Mecasermin in Insulin Receptor-Related Severe Insulin Resistance Syndromes: Case Report and Review of the Literature

Abstract

Mutations in the insulin receptor (INSR) gene underlie rare severe INSR-related insulin resistance syndromes (SIR), including insulin resistance type A, Rabson–Mendenhall syndrome and Donohue syndrome (DS), with DS representing the most severe form of insulin resistance. Treatment of these cases is challenging, with the majority of DS patients dying within the first two years of life. rhIGF-I (mecasermin) has been reported to improve metabolic control and increase lifespan in DS patients. A case report and literature review were completed. We present a case involving a male patient with DS, harbouring a homozygous mutation in the INSR gene (c.591delC). Initial rhIGF-I application via BID (twice daily) injection was unsatisfactory, but continuous subcutaneous rhIGF-I infusion via an insulin pump improved weight development and diabetes control (HbA1c decreased from 10 to 7.6%). However, our patient died at 22 months of age during the course of a respiratory infection in in Libya. Currently available data in the literature comprising more than 30 treated patients worldwide seem to support a trial of rhIGF-I in SIR. rhIGF-I represents a treatment option for challenging SIR cases, but careful consideration of the therapeutic benefits and the burden of the disease is warranted. Continuous application via pump might be advantageous compared to single injections.

Severe insulin resistance syndrome – A rare case report and review of literature

“…The alteration in phenotype leads to overproduction of pro-inflammatory cytokines which are then responsible for severe gingival inflammation that contributes to the reduction of quality as well as quantity of bone around the erupting tooth and shortens the eruption distance through the bone. [ 10 11 12 13 14 ]…”

Intrauterine Growth Restriction and Hypertrophic Cardiomyopathy as Prenatal Ultrasound Findings in a Case of Leprechaunism

“…rhIGF-I has been postulated as a potential therapeutic option in DS by stimulating peripheral glucose use and suppressing hepatic glucose production in order to reduce hyperinsulinemia and pseudoacromegalic characteristics [McDonald et al, 2007;Plamper et al, 2018]. The long-term aim is to improve glycemia, promote linear growth, and prolong survival [McDonald et al, 2007].…”

“…The long-term aim is to improve glycemia, promote linear growth, and prolong survival [McDonald et al, 2007]. There is no standard protocol, and only 6 case reports, reviewed by Plamper et al [2018], describe successful long-term use of rhIGF-I in patients with leprechaunism. Early treatment and continuous administration of rhIGF-I seem to be more beneficial [Nakae et al, 1998;Weber et al, 2014].…”

“…Early treatment and continuous administration of rhIGF-I seem to be more beneficial [Nakae et al, 1998;Weber et al, 2014]. Used doses range from 80 to 1,120 μg/kg/day [Plamper et al, 2018]. In most treated children, levels of blood glucose, insulin, and glycosylated hemoglobin decreased, growth parameters improved, sometimes HCM also improved, and survival was prolonged [Nakae et al, 1998;McDonald et al, 2007;Plamper et al, 2018;Ben Harouch et al, 2019].…”

Correct nomenclature is important, as highlighted by inappropriate interchangeability of “leprechaunism” with Donohue syndrome

“…5,7 Patients having DS present with a broad variety of physical abnormalities and metabolic symptoms, summarized in Table 1. [7][8][9] Most children having classic DS die within the first 2-years of life as a result of intercurrent infections of the upper airways, hypoglycaemia, or cardiomyopathy. 10 In summary, the term "leprechaun" connotes a stereotypical imaginary caricature accompanied with a degree of mirth, as opposed to DS which unfortunately is a serious and fatal condition.…”