Isolated growth hormone deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Isolated growth hormone deficiency is a condition caused by a severe shortage or absence of growth hormone. Growth hormone is a protein that is necessary for the normal growth of the body's bones and tissues. Because they do not have enough of this hormone, people with isolated growth hormone deficiency commonly experience a failure to grow at the expected rate and have unusually short stature. This condition is usually apparent by early childhood.

There are four types of isolated growth hormone deficiency differentiated by the severity of the condition, the gene involved, and the inheritance pattern.

Isolated growth hormone deficiency type IA is caused by an absence of growth hormone and is the most severe of all the types. In people with type IA, growth failure is evident in infancy as affected babies are shorter than normal at birth.

People with isolated growth hormone deficiency type IB produce very low levels of growth hormone. As a result, type IB is characterized by short stature, but this growth failure is typically not as severe as in type IA. Growth failure in people with type IB is usually apparent in early to mid-childhood.

Individuals with isolated growth hormone deficiency type II have very low levels of growth hormone and short stature that varies in severity. Growth failure in these individuals is usually evident in early to mid-childhood. It is estimated that nearly half of the individuals with type II have underdevelopment of the pituitary gland (pituitary hypoplasia). The pituitary gland is located at the base of the brain and produces many hormones, including growth hormone.

Isolated growth hormone deficiency type III is similar to type II in that affected individuals have very low levels of growth hormone and short stature that varies in severity. Growth failure in type III is usually evident in early to mid-childhood. People with type III may also have a weakened immune system and are prone to frequent infections. They produce very few B cells, which are specialized white blood cells that help protect the body against infection (agammaglobulinemia).

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Isolated growth hormone deficiency is caused by mutations in one of at least three genes. Isolated growth hormone deficiency types IA and II are caused by mutations in the GH1 gene. Type IB is caused by mutations in either the GH1 or GHRHR gene. Type III is caused by mutations in the BTK gene.

The GH1 gene provides instructions for making the growth hormone protein. Growth hormone is produced in the pituitary gland and plays a major role in promoting the body's growth. Growth hormone also plays a role in various chemical reactions (metabolic processes) in the body. Mutations in the GH1 gene prevent or impair the production of growth hormone. Without sufficient growth hormone, the body fails to grow at its normal rate, resulting in slow growth and short stature as seen in isolated growth hormone deficiency types IA, IB, and II.

The GHRHR gene provides instructions for making a protein called the growth hormone releasing hormone receptor. This receptor attaches (binds) to a molecule called growth hormone releasing hormone. The binding of growth hormone releasing hormone to the receptor triggers the production of growth hormone and its release from the pituitary gland. Mutations in the GHRHR gene impair the production or release of growth hormone. The resulting shortage of growth hormone prevents the body from growing at the expected rate. Decreased growth hormone activity due to GHRHR gene mutations is responsible for many cases of isolated growth hormone deficiency type IB.

The BTK gene provides instructions for making a protein called Bruton tyrosine kinase (BTK), which is essential for the development and maturation of immune system cells called B cells. The BTK protein transmits important chemical signals that instruct B cells to mature and produce special proteins called antibodies. Antibodies attach to specific foreign particles and germs, marking them for destruction. It is unknown how mutations in the BTK gene contribute to short stature in people with isolated growth hormone deficiency type III.

Some people with isolated growth hormone deficiency do not have mutations in the GH1, GHRHR, or BTK genes. In these individuals, the cause of the condition is unknown. When this condition does not have an identified genetic cause, it is known as idiopathic isolated growth hormone deficiency.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Isolated growth hormone deficiency can have different inheritance patterns depending on the type of the condition.

Isolated growth hormone deficiency types IA and IB are inherited in an autosomal recessive pattern, which means both copies of the GH1 or GHRHR gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Isolated growth hormone deficiency type II can be inherited in an autosomal dominant pattern, which means a mutation in one copy of the GH1 gene in each cell is sufficient to cause the disorder. This condition can also result from new mutations in the GH1 gene and occur in people with no history of the disorder in their family.

Isolated growth hormone deficiency type III, caused by mutations in the BTK gene, is inherited in an X-linked recessive pattern. The BTK gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The incidence of isolated growth hormone deficiency is estimated to be 1 in 4,000 to 10,000 individuals worldwide.

Which doctor should you see?

The suggested department for discussing Isolated growth hormone deficiency is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Isolated growth hormone deficiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.