ESPE Abstracts

Introduction: Leprechaunism syndrome is a very rare genetic autosomal recessive disorder (Prevalence 1 in a million births), and is caused by mutations in the insulin receptor gene.

Case presentation: We report the case of a 5-month-old Algerian female, born to consanguineous parents. Birth was via caesarean section at 37 weeks gestation due to severe intrauterine growth restriction: birth weight 1800 g (< - 3.66SD), head circumference 32 cm (< - 2.6SD), length 42 cm (< - 5.37 SD). Apgar scores were 9/10 and 10/10. The child was admitted to our department at the age of 4 months in a critical condition, presenting with tachycardia, high fever (39.7°C), cholestatic jaundice, and distended abdomen. Clinical examination showed a septic child with emaciation, weight : 2200 kg (-7.7), length : 45 cm (-7.6 lipoatrophy, clitoromegaly, skin abnormalities, abdominal distension, hypertrichosis, and dysmorphic features including craniofacial abnormality with elfin facies and large, low-set ears. Neurological examination was normal. Laboratory results revealed hyperinsulinism, 560.4 pmol/l (14 – 140), fasting hypoglycaemia (24 mg/dL) and postprandial hyperglycaemia (170 mg/dL), hypocholesterolemia (50 mg/dL), hypotriglyceridemia (36 mg/dL), cholestatic jaundice (direct bilirubin : 4.6 mg/dL; indirect bilirubin : 6.5 mg/dL), C-Peptide : 947 pmol/l (reference range 95.4 - 455.8). C-reactive protein level: 65 mg/l Based on the typical dysmorphic characteristics and laboratory findings especially the exaggerated hyperinsulinemia, a clinical diagnosis of Donohue syndrome (Leprechaunism) was made. This was confirmed by DNA analysis which showed a homozygous deletion in 19 p13.2 encompassing exon 2 of the insulin receptor gene (INSR). Immediate antibiotic treatment was administered and growth hormone therapy was started because of poor weight gain in the dose of 0.35 mg/k/dy. However, three days later, the patient’s condition deteriorated dramatically with bradycardia, leading to cardiac arrest and death from apparent septicaemia (blood cultures positive on anaerobic culture).

Discussion: In this case we report Leprechaunism syndrome in an infant featuring typical phenotypic abnormalities, metabolic symptoms, severe pre- and postnatal growth retardation and multiple endocrine dysfunctions with insulin resistance. The typical phenotypic features and the metabolic syndrome in Leprechaunism disease might be explained by the reduction of sex hormone-binding globulin provoked by insulin action via the type 1 insulin-like growth factor (1 IGF) receptor, which has functional and structural similarities with the insulin receptor

Conclusion: This very rare genetic disease is challenging to treat clinically. Its prevalence in Arab countries is accounted for by the high incidence of consanguineous marriage.