Congenital Leptin Deficiency

What is congenital leptin deficiency?

Congenital leptin deficiency is a rare condition that causes severe obesity, usually beginning in the first few months after birth. This obesity is a result of extreme hunger, a symptom of the condition. Congenital leptin deficiency is extremely rare; only a few dozen cases have been reported.

What are the symptoms of congenital leptin deficiency?

• Extreme hunger
• Excessive eating
• Severe obesity
• Abnormal eating habits (hoarding, eating in secret)
• Hypogonadotropic hypogonadism, affecting sexual development
• Delayed puberty
• Infertility

What causes congenital leptin deficiency?

Congenital leptin deficiency is caused by mutations in the LEP gene, whose role is to provide instructions for making leptin, which is involved in the regulation of body weight. Normally, fat cells release leptin in proportion to their size. As fat accumulates in cells, more leptin is produced. LEP gene mutations therefore lead to an absence of leptin. This therefore results in the feelings of satiety to not occur, leading to the excessive hunger and weight gain. And because hypogonadotropic hypogonadism occurs in congenital leptin deficiency, researchers suggest that leptin signaling is also involved in regulating the hormones that control sexual development. However, the specifics of this involvement are unknown.

How is congenital leptin deficiency diagnosed?

Family history, severe hyperphagia, and early-onset obesity may lead to suspicion of a monogenic obesity syndrome. The diagnosis of congenital leptin deficiency can be confirmed by analysis of serum leptin levels or identification of mutations in the ob gene. Congenital leptin deficiency is often diagnosed after clinical evaluation, detailed patient history, and identification of characteristic symptoms.  A diagnosis may be confirmed through:

• Analysis of serum leptin levels
• Identification of mutations in the ob gene

What are the treatments for congenital leptin deficiency?

Congenital leptin deficiency can be treated with daily subcutaneous injections of recombinant human leptin (leptin replacement therapy).

Where can I find out more about congenital leptin deficiency?

• NIH
• Orphanet