Obesity due to congenital leptin deficiency: Difference between revisions
No edit summary |
|||
| Line 3: | Line 3: | ||
==Overview<ref>http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=66628</ref>== | ==Overview<ref>http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=66628</ref>== | ||
Congenital leptin deficiency is a form of monogenic obesity characterised by severe early-onset obesity and marked hyperphagia. | Congenital leptin deficiency is a form of monogenic obesity characterised by severe early-onset obesity and marked hyperphagia. | ||
==Pathophysiology== | |||
Leptin is an adipocyte-derived hormone that plays an important role in energy balance and appetite suppression. Whilst the majority of obese patients display hyperleptinaemia, patients with congenital leptin deficiency have undetectable levels of leptin in the serum. This absence of serum leptin is caused by homozygous frameshift or missense mutations in the ob gene (7q31.3) and is inherited as an autosomal recessive trait. However, a similar phenotype has been observed in three individuals from one consanguineous family who carried homozygous mutations in the gene encoding the leptin receptor (LEPR, 1p31). | |||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
It has been described in less than 30 patients. | It has been described in less than 30 patients. | ||
==Natural history, Complications and Prognosis== | |||
The prognosis for patients undergoing treatment appears to be excellent. However, misdiagnosed patients are at risk of developing the complications normally associated with severe [[obesity]] (in particular type 2 [[diabetes]]), with the prognosis being hampered further by an increased rate of mortality due to childhood infection. | |||
==Diagnosis== | ==Diagnosis== | ||
*Patients with congenital leptin deficiency are severely hyperphagic from early infancy and, although birthweight is normal, they rapidly become obese during early childhood. | *Patients with congenital leptin deficiency are severely hyperphagic from early infancy and, although birthweight is normal, they rapidly become obese during early childhood. | ||
| Line 15: | Line 18: | ||
*Hypogonadotropic [[hypogonadism]] leading to a failure to undergo puberty. | *Hypogonadotropic [[hypogonadism]] leading to a failure to undergo puberty. | ||
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. | |||
==treatment== | |||
Congenital leptin deficiency can be successfully treated with daily subcutaneous injections of recombinant human leptin, resulting in sustained positive effects on weight loss, reducing appetite, appropriate pubertal development and hyperinsulinaemia. | |||
As a result, the prognosis for patients undergoing treatment appears to be excellent. However, misdiagnosed patients are at risk of developing the complications normally associated with severe obesity (in particular type 2 diabetes), with the prognosis being hampered further by an increased rate of mortality due to childhood infection. | |||
==References== | ==References== | ||
Revision as of 19:17, 29 July 2012
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assosciate Editor(s)-In-Chief: Prashanth Saddala M.B.B.S
Overview[1]
Congenital leptin deficiency is a form of monogenic obesity characterised by severe early-onset obesity and marked hyperphagia.
Pathophysiology
Leptin is an adipocyte-derived hormone that plays an important role in energy balance and appetite suppression. Whilst the majority of obese patients display hyperleptinaemia, patients with congenital leptin deficiency have undetectable levels of leptin in the serum. This absence of serum leptin is caused by homozygous frameshift or missense mutations in the ob gene (7q31.3) and is inherited as an autosomal recessive trait. However, a similar phenotype has been observed in three individuals from one consanguineous family who carried homozygous mutations in the gene encoding the leptin receptor (LEPR, 1p31).
Epidemiology and Demographics
It has been described in less than 30 patients.
Natural history, Complications and Prognosis
The prognosis for patients undergoing treatment appears to be excellent. However, misdiagnosed patients are at risk of developing the complications normally associated with severe obesity (in particular type 2 diabetes), with the prognosis being hampered further by an increased rate of mortality due to childhood infection.
Diagnosis
- Patients with congenital leptin deficiency are severely hyperphagic from early infancy and, although birthweight is normal, they rapidly become obese during early childhood.
- An increased susceptibility to infections has also been reported in these infants and appears to be associated with reduced numbers of circulating CD4+ T cells, and impaired T cell proliferation and cytokine release.
Other features of the disorder include
- Hyperinsulinaemia
- Advanced bone age
- Hypothalamic hypothyroidism
- Hypogonadotropic hypogonadism leading to a failure to undergo puberty.
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.
treatment
Congenital leptin deficiency can be successfully treated with daily subcutaneous injections of recombinant human leptin, resulting in sustained positive effects on weight loss, reducing appetite, appropriate pubertal development and hyperinsulinaemia.
As a result, the prognosis for patients undergoing treatment appears to be excellent. However, misdiagnosed patients are at risk of developing the complications normally associated with severe obesity (in particular type 2 diabetes), with the prognosis being hampered further by an increased rate of mortality due to childhood infection.