• The disease
• Diagnosis
• Treatment options

Definition

Severe primary IGF-1 deficiency (or (S)PIGFD) is a rare condition that causes significant growth failures in children and adolescents, creating physical and psychological disability.

IGF-1 (also called somatomedin C), is a hormone (a protein made of up 70 amino acids) with a very similar structure to insulin). It is produced by the liver and mediates the effects of growth hormone (GH). IGF-1 stimulates the absorption of glucose, fatty acids, and amino acids enabling the body to maintain tissue growth. It is also involved in the development of the nervous system and plays an important role in building up and maintaining bone density.

The characteristic signs of primary IGF-1 deficiency are low concentrations of IGF-1, despite normal levels of growth hormone, and an absence of secondary causes.

Etiology or origins

The deficiency is caused by an anomaly in the GH/IGF-1 pathway, which causes a series of intra-cellular events that begin when the growth hormone attaches to its receptor (mutations in other words) and end with the secretion of IGF-1.

Laron syndrome (first described in 1999 by Laron Z.), a congenital disease caused by mutations in the growth hormone receptor gene (GHR) gene is the most typical form of primary IGF-1 deficiency.

Symptoms and impact on health

The effects of the deficiency vary depending on origin. In Laron syndrome, they include:

• very small stature (-2SD* for primary deficiency and – 3SD for severe primary deficiency),
• distinctive facial appearance, with no growth spurt in puberty,
• obesity,
• hypogonadism (loss of gonad function, absence of hormone secretion and small genitals),
• metabolic anomalies.

The extent and degree of the symptoms vary from one individual to another. The symptoms of other forms of primary IGF-1 deficiency are less pronounced than in Laron syndrome, with less severe anatomical, morphological, and physiological characteristics, and no genetic abnormality.

Incidence

SIGFD is very rare with an incidence of less than one in 10,000. Studies put the prevalence at between 1.2% and 11%.