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.
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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