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Review
. 2022 Feb 19;17(1):61.
doi: 10.1186/s13023-022-02214-y.

Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families

Indraneel Banerjee  1 , Julie Raskin  2 , Jean-Baptiste Arnoux  3 , Diva D De Leon  4 , Stuart A Weinzimer  5 , Mette Hammer  6 , David M Kendall  6 , Paul S Thornton  7
Affiliations
Review

Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families

Indraneel Banerjee et al. Orphanet J Rare Dis. .

Erratum in

Abstract

Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children, and carries a considerable risk of neurological damage and developmental delays if diagnosis and treatment are delayed. Despite rapid advances in diagnosis and management, long-term developmental outcomes have not significantly improved in the past years. CHI remains a disease that is associated with significant morbidity, and psychosocial and financial burden for affected families, especially concerning the need for constant blood glucose monitoring throughout patients' lives.

Results: In this review, we discuss the key clinical challenges and unmet needs, and present insights on patients' and families' perspective on their daily life with CHI. Prevention of neurocognitive impairment and successful management of patients with CHI largely depend on early diagnosis and effective treatment by a multidisciplinary team of specialists with experience in the disease.

Conclusions: To ensure the best outcomes for patients and their families, improvements in effective screening and treatment, and accelerated referral to specialized centers need to be implemented. There is a need to develop a wider range of centers of excellence and networks of specialized care to optimize the best outcomes both for patients and for clinicians. Awareness of the presentation and the risks of CHI has to be raised across all professions involved in the care of newborns and infants. For many patients, the limited treatment options currently available are insufficient to manage the disease effectively, and they are associated with a range of adverse events. New therapies would benefit all patients, even those that are relatively stable on current treatments, by reducing the need for constant blood glucose monitoring and facilitating a personalized approach to treatment.

Keywords: Caregiver burden; Challenges; Congenital hyperinsulinism; Hypoglycemia; Unmet needs.

Plain language summary

Congenital hyperinsulinism (CHI) is a rare disease that causes newborn babies and children to have low blood sugar because of the abnormal release of insulin. Insulin is a hormone produced by the pancreas that promotes the transfer of sugar from the blood into the body’s cells. In a healthy person, insulin is released only after a meal when the level of blood sugar is high, but infants and children with CHI make insulin even if the blood sugar is low. This can lead to dangerously low blood sugar levels, which can cause brain damage if left untreated. Unfortunately, diagnosis and treatment are often delayed, resulting in avoidable brain damage and developmental delays in these children. CHI is associated with substantial stress and anxiety for the families, especially due to the need for frequent feeding and the fear of low blood sugars added to the constant need to measure blood sugar levels. This article discusses the most important challenges and unmet needs in this rare disease, including the limited treatment options, the side effects of available treatment options and the heavy psychological, social and financial burden on affected families. Effective screening of newborns for CHI needs to be improved, and quick referral to specialized treatment centers is necessary to ensure the best outcomes for patients and families. In addition, awareness of CHI has to be raised in all medical professions caring for newborns and infants, and new medications are urgently needed to ensure the best possible treatment for all patients with CHI.

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Conflict of interest statement

IB has been involved (independently of this work) in research contracts with Crinetics Pharmaceuticals, Dexcom Incorporated, Merck Serono and Zealand Pharma. He has received fees for advisory board meetings with Merck Serono. He has national commitments as Chair of the British Society of Paediatric Endocrinology and Diabetes Clinical Study Group, Audit and Peer Review Officer of the BSPED, Chair of the European Society for Paediatric Endocrinology, and co-opted member of the Head Injury Guidelines Committee for the National Institute of Health and Care Excellence in the UK. JR is an employee of CHI International, who have received sponsorship for events from Amidebio, Betabionics, Crinetics Pharmaceuticals, Eiger, Hanmi, Rezolute, Twist and Zealand Pharma over the past 3 years. Crinetics Pharmaceuticals, Eiger, Hanmi Pharmaceuticals, Rezolute and Zealand Pharma are current sponsors of the HI Global Registry. JR does not receive any fees directly from the companies. J-BA received consulting fees (independent of this work) from Alexion, BioMarin, Immedica, Lucane Pharma and Zealand Pharma, and speaker fees from Pierre Fabre and Sanofi Genzyme. DDDL received consulting fees (independent of this work) from Crinetics Pharmaceuticals, Hanmi Pharmaceuticals, Heptares Therapeutics, Poxel Inc., Soleno Therapeutics and Zealand Pharma, and research support from Crinetics Pharmaceuticals, Tiburio Pharma, Twist Pharma and Zealand Pharma. DDDL owns stock options from Merck & Co through spouse employment. SAW received speaker fees (independent of this work) from Abbott, Dexcom and Medtronic, and serves as a consultant for Zealand Pharma A/S. MH and DMK are full-time employees and shareholders of Zealand Pharma A/S, Soborg, Denmark. PST received payments (independent of this work) from Ascendis, Novo Nordisk, Opko Biologics, Rezolute, Spruce, Xeris Pharmaceuticals and Zealand Pharma for performing research studies, and payments from Johnson and Johnson and Nutricia for expert testimony.

Figures

Fig. 1
Fig. 1
Data from the HI Global Registry global access survey, ‘Medication Management’ survey, ‘Glucose Monitoring’ survey, ‘Diet and Feeding Management’ Survey [45]. a Responses of 83 pediatric endocrinologists in 45 countries globally to questions about access to diazoxide in their country (Algeria, Argentina (2), Australia (2), Bangladesh, Belgium, Brazil (2), Bulgaria (3), Canada (5), Chile, China, Colombia (4), Egypt, Georgia, Germany (3), Ghana, Greece, Haiti, Hong Kong, Hungary, Iceland, India (9), Iraq (2), Israel, Japan, Kosovo, Lebanon, Luxembourg, Mexico (2), Montenegro, Myanmar, the Netherlands, Peru (6), Romania, Russia, Saudi Arabia, Serbia (2), Spain, Sudan, Sweden, Switzerland, Tanzania, United Kingdom (3), Ukraine (2), USA (4), Venezuela). b Reported frequency of hypoglycemia (plasma glucose < 4.0 mmol/L) and current medication use (n = 78). c Reported feeding frequency in 24 h and frequency of hypoglycemia (plasma glucose < 4.0 mmol/L) for individuals on CHI treatment (n = 75). HI, hyperinsulinism
Fig. 2
Fig. 2
Deidentified quotes of parents of children diagnosed with CHI (provided by CHI International). CHI, congenital hyperinsulinism
See this image and copyright information in PMC

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