Donohue syndrome

Donohue syndrome (also known as Leprechaunism) is an extremely rare congenital disorder associated with impaired insulin metabolism. Severe forms of the disease are highly dangerous and usually result in miscarriage of the affected fetus or relatively early death after birth. Milder forms allow for somewhat longer survival.

Causes

The cause is a genetic mutation leading to various hormonal abnormalities, most notably a defect of the insulin receptors. These receptors are structures on the surface of body cells that bind insulin and allow glucose to enter the cells. Disruption of the hormonal system results in complex and severe clinical features.

Symptoms

In affected individuals, adipose tissue is virtually absent, giving them an unusual, aged appearance already at birth. Growth is slow, lips are thickened, nostrils are widened, and the ears are protruding. Enlarged external genitalia are often present. The appearance of affected individuals is traditionally compared to the mythical Irish leprechaun, hence the alternative name Leprechaunism.

Due to ineffective insulin receptor function, affected individuals develop insulin resistance typical of type 2 diabetes mellitus—insulin levels are elevated (hyperinsulinemia), but glucose uptake by cells is impaired. In addition, affected individuals commonly exhibit low blood glucose levels (hypoglycemia), the mechanism of which is not fully understood (insulin resistance is typically associated with hyperglycemia). This is most likely a consequence of a complex disturbance of carbohydrate metabolism in individuals with the syndrome.

Diagnosis

Based on clinical features, suspicion of the disorder may be raised; however, definitive confirmation requires genetic testing.

Treatment

The disease is congenital, and therefore prevention is not possible. Experimental attempts have been made using administration of a modified compound known as IGF (insulin‑like growth factor), which reportedly has a relatively favorable therapeutic effect.

• starecký vzhľad po narodení (nevyvíja sa tukové tkanivo)
• pomalý rast
• zväčšené vonkajšie pohlavné orgány
• rozšírené nosné dierky
• inzulínovaá rezistencia
• znížená koncetrácia cukru v krvi (komplexná porucha metabolizmu cukrov)