Table 3.
States of Leptin Deficiency and Leptin Resistance1
| Syndrome | Estimated Prevalence | Associated Features |
|---|---|---|
| Obesity associated with leptin deficiency | ||
| Complete congenital leptin deficiency | Rare | Early-onset morbid obesity, profound hyperphagia, hyperinsulinemia and type II diabetes, hypogonadotrophic hypogonadism, advanced bone age, immune dysfunction [62] |
| Heterozygous leptin deficiency | Unknown | Obesity with significantly lower than expected serum leptin levels with respect to % body fat, normal neuroendocrine function [62] |
| Fat loss associated with leptin deficiency | ||
| Congenital generalized lipoatrophy | Rare | Generalized fat wasting, impaired glucose tolerance, insulin resistance/type II diabetes, hepatic steatosis, acanthosis nigricans [138] |
| HAART-induced lipoatrophy | 15-36% of HIV-infected patients [107] | Fat wasting of the face, arms, legs, and buttocks; hypertriglyceridemia, impaired glucose tolerance, insulin resistance/type II diabetes, hepatic steatosis [138] |
| Hypothalamic amenorrhea (functional) | Up to 69% of trained female athletes [166]; 7.6% in women aged 15-24, 3.0% in women aged 25-34, and 3.7% in women aged 35-44 years [243] | Psychogenic stress, strenuous exercise, reduced fat mass, osteoporosis, amenorrhea with decreased GnRH pulsatility and estradiol levels, decreased thyroid hormone levels, increased growth hormone levels, and decreased IGF-1 [31] |
| Obesity associated with leptin resistance | ||
| Leptin receptor deficiency | Rare | Phenotype similar to congenital leptin deficiency with early-onset obesity, hyperphagia but less remarkable hyperinsulinemia. In addition, exhibit hypogonadotrophic hypogonadism, mild growth retardation, hypothalamic hypothyroidism [38] |
| POMC deficiency | Rare | Early-onset obesity, hyperphagia, ACTH deficiency with adrenal insufficiency/crisis, pale skin and red hair from lack of MSH function at MC1Rs [118] |
| MC4R deficiency | 0.5% of obese adults [57], 6% of early-onset, severe obesity [60] | Early-onset obesity, hyperphagia, increased lean mass, increased linear growth, and severe hyperinsulinemia [60] |
| Prohormone convertase 1 deficiency | Rare | Early-onset severe obesity, abnormal glucose homeostasis, hypoinsulinemia, hypogonadotropic hypogonadism, hypocortisolism [106] |
| Neurotrophin receptor tropomyosin-related kinase B mutations | Rare | BDNF deficiency resulting in severe obesity, hyperphagia, developmental delay, and cognitive dysfunction [57] |