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Hüseyin Özbey, MD; Nese Özbey, MD; Walter W. Tunnessen, Jr, MD
From the Departments of Pediatric Surgery (Dr H. Özbey) and Endocrinology, Nutrition and Metabolism (Dr N. Özbey), University of Istanbul, Istanbul Medical Faculty, Istanbul, Turkey; and the American Board of Pediatrics, Chapel Hill, NC (Dr Tunnessen).

Arch Pediatr Adolesc Med. 1998;152:1031-1032.

THIS 5-MONTH-OLD infant, the product of a consanguineous marriage, now weighs 3500 g. He has a lifelong history of poor growth with high blood glucose levels unresponsive to insulin. Recurrent rectal prolapse has resulted in chronic mechanical intestinal obstruction (Figure 1).

Figure.

Denouement and Discussion: Leprechaunism

Figure 1, left, The infant shows the typical "elfinlike" facies of leprechaunism with hirsutism, large, low-set ears, broad nasal tip and flared nares, and thick lips. Figure 1, right, Other prominent features present in this infant include reduced subcutaneous fat, prominent nipples, a distended abdomen, large external genitalia, and rectal prolapse.

CLINICAL FEATURES
Donohue¹ and Donohue and Uchida² were the first to describe this rare syndrome featuring dysmorphic facies, failure to thrive, hirsutism, and multiple endocrine abnormalities.² Leprechaunism was the euphemistic name used to describe the "elfinlike" facies and poor growth characteristic of the syndrome. The dysmorphic facial features include large, low-set ears, depressed nasal bridge with a broad nasal tip and flared nares, thick lips, and hirsutism. The body habitus is striking with a marked lack of subcutaneous fat, generalized hirsutism, acanthosis nigricans, prominent nipples, enlarged genitalia, abdominal distention, and loose skin.^3-4

ETIOLOGY AND GENETICS
The diagnosis of leprechaunism is usually made on the basis of the clinical appearance and laboratory evidence of hyperglycemia and extreme insulin resistance. Advances in molecular genetics have allowed the molecular basis of the syndrome to be delineated. The first insulin receptor gene mutation found in human disease was detected in an infant with leprechaunism.⁵ Insulin receptors are important for intrauterine growth, especially of muscle and fat. Mutation of the insulin receptor gene results in impaired insulin binding and altered receptor signaling resulting in intrauterine and postnatal growth restriction.^6-8

Excessive concentrations of epidermal growth factor found in affected infants are considered to be a factor that gives rise to hypertrophy of the skin, hypertrichosis, and prominence of the nipples.⁸ Other phenotypic and metabolic abnormalities may be the result of the combination of the lack of insulin receptor action and the overactivation of insulin-like growth factor 1 by insulin.^9-10

Leprechaunism is inherited in an autosomal recessive fashion. Prenatal diagnosis is possible by DNA analysis of chorionic villus biopsy specimens for mutations in the insulin receptor gene.⁷

PROGNOSIS
Infants with this rare syndrome usually die in infancy as a result of malnutrition and recurrent infections. Survival beyond early infancy has been attributed to the presence of residual insulin receptor function and the ability of pathologically elevated concentrations of insulin to transmit some signals through the homologous receptor for insulin-like growth factor 1.¹¹ All infants are profoundly motor and mentally retarded.

AUTHOR INFORMATION
Accepted for publication May 4, 1998.

Reprints: Hüseyin Özbey, MD, Department of Pediatric Surgery, University of Istanbul, Istanbul Medical Faculty, 34390, Capa-Istanbul, Turkey.

REFERENCES
1. Donohue WL. Dysendocrinism. J Pediatr. 1948;32:739-748. PUBMED 2. Donohue WL, Uchida I. Leprechaunism: a euphemism for a rare familial disorder. J Pediatr. 1954;45:505-519. 3. Longo N, Langley SD, Griffin LD, Elsas LJ. Reduced mRNA and a nonsense mutation in the insulin-receptor gene produce heritable severe insulin resistance. Am J Hum Genet. 1992;50:998-1007. ISI | PUBMED 4. Tokatli A, Özsoylu S, Özme S. Leprechaunism (Donohue's syndrome): a case report. Turk J Pediatr. 1993;35:319-322. ISI | PUBMED 5. Kadowaki T, Bevins CL, Cama A. Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance. Science. 1988;240:787-790. FREE FULL TEXT 6. Desbois-Mouthon C, Sert-Langeron C, Magre J. Deletion of Asn281 in the alpha-subunit of the human insulin receptor causes constitutive activation of the receptor and insulin desensitization. J Clin Endocrinol Metab. 1996;81:719-727. ABSTRACT 7. Longo N, Langley SD, Still MJ, Elsas LJ. Prenatal analysis of the insulin receptor gene in a family with leprechaunism. Prenatal Diagn. 1995;15:1070-1074. ISI | PUBMED 8. Hart LM, Lindout D, Van der Zon GCM. An insulin receptor mutant (Asp 707 Ala), involved in leprechaunism, is processed and transported to the cell surface but unable to bind insulin. J Biol Chem. 1996;271:18719-18724. FREE FULL TEXT 9. Frindik JP, Kemp SF, Fiser RH, Schedewie H, Elders MJ. Phenotypic expression in Donohue syndrome (leprechaunism): a role for epidermal growth factor. J Pediatr. 1985;107:428-430. FULL TEXT | ISI | PUBMED 10. Jospe N, Kaplowitz PB, Furlanetto RW. Homozygous nonsense mutation in the insulin receptor gene of a patient with severe congenital insulin resistance: leprechaunism and the role fo the insulin-like growth factor receptor. Clin Endocrinol (Oxf). 1996;45:229-235. FULL TEXT | PUBMED 11. Taylor SI, Cama A, Accili D. Mutations in the insulin receptor. Endocrinol Rev. 1992;13:566-595. FREE FULL TEXT

SECTION EDITOR: WALTER W. TUNNESSEN, JR, MD

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