Donohue Syndrome

Rare inherited condition caused by resistance to insulin with growth deficiency and characterized by dysmorphic facies (“elfin-like”), severe growth retardation, hirsutism, and multiple endocrine disorders.

Leprechaunism.

Endocrine disorder characterized by resistance to insulin caused by abnormal insulin receptors. First described by W.L. Donohue and I.A. Uchida in 1954.

Approximately 50 cases have been reported in the literature, but the incidence is estimated to be approximately 1:4,000,000 live births.

Autosomal recessive. The defective gene, which is responsible for encoding of the insulin receptor, has been mapped to 19p13.2. Parental consanguinity is likely for this disorder.

The primary defect in leprechaunism is located in the insulin receptor, but a secondary associated defect probably is responsible for growth failure because of an impaired response to endogenous growth hormone. This finding may be explained by the fact that the cytoplasmic subunit of the insulin receptor shares similarities with other receptors that have tyrosine kinase activity (e.g., insulin-like growth factor-1, epidermal and platelet-derived growth factor, and certain protooncogenes).

Clinical aspect and measurement of blood glucose and insulin levels. Prenatal diagnosis is available.

The synonym for this syndrome, leprechaunism, is derived from “leprechaun,” the name of a mythical little hairy elf originating from the Irish folklore. Patients have an elfin or gnome-like face with microcephaly, protuberant and low-set ears, large, wide-set eyes, high arched palate, thickened lips, and severely diminished subcutaneous fat (general lipodystrophy) and muscle mass. Skin abnormalities include hypertrichosis (also reflected in the name leprechaun), acanthosis nigricans, and pachyderma. Insulin resistance characterizes the metabolic abnormalities, such as severe hyperinsulinemia, postprandial hyperglycemia, and paradoxical fasting hypoglycemia. Intrauterine and postnatal growth retardation seem to result from a diminished response to growth hormone, at least partially because of downregulation of growth hormone receptors by high insulin levels. The genitalia are enlarged, and cystic changes in the gonads occur frequently in girls. The abdomen often is distended, and the presence of umbilical and/or inguinal hernias is not uncommon. Some patients have cardiac involvement, such as atrial septal defect or, more commonly, myocardial hypertrophy, which may be severe. Although some patients survived for several years, most die of severe failure to thrive with recurrent infections in the first year of life. Rare cases of survival beyond infancy have been attributed to the presence of residual insulin receptor function.

Obtain a blood sugar level prior to going to the operating room. If cardiac disease is suspected, obtain an ECG and an echocardiogram.

General and regional anesthesia, in the same newborn, for two different surgeries have been reported with no major complications related to the type of anesthesia. Except for very short surgeries, regular blood glucose measurements should be performed and a dextrose-containing intravenous solution administered to detect and prevent hypoglycemia, respectively. In the presence of hypertrophic cardiomyopathy, tachycardia, hypotension, hypovolemia, and an increase in contractility must be avoided.

Depending on the congenital cardiac defect and the type of procedure, subacute bacterial endocarditis prophylaxis may be necessary.

Other progeroid syndromes including the following:

Progeria Syndrome: Premature aging with increased urinary excretion of hyaluronic acid caused by a sporadic dominant mutation.

Berardinelli-Seip Syndrome: Inherited disorder with hyperinsulinemia as a consequence of insulin resistance combined with lipodystrophy and acromegaloid features (enlarged external genitalia, increased skeletal growth with acromegaloid appearance, diabetes mellitus with generalized loss of body fat, hepatomegaly, and acanthosis nigricans).

De Barsy Moens Diercks Syndrome: Autosomal recessive disorder featuring cutis laxa, frontal bossing and prominent ears, athetosis, cloudy cornea, hypotonia and hyperlaxity of joints, and/or short stature.

Cockayne Syndrome: DNA repair syndrome characterized by short stature, premature aging, and photophobia, which is aggravated by UV exposure but has no link to cancer development.

Hallerman-Streiff Syndrome: Sporadic malformation syndrome characterized by short stature, microphthalmia, brittle teeth, growth retardation, upper respiratory tract obstruction, and scoliosis.

Congenital Disorders of Glycosylation: Group of multisystemic disorders characterized by dysmorphism, coagulation disorders, and psychomotor retardation. Multiple subtypes exist, of which type Ia is by far the most common.

Rabson-Mendenhall Syndrome: Genetic disorder with pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities.

Alström Syndrome: Inherited syndrome with progressive visual and hearing loss, diabetes mellitus, and cardiac, hepatic, and renal involvement.