congenital leptin deficiency

Congenital Leptin Deficiency: A Rare Genetic Disorder

Congenital leptin deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the leptin gene [12]. This condition is characterized by severe early-onset obesity, marked hyperphagia (intense drive to eat), and impaired satiety (feeling full) [4][9].

Key Features:

• Severe obesity beginning in the first few months of life [3][10]
• Constant hunger and rapid weight gain [10][14]
• Delayed puberty [13]
• Frequent bacterial infections [13]

Causes: Congenital leptin deficiency is caused by genetic mutations, also known as pathogenic variants, in the leptin gene. These mutations can be hereditary or occur spontaneously [11].

Treatment: Targeted therapy with recombinant human leptin (metreleptin) has been shown to result in dramatic weight loss and metabolic improvements [14]. However, metreleptin's only FDA-approved indication is for the treatment of congenital leptin deficiency.

References:

[1] Congenital leptin deficiency is diagnosed based on a clinical examination, symptoms, and laboratory and genetic testing results. (Search result 1) [2] Congenital leptin deficiency is a form of monogenic obesity characterized by severe early-onset obesity and marked hyperphagia. (Search result 2) [3] Congenital leptin deficiency is a condition that causes severe obesity beginning in the first few months of life. (Search result 3) [4] Lack of appropriate leptin signaling manifests in an intense drive to eat (hyperphagia), impaired satiety, and severe early-onset obesity. (Search result 4) [5] Congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity. (Search result 5) [6] The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance. (Search result 6) [7] Congenital leptin deficiency due to a mutation in the leptin gene and/or the leptin receptor gene is associated with a significant delay in growth in early childhood. (Search result 7) [8] Congenital leptin deficiency results from loss of function mutations of the LEP gene, which encodes for the leptin protein. (Search result 8) [9] Characteristic features include hyperphagia, obesity, hypogonadism, and impaired T-cell–mediated immunity. Treatment with recombinant human leptin has been shown to be effective. (Search result 9) [10] Congenital leptin deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. (Search result 10) [11] Obesity due to congenital leptin deficiency is caused by genetic mutations, also known as pathogenic variants. Genetic mutations can be hereditary or occur spontaneously. (Search result 11) [12] Congenital leptin deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the leptin gene. This review describes the molecular and cellular characteristics of the eight distinct mutations found so far in humans. (Search result 12) [13] Without leptin, your body thinks it has no body fat, which then signals intense, uncontrolled hunger and food consumption. Because of this, congenital leptin deficiency results in class III obesity in children and delayed puberty. It’s also associated with frequent bacterial infections. (Search result 13) [14] Background: Congenital leptin deficiency (CLD) is a rare autosomal recessive form of monogenic obesity caused by loss-of-function mutations in the leptin gene. Targeted therapy is available in the form of recombinant human leptin (metreleptin). Previous case series have reported dramatic weight loss and metabolic improvements with treatment, but metreleptin’s only FDA-approved indication is for the treatment of congenital leptin deficiency. (Search result 14) [15] Congenital leptin deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. Without treatment, the extreme hunger continues and leads to chronic ... (Search result 15)

Severe Obesity Beginning in Infancy

Congenital leptin deficiency is a rare genetic condition that causes severe obesity beginning in the first few months of life [10]. Affected individuals are typically of normal weight at birth, but they quickly gain weight due to constant hunger and excessive eating (hyperphagia) [6].

Key Signs and Symptoms:

• Severe early-onset obesity
• Constant hunger and excessive eating (hyperphagia)
• Rapid weight gain in the first few months of life
• Normal weight at birth, but quickly gaining weight thereafter

These symptoms are often associated with a significant delay in growth in early childhood [8]. It's essential to note that not all individuals with congenital leptin deficiency will show signs and symptoms of the condition

Diagnostic Tests for Congenital Leptin Deficiency

Congenital leptin deficiency can be diagnosed through various tests, which are essential for confirming the condition and ruling out other possible causes of severe obesity in infants. Here are some diagnostic tests used to diagnose congenital leptin deficiency:

• Genetic Testing: Genetic testing is a crucial step in diagnosing congenital leptin deficiency. It involves analyzing the ob gene to identify mutations that can cause the condition [4]. This test can confirm whether an individual has inherited two copies of the mutated gene, one from each parent.
• Leptin Blood Test: A blood test can check the amount of leptin in a blood sample taken from a vein in your arm. This test measures leptin levels and can help diagnose congenital leptin deficiency [7].
• Clinical Examination and Symptoms: Diagnosis is also based on a clinical examination, symptoms, and the results of genetic testing [1][9]. A healthcare provider will assess an individual's overall health, medical history, and physical characteristics to determine if they have congenital leptin deficiency.
• Next-Generation Sequencing (NGS) Test: An NGS test is a next-generation sequencing (NGS) test appropriate for individuals with clinical signs and symptoms, suspicion of, or family history of Congenital Leptin Deficiency [3]. This test can identify genetic mutations that cause the condition.

These diagnostic tests are essential for confirming congenital leptin deficiency and developing an effective treatment plan. Early diagnosis and intervention can significantly improve outcomes for individuals with this condition.

References:

[1] Mar 9, 2023 — This condition is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms and the results of genetic testing [1]. [3] This is a next generation sequencing (NGS) test appropriate for individuals with clinical signs and symptoms, suspicion of, or family history of Congenital Leptin Deficiency [3]. [4] The diagnosis of congenital leptin deficiency can be confirmed by analysis of serum leptin levels or identification of mutations in the ob gene [4]. [7] What test measures leptin levels? A blood test can check the amount of leptin in a blood sample taken from a vein in your arm [7]. [9] Feb 21, 2023 — Diagnosis is based on a clinical examination, symptoms and the results of genetic testing [9].

Treatment Options for Congenital Leptin Deficiency

Congenital leptin deficiency is a rare genetic disorder characterized by the absence or low levels of leptin, a hormone essential for regulating energy balance and body weight. Fortunately, various treatment options are available to manage this condition.

• Leptin Replacement Therapy: This involves administering recombinant human leptin (metreleptin) through daily subcutaneous injections. Studies have shown that this therapy can improve or normalize most of the phenotypes associated with congenital leptin deficiency, including hyperphagia, body weight, and hypothalamic dysfunction [1][2].
• Metreleptin: This is a human leptin analog used to treat the symptoms of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. Metreleptin has been shown to improve glycemic control and decrease triglyceride levels in patients with lipodystrophy and leptin deficiency [3].
• Setmelanotide: This is a drug that can be used to treat congenital leptin receptor (LEPR) deficiency, which is another form of leptin-related disorder. With treatment, people with LEPR deficiency develop

Congenital Leptin Deficiency Differential Diagnosis

Congenital leptin deficiency is a rare genetic disorder characterized by severe early-onset obesity, hyperphagia (excessive hunger), and other metabolic disturbances. When considering the differential diagnosis for this condition, several factors should be taken into account.

• Severe Obesity: Children with congenital leptin deficiency often exhibit severe obesity before one year of age [2]. This is a key factor in differentiating this condition from other causes of childhood obesity.
• Hyperphagia: Excessive hunger and abnormal behaviors related to food are common symptoms of congenital leptin deficiency [2].
• Hypogonadotropic Hypogonadism: Leptin plays a crucial role in regulating reproductive function. Congenital leptin deficiency can lead to hypogonadotropic hypogonadism, characterized by low sex hormone levels and delayed puberty [6][8].
• Neuroendocrine/Metabolic Disturbances: The condition is also associated with changes in thyroid and IGF (Insulin-like Growth Factor) axes, indicating broader metabolic disturbances [6][8].

In the differential diagnosis of congenital leptin deficiency, it's essential to consider other conditions that may present with similar symptoms. These include:

• Congenital Leptin-Receptor Deficiency: This condition is characterized by severe obesity and hyperphagia, but it also involves defects in leptin signaling [3][4].
• Other Genetic Disorders: Certain genetic disorders, such as Prader-Willi syndrome or Bardet-Biedl syndrome, can present with similar symptoms of early-onset obesity and metabolic disturbances.

To accurately diagnose congenital leptin deficiency, a comprehensive evaluation of the child's medical history, physical examination, and laboratory tests (including leptin levels) is necessary. Consultation with a geneticist or an endocrinologist may also be helpful in differentiating this condition from other causes of childhood obesity.

References:

[1] Blüher S et al. (2009) Congenital leptin deficiency is associated with a morbidly obese phenotype and significant disturbances in metabolic and immune functions [1].

[2] Feb 21, 2023 - Most people with this condition are obese before one year of age [2].

[3] Farooqi IS et al. (2007) Congenital leptin-receptor deficiency should be considered in the differential diagnosis in any child with hyperphagia and severe obesity [3].

[4] Congenital leptin-receptor deficiency should be considered in the differential diagnosis in any child with hyperphagia and severe obesity [4].

[5] Salum KCR et al. (2021) Here, we review cases of congenital leptin deficiency and the possible beneficial effects of leptin replacement therapy [5].

[6] Leptin deficiency or dysfunction (LEPD) is characterized by severe early-onset obesity, hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine/metabolic disturbances [6].

[7] The authors conclude that congenital leptin-receptor deficiency should be considered in the differential diagnosis of all patients with early-onset obesity [7].

[8] Chan JL et al. (2006) Congenital complete leptin deficiency (3–5) or acute hypoleptinemia to <1 ng/ml in leptin-replete humans induces changes in reproductive, thyroid, and IGF axes [8].