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NORD is very grateful to Dr. Ali Baykan, Erciyes University Department of Pediatric Cardiology, Kayseri, Turkey, for assistance in the preparation of this report.
Leprechaunism is an extremely rare disorder characterized by abnormal resistance to insulin that results in a variety of distinguishing characteristics, including growth delays and abnormalities affecting the endocrine system (i.e., the system of glands that secrete hormones into the blood system). Affected infants may also have distinctive characteristics of the head and face (craniofacial region), low birth weight, skin abnormalities, and enlargement of the breast and clitoris in females and the penis in males. Leprechaunism is inherited as an autosomal recessive genetic trait.
Leprechaunism is characterized by growth delays, as well as abnormalities of the head and face (craniofacial region) and of the endocrine system. Many of the symptoms associated with leprechaunism are present at birth (congenital). The range and severity of symptoms and physical characteristics may vary from case to case.
In most instances, infants with leprechaunism exhibit delayed growth before and after birth (pre- and postnatal growth deficiency), delayed bone age or maturation. Affected infants tend to have a low birth weight, may fail to gain weight or grow at the expected rate (failure to thrive), and may become abnormally thin (emaciated). They often lack muscle mass.
Infants with leprechaunism have distinctive facial features, including abnormally large, low-set and poorly developed ears; an unusually flat bridge of the nose; large, thick lips; an abnormally large mouth (macrostomia); and widely spaced eyes (hyptertelorism). Affected infants may also have an abnormally small head (microcephaly).
In most cases, leprechaunism is associated with abnormal darkening and thickening of patches of skin in certain areas of the body (acanthosis nigricans), unusual thickening of the skin (pachyderma), excessive hair growth (hirsutism), and malformation (dysplasia) of the nails. In addition, infants with leprechaunism exhibit absence of most of the body fat under the skin (subcutaneous adipose tissue).
Leprechaunism is also characterized by abnormalities of the endocrine system (i.e., the system of glands that secrete hormones into the blood system). Such abnormalities include excessive secretion of the hormone insulin (hyperinsulinemia). Insulin regulates blood sugar (glucose) levels by promoting the movement of glucose into bodily cells. Infants with leprechaunism fail to use insulin effectively (insulin resistant). Because of this, they may experience abnormally high blood sugar levels (hyperglycemia) after eating a meal (postprandial) and abnormally low blood sugar levels (hypoglycemia) when not eating.
Additional abnormalities resulting from improper function of the endocrine system include abnormal enlargement of the breast and clitoris in females and the penis in males. In some cases, cysts have formed in the ovaries. Hypertrophic cadiomyopathy may be seen in these patients as in diabetic mother babies.
Infants with leprechaunism may experience additional abnormalities, including intellectual disability, abnormally large hands and feet, an unusually widened (dilated) or enlarged (distended) stomach, abnormal amounts of iron in the liver, and/or stoppage of the flow of bile (cholestasis) from the liver. In addition, affected infants may experience protrusion of portions of the large intestine through an abnormal opening in musculature lining the abdominal cavity in the area of the groin (inguinal hernia) or protrusion of part of the intestine through the abdominal wall near the navel (umbilical hernia). Affected infants are also more susceptible to repeated infections.
Leprechaunism is inherited as an autosomal recessive genetic trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Investigators have determined that leprechaunism may be caused by disruption or changes (mutations) of the insulin receptor gene located on the short arm (p) of chromosome 19 (19p13.2). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q." Chromosomes are further subdivided into bands that are numbered. For example, "chromosome 19p13.2" refers to band 13.2 on the short arm of chromosome 19.
Due to the mutation in the insulin receptor gene, individuals with leprechaunism are unable to use insulin effectively. Insulin is a hormone produced by the pancreas that plays an important role in the absorption of sugar (glucose) into muscle cells. Glucose is the body's main source of energy. Some symptoms associated with leprechaunism, including growth deficiencies and hyperglycemia, develop as a result of severe insulin resistance of affected individuals.
In reported cases, leprechaunism has occurred twice as often in females as in males (F2:M1). More than 50 cases have been reported in the medical literature. Leprechaunism was first identified in the 1948 by Dr. W.L. Donohue.
Symptoms of the following disorders can be similar to those of leprechaunism. Comparisons may be useful for a differential diagnosis:
Patterson pseudoleprechaunism syndrome is an extremely rare genetic disorder characterized by a normal birth weight, bronze discoloration of the skin (hyperpigmentation), loose skin on the hands and feet (cutis gyrata), and malformation (dysplasia) of the skeleton. Abnormalities affecting the endocrine system include enlargement of the adrenal glands and the adrenal cortex (hyperadrenocorticism) and diabetes mellitus. The exact cause of Patterson pseudoleprechaunism syndrome is not known.
Williams syndrome is a rare genetic disorder characterized by growth delays before and after birth (prenatal and postnatal growth retardation), short stature, varying levels of mental deficiency, and distinctive facial abnormalities that typically become more pronounced with age. Characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually held open, and a broad nasal bridge with nostrils that flare forward (anteverted nares). Affected individuals may also have unusually short eyelid folds (palpebral fissures), flared eyebrows, a small lower jaw (mandible), and prominent ears. Dental abnormalities may also be present including abnormally small, underdeveloped teeth (hypodontia) with small, slender roots. Williams syndrome is associated with peripheral pulmonary stenosis and supravalvular aortic stenosis. Stenosis in arterial system may be seen on renal arteries, too. Williams syndrome may also be associated with heart (cardiac) defects, abnormally musculoskeletal defects, and/or other abnormalities. In addition, most affected individuals have mild to moderate intellectual disability; poor visual-motor integration skills; a friendly, outgoing, talkative manner of speech; and a short attention span with easy distractibility. In most individuals with Williams syndrome, the disorder appears to occur spontaneously for unknown reasons (sporadically). (For more information on this disorder, choose "Williams syndrome" as your search term in the Rare Disease Database.)
The diagnosis of leprechaunism may be confirmed by a thorough clinical evaluation, a detailed patient history, identification of characteristic symptoms and physical findings. The diagnosis requires measurement of insulin levels, with a blood test, and confirmation of defective insulin binding on the cells known as fibroblasts.
Prenatal diagnosis is possible through analysis of DNA obtain through a procedure known as amniocentesis. During amniocentesis, a sample of fluid that surrounds the developing fetus (amniotic fluid) is removed and studied. DNA obtained from amniotic cells is analyzed through a test known as polymerase chain reaction (PCR). PCR, a laboratory technique that many have described as a form of "photocopying," enables researchers to enlarge and repeatedly copy sequences of DNA. As a result, they are able to closely analyze DNA and more easily identify genes and genetic changes (mutations). In leprechaunism, polymerase chain reaction is used to identify mutations to the insulin receptor gene.
The treatment of leprechaunism is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who assess and treat endocrine abnormalities (endocrinologists), and specialists who assess and treat skin abnormalities (dermatologists) and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co; 1997:599.
Magalini SI, et al, eds. Dictionary of Medical Syndromes. 4th ed.New York, NY: Lippincott-Raven Publishers; 1997:233.
Gorlin RJ, et al, eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:822.
Buyce ML, ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:1044-45.
Baykan A, et al. Hypertrophic cardiomyopathy with leprechaunism. J Pediatr Endocrinol Metab. 2008;21(4):317-8.
Nakae J, et al. Long-term effect of recombinant human insulin-like growth factor I on metabolic growth control in a patient with leprechaunism. J Clin Endocrinol Metab. 1998;83:542-9.
Kosztolanyi G. Leprechaunism/Donohue syndrome/insulin gene mutations: a syndrome delineation story from clinicopathological description to molecular understanding. Eur J Pediatr. 1997;156:253-5.
Gurgey A, et al. Leprechaunism is two Turkish patients. Turk J Pediatr. 1997;39:387-93.
Longo N, et al. Prenatal diagnosis of the insulin receptor gene in a family with leprechaunism. Prenat Diagn. 1995;15:1070-4.
Longo N, et al. Two mutations in the insulin receptor gene of a patient with leprechaunism: application to prenatal diagnosis. J Clin Endocrinol Metab. 1995;80:1496-501.
Imamura T, et al. Donohue's syndrome. Nippon Rinsho. 1994;52:2643-7.
Ioan D, et al. Leprechaunism: report of two cases and review. Endocrinologie. 1988;26:205-9.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Donohue Syndrome. Entry No: 246200. Last Edited February 14, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed September 19, 2012.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Williams-Beuren Syndrome; WBS. Entry No: 194050. Last Edited August 17, 2012. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed September 19, 2012.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Patterson Pseudoleprechaunism Syndrome. Entry No: 169170. Last Edited September 9, 2010. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed September 19, 2012.
Report last updated: 2012/09/19 00:00:00 GMT+0