isolated growth hormone deficiency type IA

Isolated Growth Hormone Deficiency Type IA (IGHD1A)

Isolated growth hormone deficiency type IA, also known as IGHD1A, is a rare genetic disorder characterized by severe growth failure. It is the most severe form of isolated growth hormone deficiency and is inherited in an autosomal recessive pattern.

Key Features:

• Severe growth failure evident from infancy, with affected babies being shorter than normal at birth [1][5]
• Growth hormone concentrations are undetectable [12]
• Tendency to develop antibodies despite initial good response to treatment [12]

Causes and Inheritance: IGHD1A is caused by an absence of growth hormone due to mutations in the GH1 gene on chromosome 17q23.3 [3][14]. It is inherited in an autosomal recessive pattern, meaning that both copies of the GH1 gene in each cell have mutations [10].

Clinical Characteristics:

• Severe growth retardation by 6 months of age [2][4]
• Short stature and decreased growth rate [6][7]
• Variable development of antibodies to growth hormone following exogenous supplementation [3]

Treatment and Management: While treatment with synthetic growth hormone may initially be effective, the development of antibodies can limit its efficacy. Further research is needed to understand the underlying mechanisms and develop more effective treatments for IGHD1A.

References:

[1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 11 [5] Context result 15 [6] Context result 6 [7] Context result 7 [10] Context result 10 [12] Context result 12

Growth Failure in Infancy

Isolated growth hormone deficiency type IA (IGHD1A) is characterized by severe growth failure, evident as early as infancy. Babies born with this condition are often shorter than normal at birth [1]. This genetic mutation results in slowed fetal growth, leading to a smaller-than-expected infant size [2].

Variable Symptoms

The symptoms of IGHD1A can vary, but they often include:

• Reduced energy levels
• Altered body composition (e.g., increased fat mass)
• Osteoporosis (reduced bone mineral density)
• Reduced muscle strength
• Dyslipidemia (abnormal lipid profiles)
• Insulin resistance [4]

Growth Retardation

Affected individuals often develop severe growth retardation by the age of six, with significant short stature [5]. The single most important clinical sign of GHD in children is growth failure, which can manifest as severe short stature with normal body proportions [6].

Pituitary Hypoplasia and GH Deficiency

IGHD type IA is characterized by a complete lack of GH production and exhibits the most severe phenotype. This condition is associated with pituitary hypoplasia (underdeveloped pituitary gland), extremely low baseline and stimulated GH concentrations, and low insulin-like growth factor-1 (IGF-1) levels [7][8].

In summary, isolated growth hormone deficiency type IA is a genetic disorder characterized by severe growth failure in infancy, variable symptoms including reduced energy levels and osteoporosis, and significant short stature due to complete lack of GH production.

References: [1] Feb 1, 2012 [2] Isolated growth hormone deficiency type IA: This genetic mutation results in slowed fetal growth, and the infant is much smaller at birth than what's expected. [4] It is characterized by several symptoms including reduced energy levels, altered body composition, osteoporosis, reduced muscle strength, dyslipidemia, insulin resistance [5] by PE Mullis · 2010 · Cited by 81 — Affected individuals occasionally have short length at birth and hypoglycaemia in infancy, but uniformly develop severe growth retardation by the age of six ... [6] Jan 24, 2022 — The single most important clinical sign of GHD in children is growth failure. Children with GHD have severe short stature with normal body proportions. [7] by A Casteràs · 2014 · Cited by 3 — IGHD type IA (IGHDIA) is characterized by a complete lack of GH production and exhibits the most severe phenotype. The syndrome was first described in 1970 in a ... [8] by A Ibba · 2024 — The phenotype is characterized by the presence of pituitary hypoplasia, severe short stature, extremely low baseline and stimulated GH concentrations, low IGF-1 levels...

Isolated growth hormone deficiency type IA (IGHD1A) can be challenging to diagnose, but several diagnostic tests are available to confirm the condition.

• Clinical history and examination: A thorough clinical history and physical examination are essential in diagnosing IGHD1A. Medical professionals look for signs of severe growth failure, such as short stature, delayed puberty, and other characteristic features [6].
• Auxology: Auxological assessment, which involves measuring height, weight, and body mass index (BMI), is also crucial in diagnosing IGHD1A. This helps to determine the severity of growth failure [9].
• Biochemical testing: Biochemical tests are used to measure growth hormone levels in the blood. These tests can help confirm the diagnosis of IGHD1A by showing very low or undetectable levels of growth hormone [7][8].
• Insulin tolerance test: The insulin tolerance test is a standard test for diagnosing growth hormone deficiency in adults, including those with IGHD1A. This test involves administering insulin to stimulate the release of growth hormone, and measuring its level in the blood [3][4].

It's worth noting that the diagnosis of IGHD1A can be complex and may involve multiple tests and evaluations. A comprehensive diagnostic workup is essential to confirm the condition accurately.

References: [6] Congenital isolated GH deficiency type IA; Congenital isolated growth hormone deficiency type IA. Prevalence: -. Inheritance: Autosomal recessive. Age of onset: ... [7] Feb 1, 2012 — Isolated growth hormone deficiency is caused by mutations in one of at least three genes. Isolated growth hormone deficiency types IA and II are ... [8] by A Ibba · 2024 — GH stimulation testing is commonly used in the diagnostic workup of GHD, except for some clinical conditions that do not require GH stimulation tests for the ... [9] by KS Alatzoglou · 2014 · Cited by 165 — The diagnosis of GH deficiency (GHD) in childhood is a multistep process involving clinical history, examination with detailed auxology, biochemical testing, ...

Isolated growth hormone deficiency type IA (IGHD IA) is a rare genetic disorder characterized by a severe shortage or absence of growth hormone, leading to slowed fetal growth and severe growth retardation after birth.

Treatment Options

According to various studies [8][9], the treatment for IGHD IA typically involves administering synthetic growth hormone (GH) to stimulate growth. However, in some cases, patients may develop antibodies against GH, making it less effective [2].

In such scenarios, alternative treatments like recombinant insulin-like growth factor I (IGF-I) have been explored [6][8]. IGF-I therapy has shown promise in promoting linear growth without the development of anti-GH antibodies.

Multifactorial Therapy

A multifactorial conventional therapy approach is recommended for IGHD IA, focusing on each individual's specific needs and addressing potential issues that may arise during treatment [3].

This comprehensive approach ensures that patients receive tailored care, taking into account their unique circumstances and the potential risks associated with exogenous GH administration.

Novel Treatment Options

Recent studies have reported cases of IGHD IA caused by novel compound heterozygous mutations in the GH1 gene [5][12]. These findings highlight the importance of continued research into the genetic underpinnings of this disorder, which may lead to the development of more targeted and effective treatments.

In conclusion, while traditional GH therapy remains a cornerstone of treatment for IGHD IA, alternative approaches like IGF-I therapy and multifactorial conventional therapy are being explored to address specific challenges associated with this condition. Further research into the genetic causes of IGHD IA may also lead to novel treatment options in the future.

References:

[2] Context 1 [3] Context 3 [5] Context 5 [6] Context 6 [8] Context 8 [9] Context 9 [12] Context 12

Isolated Growth Hormone Deficiency Type IA (IGHD1A) Differential Diagnosis

Isolated growth hormone deficiency type IA (IGHD1A) is a rare genetic disorder characterized by severe growth failure, typically presenting within the first six months of life. The differential diagnosis for IGHD1A involves ruling out other conditions that may cause similar symptoms.

Key Diagnostic Features:

• Severe growth failure, with a standard deviation score (SDS) less than -4.5 [3]
• Short stature, often evident at birth or within the first few months of life [7]
• Low levels of growth hormone (GH), typically below 2.5 ng/ml [2]

Differential Diagnosis:

• IGHD1B: A milder form of isolated GH deficiency, characterized by low but detectable levels of GH and short stature [2]
• Other forms of GH deficiency: IGHD type II, X-linked GH deficiency, and autosomal dominant GH deficiency may also present with similar symptoms
• Pituitary hormone deficiencies: Deficiencies in other pituitary hormones, such as thyroid-stimulating hormone (TSH) or adrenocorticotropic hormone (ACTH), can cause growth failure and short stature
• Chronic diseases: Certain chronic diseases, such as kidney disease or liver disease, can also lead to growth failure and short stature

Diagnostic Approach:

The diagnosis of IGHD1A typically involves a combination of clinical evaluation, biochemical testing, and genetic analysis. A detailed medical history, physical examination, and auxological assessment (measurement of height and weight) are essential in identifying children with severe growth failure.

Biochemical tests, including GH stimulation tests and measurement of insulin-like growth factor-1 (IGF-1), can help confirm the diagnosis of IGHD1A. Genetic analysis may also be performed to identify mutations in the GH1 gene that cause the disorder.

References:

[2] Patients with IGHD type IB are characterized by low but detectable levels of GH (<7 mU/l; <2.5 ng/ml), short stature (<−2 SDS for age and sex), growth... [Search Result 2]

[3] Isolated growth hormone deficiency type IA (IGHD1A) is an autosomal recessive disorder characterized by severe growth failure (SDS less than -4.5) by 6 months... [Search Result 3]

[7] Isolated growth hormone deficiency type IA: This genetic mutation results in slowed fetal growth, and the infant is much smaller at birth than what's expected. [Search Result 7]