Leprechaunism (Donohue syndrome) is the most severe type of insulin receptor 
(INSR) gene anomaly with the majority of patients surviving for only 2 years. We 
report a surviving 2 -year-old male with leprechaunism, bearing novel compound 
heterozygous mutations in the INSR. The patient is a Japanese boy with 
acanthosis nigricans, lack of subcutaneous fat, hirsutism, thick lips, gum 
hypertrophy and extremely high insulin levels (6702 mU/mL). He was as having 
identified novel compound heterozygous mutations in INSR (p.T910M and p. 
E1047K). At 24 day-old, recombinant human insulin-like growth factor 1 (rh-IGF1) 
treatment was started because of poor weight gain. At 2 years old, the patient's 
serum glucose level and HbA1C value had worsened, and both a bolus of rh-IGF-1 
and a subcutaneous injection of a rapid-acting insulin analog after meals, in 
addition to α-glycosidase inhibitor, were initiated from 2 years onward. Oxygen 
administration and biphasic positive airway pressure treatment were also 
initiated from 2 years old due to upper airway obstruction with adenoidal 
hypertrophy. In the experiments conducted using COS7 cells homozygously 
transfected with the INSR mutation, T910M INSR failed to process the proreceptor 
and decreased insulin-stimulated tyrosine phosphorylation. E1047K INSR resulted 
in a complete absence of insulin-stimulated tyrosine phosphorylation. These 
findings suggest the near absence of INSR in this patient. We consider that the 
rhIGF1 treatment contributed to his long survival, but it was not able to 
prevent his diabetic condition. Our report provides important insights into the 
function of INSR, and for the treatment of leprechaunism.