The portal for rare diseases and orphan drugs

It is a rare disorder of unknown prevalence.

It is generally diagnosed in young women with marked signs of hyperandrogenism, but insulin resistance and acanthosis nigricans may be observed in men and in childhood. Acromegaloid facies or muscular cramps are sometimes associated. Hyperinsulinemia, a biological marker for insulin resistance, is often associated with glucose tolerance defects over the course of the disease, and diabetes progressively sets in. Hyperandrogenism (associated with polycystic ovarian syndrome (see this term) or ovarian hyperthecoses) leads to fertility problems.

In some cases, the syndrome is caused by heterozygous mutations in the insulin receptor gene (INSR; 19p13.3-p13.2), affecting the region encoding the tyrosine kinase domain. Cases associated with homozygous mutations affecting the insulin-binding domain of the receptor have also been reported. However, only 15 to 20% of female patients with hyperandrogenism, insulin resistance and acanthosis nigricans present mutations in the insulin receptor gene. When such mutations are not found, the disease is of unknown cause and may be considered as an HAIR-AN syndrome (see this term).

The differential diagnosis includes the other forms of extreme insulin-resistance, in particular the lipodystrophy syndromes (see these terms), in which the reparation anomaly of the adipose tissue may be clinically minor. The differential diagnosis with type B insulin resistance syndrome is based on the lack of insulin anti-receptor auto-antibodies in patients with the type A syndrome.

Transmission is autosomal dominant.

The treatment consists of dietary changes and/or drugs (metformin, glitazones, or other antidiabetic drugs) to reduce the insulin resistance and treat the diabetes.