Overview
Leprechaunism, also known as Donohue syndrome, is an autosomal recessive disorder characterized by severe insulin resistance, hyperglycemia, hyperinsulinemia, distinctive dysmorphic features, and early mortality 167.Diagnosis
Clinical Features: Marked hyperinsulinemia, hyperglycemia, hypoglycemia postprandially, severe insulin resistance, dysmorphic features, failure to thrive, and early death 167.
Laboratory Tests: Elevated fasting insulin levels (often >2000 μU/mL), low fasting glucose (<20 mg/dL), and minimal glucose response to exogenous insulin administration 6.
Genetic Testing: Identification of mutations in the insulin receptor gene, often homozygous nonsense mutations 3.
Imaging and Pathology: Postmortem findings may include ovarian enlargement, islet cell hyperplasia, cholestasis, and hepatic bile duct paucity 1.Management
Insulin Sensitizers: Recombinant insulin-like growth factor I (IGF-I) has been attempted but showed no significant glucose-lowering or anabolic effects despite achieving supraphysiologic levels 2.
Supportive Care: Focus on nutritional support and management of complications such as hypoglycemia and hyperglycemia 6.
Monitoring: Regular assessment of metabolic parameters including glucose, insulin, and electrolytes 26.Special Populations
Pediatrics: Infants with leprechaunism often have severe growth failure despite adequate caloric intake 8.
Comorbidities: Presence of cystic ovarian enlargement and myocardial hypertrophy may indicate residual insulin action in specific tissues 5.Key Recommendations
Genetic Testing for Insulin Receptor Mutations: Essential for confirming the diagnosis and understanding the molecular basis of severe insulin resistance (Evidence: Strong 3).
Close Metabolic Monitoring: Regular evaluation of glucose, insulin levels, and electrolyte balance to manage acute complications (Evidence: Moderate 6).
Consider IGF-I Therapy with Caution: Despite lack of proven efficacy, recombinant IGF-I may be explored in severe cases, though its effectiveness remains unproven (Evidence: Weak 2).References
1 Gürgey A, Göğüş S, Saatçi U, Bilginturan N, Yordam N, Coşkun T et al.. Leprechaunism in two Turkish patients. The Turkish journal of pediatrics 1997. link
2 Backeljauw PF, Alves C, Eidson M, Cleveland W, Underwood LE, Davenport ML. Effect of intravenous insulin-like growth factor I in two patients with leprechaunism. Pediatric research 1994. link
3 Krook A, Brueton L, O'Rahilly S. Homozygous nonsense mutation in the insulin receptor gene in infant with leprechaunism. Lancet (London, England) 1993. link91820-c)
4 Elsas LJ, Longo N. Impaired insulin binding and excess glucose transport in fibroblasts from a patient with leprechaunism. Enzyme 1987. link
5 Geffner ME, Kaplan SA, Bersch N, Lippe BM, Smith WG, Nagel RA et al.. Leprechaunism: in vitro insulin action despite genetic insulin resistance. Pediatric research 1987. link
6 Elders MJ, Schedewie HK, Olefsky J, Givens B, Char F, Bier DM et al.. Endocrine-metabolic relationships in patients with leprechaunism. Journal of the National Medical Association 1982. link
7 Rigg BM. Leprechaunism. Annals of plastic surgery 1979. link
8 Adams JM, Gordon LP, Dutton RV, Rosenberg HS, Rudolph AJ. Leprechaunism (Donohue's syndrome) in a low birth weight infant. Southern medical journal 1977. link
9 Tsujino G. A case of leprechaunism and an analysis of some clinical manifestations of this syndrome. Zeitschrift fur Kinderheilkunde 1975. link