Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217

Congenital leptin deficiency - LEP gene
The congenital deficiency of leptin is a process associated with severe obesity from the first months of life. Affected people are normal weight at birth, but they are constantly hungry and gain weight quickly. Without treatment, hunger continues with excessive overeating that causes obesity. From early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children for food, hoarding and eating in secret. People with congenital leptin deficiency also have hypogonadotropic hypogonadism due to reduced production of hormones that direct sexual development. Without treatment, affected individuals have a delayed puberty or do not go through puberty, and may be infertile.
Congenital leptin deficiency is due to mutations in the LEP gene (leptin), located on the long arm of chromosome 7 (7q31.3), which encodes a hormone called leptin, involved in the regulation of body weight. Usually, adipocytes release leptin in proportion to their size. As fat accumulates in the cells, more leptin is produced. This increase in leptin indicates that fat stores are increasing. Leptin aggregates bind and activate the leptin receptor. The leptin receptor protein is found on the cell surface in many organs and tissues of the body, including the hypothalamus. The hypothalamus controls hunger and thirst, as well as other functions such as sleep, mood, and body temperature. It also regulates the release of hormones that have many functions throughout the body. In the hypothalamus, the binding of leptin to its receptor triggers a series of chemical signals that affect the feeling of hunger and help produce a feeling of satiety.
At least 7 mutations in the LEP gene have been identified in individuals with congenital leptin deficiency. Mutations in the LEP gene inhibit leptin synthesis. As a consequence, there is no signaling that triggers the sensation of satiety, which causes the weight gain and excessive hunger associated with this disease. Because hypogonadotropic hypogonadism occurs in congenital leptin deficiency, it is believed that leptin signaling is also involved in the regulation of the hormones that drive sexual development. However, the details of this intervention and how it can be modified in congenital leptin deficiency are unknown.
This disease is inherited with an autosomal recessive pattern, i.e. both copies of the gene in each cell must have the mutations for the alteration to be expressed. Parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Congenital Leptin Deficiency, by means of the complete PCR amplification of the exons of the LEP gene, respectively, and their subsequent sequencing.
Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).