Insulin-resistance syndrome type A

Insulin-resistance syndrome type A (also known as Type A insulin resistance syndrome or Kahn syndrome) is a rare genetic disorder characterized by severe insulin resistance in the absence of obesity or lipodystrophy. It is caused by mutations in the insulin receptor gene (INSR), which impair the body's ability to respond normally to insulin. This leads to markedly elevated insulin levels (hyperinsulinemia) as the pancreas attempts to compensate for the resistance. The condition predominantly affects females and typically manifests around puberty. Key clinical features include acanthosis nigricans (dark, velvety patches of skin, particularly in body folds such as the neck, axillae, and groin), and signs of hyperandrogenism in females, including hirsutism (excess body hair), acne, menstrual irregularities (oligomenorrhea or amenorrhea), and polycystic ovaries. Affected individuals are usually lean or of normal body weight, which distinguishes this condition from more common causes of insulin resistance. Males may present with fewer obvious signs, though muscle cramps and acanthosis nigricans can occur. The endocrine and metabolic systems are primarily affected. Over time, patients may develop impaired glucose tolerance or overt diabetes mellitus, though this can be difficult to manage because standard insulin therapy is often ineffective due to the underlying receptor defect. Treatment is largely supportive and symptomatic. Metformin and other insulin-sensitizing agents may provide partial benefit. Management of hyperandrogenic symptoms in females may include oral contraceptives or anti-androgen therapies. Recombinant IGF-1 (mecasermin) has been used in some cases to help improve glycemic control. Long-term monitoring for metabolic complications, including diabetes and cardiovascular risk, is essential.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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