Read more about this disease, some with Classification – Types – Signs and symptoms – Genetics – Pathophysiology – Diagnosis – Screening – Prevention – Treatment and management – Cures and much more, some including pictures and video when available.
Donohue syndrome (also known as Leprechaunism) is an extremely rare and severe genetic disorder. Leprechaunism derives its name from the fact that those afflicted with the disease often have elfin features and are smaller than usual. Affected individuals have an insulin receptor with greatly impaired functionality.
Facial features indicative of Donohue syndrome include protuberant and low-set ears, flaring nostrils, and thick lips. Physical features include stunted growth (including during gestation), an enlarged clitoris and breasts in affected females, and an enlarged penis in affected males. In the Journal of Pediatric Medicine, Donohue and Uchida described affected sisters whose growth appeared to have ended in the seventh month of gestation, both born alive but dying before four months of age.[1] Very early death (or spontaneous abortion) is the norm, although sufferers sometimes live longer than a decade.[1][2]
As the mutation causing the disorder affects insulin receptor function, those with the disease are also insulin resistant, with hypoglycemia and profound hyperinsulinemia (very high levels of insulin in the blood)[1] Another feature of the disease is that the subcutaneous Adipose tissue is markedly diminished. (Contributing to the unusual appearance of affected individuals.)
A much milder form of the disease, in which there is some insulin resistance but normal growth and subcutaneous fat distribution, is also known.[3] It is caused by a less severe mutation of the same gene.
Donohue syndrome is an autosomal recessive genetic disorder. The mutations responsible for the disorder are found on the short arm chromosome 19 (19p13.2) within the coding sequence of the INSR gene (insulin receptor) causing the production of inactive receptor molecules.[2] There are several mutations that can be responsible for the disease, as any mutation that severely impairs the functionality of the insulin receptor will have similar effects. The INSR gene spans over one hundred and twenty thousand base pairs, which contain twenty-two exons coding for a protein that consists of 1382 amino acids. [4]. Some of the introns may or may not be spliced out depending on the kind of cell. [5]
Known mutations to the gene which can cause Donahue syndrome include a nonsense mutation that resulted in a frame shift[6], a single missense mutation[1] and in the milder form mentioned above, a single codon change that altered isoleucine to methionine in the receptor protein.[1] Some mutations to the gene instead result in insulin resistant diabetes without Donahue syndrom.[1]
As the mutations are extremely rare, most cases are the result of consanguineous matings, for instance between cousins.[1]. However, the exact mutation need not be the same: a sufferer may have two different mutant alleles.[7]
A heterozygous individual (i.e. one who is a carrier for the disease, having only one normal allele for the insulin receptor) will not be affected. Two heterozygous parents have, in theory, a one in four chance of having a child with the disease, and two thirds of their unaffected children will be carriers. However, because spontaneous abortion (miscarriage) often results when the fetus has the disease, in actuality the proportion of children born alive with Donahue syndrome will be lower than 25%.[1]
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