Successful rhIGF1 treatment for over 5 years in a patient with severe insulin resistance due to homozygous insulin receptor mutation.
BACKGROUND
Congenital insulin resistance syndromes are caused by biallelic mutations within the insulin receptor gene (INSR). Recombinant human insulin-like growth factor (rhIGF1) has been used with mixed success; however, rigorous assessment of its efficacy is lacking. Here, we describe a child with a homozygous mutation in INSR successfully treated with rhIGF1 for more than 5 years.


METHODS
The patient presented with osmotic diabetes symptoms and was noted to have dysplastic dentition, hypertrichosis, coarse and dysmorphic facial features. Acanthosis nigricans, skin tags and rugated hyperkeratosis were also evident on the posterior neck, axilla and groin. A homozygous INSR essential splice site mutation (c.1268 + 2T > C, p.G374 fs*12) was identified, for which both parents were found to be heterozygous. The patient was treated with twice daily injections of rhIGF1 and metformin for more than 5 years with improvement in her acanthosis nigricans, hyperkeratosis and hypertrichosis. A dramatic fall in fasting insulin, HOMA-IR and HbA1c has been maintained over the entire course of treatment without adverse effects. Her linear growth velocity has remained on target for her predicted adult height.


CONCLUSIONS
Our case demonstrates the effectiveness of rhIGF1 as an early treatment in a patient with a biallelic mutation within INSR without evidence of fluid retention, retinopathy, muscle pain, heart failure, cerebral infarcts or benign intracranial hypertension. Her case suggests rhIGF1 can and should be considered as an initial treatment option instead of as a final option in those with INSR mutations.
Departments of Medicine and Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism, The University of Chicago, Chicago, IL, USA.
D
D
Carmody
Departments of Medicine and Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism, The University of Chicago, Chicago, IL, USA.
S S
SS
Ladsaria
Departments of Medicine and Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism, The University of Chicago, Chicago, IL, USA.
R K
RK
Buikema
University of Cambridge Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
R K
RK
Semple
Departments of Medicine and Pediatrics, Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism, The University of Chicago, Chicago, IL, USA.
S A W
SA
Greeley
D000052:Acanthosis Nigricans / Q000150:complications / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D006720:Homozygote; D020249:Hormone Replacement Therapy; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D009154:Mutation; D011972:Receptor, Insulin / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome
D015703:Antigens, CD; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; C435941:INSR protein, human; D011972:Receptor, Insulin