitis. If type 2 diabetes mellitus is suspected, a 2 h glucose-tolerance test should be
performed. If the patient has goiter or hypothyroidism is clinically suspected, serum levels of TSH,
free T4, antibodies to thyroid peroxidase and to thyroglobulin should be measured.
Figure 2. (click image to zoom) Screening algorithm
for obese children with BMI in the 95th
above. abbreviations: aLt, alanine aminotransferase;
ast, aspartate aminotransferase; BP, blood pressure;
FISH, fluorescence in situ hybridization, NAFLD,
nonalcoholic fatty liver disease.
Treatment and Management
The lifestyle-modification program chosen for this patient targeted specific behaviors identified in his
history that had contributed to his increased total caloric and saturated fat intake, as well as his
decreased levels of physical activity. Motivational interviewing techniques, such as empathy, reflective
listening, setting of agendas and shared decision-making, were incorporated into the initial interview
as well as follow-up visits.
He was asked to keep a log of his daily physical activity for review at follow-up visits and for the
purpose of self-monitoring—a well-validated behavior-modification technique in obesity treatment.
He is scheduled to attend the adolescent obesity clinic once a month. At these visits, adherence to
recommendations are assessed, continued education in nutrition and activity is provided, medical
comorbidities are reassessed, and additional recommendations and goals are agreed upon.
This form of lifestyle modification is individualized to the specific characteristics of the patient and,
therefore, does not lend itself to a standardized, formulaic approach. Rather, it is based on
identification and modification of behaviors that are strongly linked to the development of obesity in
children, such as consumption of sweetened beverages, portion control and limitation of sedentary
behavior (Box 1). Assessment of the patient's self-efficacy and readiness for change, while these
modifiable behaviors are targeted, is the approach to therapy favored in the American Academy of
Pediatrics Expert Committee guidelines, which contains a comprehensive review of the evidence
base behind each of these behaviors.
After 6 months of behavior and lifestyle modification, the patient's progress and comorbidity status will
be re assessed. If the initial goal of 5% reduction in weight is not achieved, or if the severity of the
patient's comorbidities demands more-aggressive management, pharmacologic or surgical therapies
might be considered. Currently, two medications are approved for the treatment of obesity in
adolescents: sibutramine and orlistat. Pediatric trials have been performed on both medications,[12,13]
but their clinical use has been limited by a high out-of-pocket cost to patients. Bariatric surgery—
either gastric bypass
or laparoscopic, adjustable gastric banding
—is increasingly used for the
treatment of adolescent obesity. The patient described here is currently awaiting his 6-month re-
evaluation to determine whether these alternative therapies should be considered, although his
excellent response to lifestyle modification so far argues for continuation of this approach.
As the epidemic of pediatric obesity continues, primary-care physicians are increasingly called upon
to assess and treat this condition and its comorbidities. Achievement of meaningful weight loss
through lifestyle modification is difficult and frustrating for parents and physicians alike, and might
raise suspicion of an underlying genetic condition that results in impaired metabolic homeostasis.
Careful consideration of the family history and developmental history of the child, paired with close
attention to growth parameters and specific phenotypic features revealed during the physical
examination, can reliably exclude the need for specific screenings for genetic obesity in the majority of
obese pediatric patients. Routine screening for common comorbidities of obesity should be performed
and, if any are identified, the patient should be considered for specific treatment of these
comorbidities if he or she fails to respond to dietary and lifestyle modifications.
Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the
content of the learning objectives, questions and answers of the Medscape-accredited continuing
medical education activity associated with this article.
Written consent for publication was obtained from the patient's mother.
RE Kramer, Section of Pediatric Gastroenterology, Hepatology and Nutrition, the Children's Hospital,
University of Colorado Denver, 13123 E. 16th
avenue, B-290, Aurora, CO 80045, USA. Email:
Table 1. Genetic Causes of Obesity
Box 1. Behavioral Targets for Lifestyle Modification
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