Donohue Syndrome (Leprechaunism)
Also known as: Leprechaunism, Insulin Resistance Syndrome Type A, INSR-Related Severe Insulin Resistance
Donohue syndrome, also known as leprechaunism, is a rare genetic disorder characterized by extreme insulin resistance, growth retardation, and distinctive facial features. It is caused by mutations in the INSR gene, which provides instructions for making the insulin receptor. This receptor is essential for insulin to regulate glucose levels in the body. Affected individuals typically have severe feeding difficulties, developmental delays, and a shortened lifespan.
Imagine your body has trouble using sugar from food because the key (insulin) doesn't fit the lock (insulin receptor) properly. This makes it hard to grow and stay healthy, and kids with this problem need special help eating and staying strong.
Signs & Symptoms
- Severe insulin resistance
- Growth retardation
- Failure to thrive
- Decreased subcutaneous fat
- Enlarged clitoris or small penis
- Thickened skin (acanthosis nigricans)
- Full lips
- Large, low-set ears
- Prominent eyes
- Hirsutism (excessive hair growth)
- Developmental delay
- Feeding difficulties
- Hypoglycemia
- Hyperinsulinemia
Treatment Options
Intensive Nutritional Support
SUPPORTIVERecombinant Human Insulin
MODERATELY EFFECTIVEIGF-1 Therapy (Mecasermin)
MODERATELY EFFECTIVE Approved 2005Diazoxide
MODERATELY EFFECTIVEGastrostomy Tube Feeding
SUPPORTIVEDiagnosis
- Clinical evaluation
- Genetic testing (INSR gene sequencing)
- Measurement of insulin and glucose levels
- Physical examination revealing characteristic features
- Insulin receptor binding studies
History
Donohue syndrome was first described by Dr. William L. Donohue in 1948, who reported a case of a patient with severe insulin resistance and unusual physical features. The genetic basis of the disease, involving mutations in the INSR gene, was later elucidated.
Recent Breakthroughs
Long-term treatment with recombinant methionyl human IGF-1 (rhIGF-1) improves growth and metabolic control in patients with genetically defined Donohue syndrome
A study published in the Journal of Clinical Endocrinology & Metabolism showed that long-term treatment with rhIGF-1 can improve growth and metabolic control in patients with Donohue syndrome. This suggests that rhIGF-1 may be a useful therapy for improving the outcomes of patients with this condition.