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.