ESPE Abstracts (2015) 84 P-1-100

ESPE2015 Poster Presentations Poster Category 1 Perinatal (11 abstracts)

Atypical Features in Patients with Leprechaunism Suggesting a Wide Clinical Spectrum of Disease

Harshini Katugampola a , Nicola Improda a , Pratik Shah a, , Hannah Gordon a , Rakesh Amin a, , Catherine J Peters a, , Robert K Semple c & Mehul T Dattani a,

aLondon Centre for Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Trust, London, UK; bInstitute of Child Health, London, UK; cDepartment of Clinical Biochemistry, Institute of Metabolic Science, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK

Background: Donohue syndrome (DS) is the most severe form of insulin-resistance due to autosomal recessive mutations in the insulin receptor gene. Typical features include pre-/postnatal growth impairment, hyperinsulinaemic hyperglycaemia with fasting hypoglycaemia, nephrocalcinosis, recurrent sepsis, little adipose tissue, soft tissue overgrowth, hirsutism, acanthosis nigricans and facial dysmorphism. However, additional comorbidities may be present, affecting prognosis.

Case series: We describe four males with DS, treated with bolus rhIGF-1. Patients 1 and 3 were treated for three months, but manifested severe comorbidities (liver and respiratory failure) and sudden death. Patient 1 received a 3-year rhIGF-1 trial until age 5 years, and was referred at age 11.5 years with diabetes mellitus and recurrent ketoacidosis. Patient 2 received rhIGF-1/IGFBP3 until age 8 years and was then started on rhIGF-1. Table 1 summarizes the clinical picture of our cohort.

Table 1 (for abstract P1.100)
MutationHomozygous p.R1092QPaternal c.576C>G, p.l119M and maternal c.334C>T, p.R1039XHomozygous p.G84QHomozygous c.1924T>C, p.W642R
Age rhIGF-1 start (years)13.3 (second course)
RhIGF-1 duration (years)0.3100.30.5
Age (years)/cause of death14.7/unknown (recurrent sepsis and ketoacidosis)1.3/liver dysfunction: respiratory infection
ThyroidSecondary hypothyroidismSecondary hypothyroidism
SkinDiffuse psoriatic skin rashesHyperkeratosisHyperkeratosis
LiverProgressive cirrhosisMild cholestasis/hypoalbuminaemia
Clotting abnormalitiesLow factor IXProlonged coagulation, deficits in factors II, IX, XI, fibrinogen, ATIII, Prot CProlonged coagulation, deficits in factors II, IX, XI, fibrinogen
EyesBilateral cataract probably secondary to hyperglycaemiaDivergent squint astigmatic myopia
HeartMild bi-ventricular hypertrophyBiventricular hypertrophyMild pulmonary valvar stenosis, patent foramen ovale and ductus arteriosus, left ventricular hypertrophy
GutProtein losing inflammatory enteropathy
Electrolyte disturbanciesHypokalaemiaHypokalaemia and hyponatreamia

Conclusion: We report for the first time the presence of clotting abnormalities, diffuse psoriatic skin rashes and protein-losing inflammatory enteropathy in patients with DS. The relationship between additional comorbidities and genotype needs to be defined.

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