A 19-Year-Old Man With Life-Threatening Obesity

Shahida Badsha, MBBS, FCPS, MCPS


April 09, 2018

Infants with Prader-Willi syndrome present with hypotonia and difficulty feeding due to poor sucking and swallowing reflexes. Failure to thrive can ensue. Typically, an insatiable appetite and chronic food-seeking behaviors (hyperphagia) begin in the preschool years, leading to excessive weight gain. Satiety and energy balance are mainly controlled by the hypothalamus; however, numerous regions in the nervous system play a role. Ghrelin, a 28-amino acid peptide, produced in the stomach, is potentially the hormone responsible for causing obesity in individuals with Prader-Willi syndrome.

Children with Prader-Willi syndrome typically have mild-to-moderate intellectual impairment and learning disabilities. Vision problems, such as strabismus and near-sightedness, are common. Behavioral problems are also common, such as temper outbursts, stubbornness, and obsessive-compulsive behaviors described as picking at the skin and skin lesions. Phenotypic features include craniofacial features described as a pear-shaped face with a narrow forehead and almond-shaped eyes, downturned corners to the mouth with a thin upper lip, underdeveloped genitalia, hypogonadism, and small hands and feet. Hypogonadism can be of hypothalamic origin or due to primary gonadal failure.[3,4,5] Puberty is delayed or incomplete. Scoliosis can be a concern.

Patients with Prader-Willi syndrome have short stature, and their bone age lags behind their chronological age. Short stature is an important characteristic of Prader-Willi syndrome; these children do not have a growth spurt at pubertal age. This lack of height growth is contrary to exogenous obesity, in which height is gained in the prepubertal and postpubertal years. Growth hormone can help children with Prader-Willi syndrome to normalize height, increase lean body mass and mobility, and decrease fat mass. Structured behavioral modification approaches have also helped these patients with weight management.

Morbidity and mortality in Prader-Willi syndrome are related to life-threatening morbid obesity and its associated comorbidities.[2,6,7] These patients are prone to develop type 2 diabetes. Poor circulation can lead to stasis dermatitis nodosum. Other skin lesions have also been reported in association with Prader-Willi syndrome.[8,9] Sleep abnormalities are common. Patients are at high risk of developing sleep-disordered breathing (obstructive sleep apnea) and cor pulmonale due to the comorbidities associated with morbid obesity.[10,11]

Bardet-Biedl syndrome is a genetic condition characterized with syndromic central obesity. Common features include learning disabilities, retinitis pigmentosa, hypogonadism, postaxial polydactyly, and structural or functional renal abnormalities. Bardet-Biedl syndrome is inherited as an autosomal recessive trait and can result from mutations in at least 14 different genes, called BBS genes. These mutations lead to abnormal structure and function of cilia. About 25% of all cases of BBS result from mutations in the BBS1 gene; 20% are caused by mutations in the BBS10 gene. The remaining BBS genes account for a small percentage of cases. In 25% of patients diagnosed with BBS, the cause is unknown. Diagnosis is usually based on clinical findings and is confirmed by gene sequencing. No definitive treatment is available. Multidisciplinary surveillance is important to control symptoms and complications.[12,13,14]

Cushing syndrome involves a combination of clinical features that result from prolonged exposure to excess cortisol, either exogenous or endogenous. Exogenous Cushing syndrome is often iatrogenic and is caused by administration of glucocorticoids used to treat medical disorders. Endogenous Cushing syndrome is divided into two types: ACTH-dependent and ACTH-independent. The most common ACTH-dependent disease is due to pituitary adenoma. Endogenous ACTH-independent disease is due to ACTH-producing tumors in the chest (eg, small cell lung carcinoma, bronchial and thymic carcinoids, medullary thyroid carcinoma, or other conditions that ectopically produce ACTH (eg, gastroenteropancreatic neuroendocrine tumors, pheochromocytoma).[15] In this case, although the patient had received oral steroids for his skin condition, neither his clinical features nor his laboratory results suggest Cushing syndrome.

Pseudohypoparathyroidism, or Albright hereditary osteodystrophy, is characterized by parathyroid hormone-resistant hypocalcemia and hyperphosphatemia, combined with developmental and skeletal defects. Patients present with short stature, obesity, rounded face, dental hypoplasia, shortened fourth metacarpals, and soft tissue calcification or ossification. Pseudohypoparathyroidism is diagnosed by measuring the sera levels of calcium, phosphorus, and parathyroid hormone. A mutation identified in the GNAS1 gene is confirmatory.[16] This patient had normal calcium and phosphate levels.


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