Longitudinal Auxological recovery in a cohort of children with Hyperinsulinaemic Hypoglycaemia

Abstract

Background: Hypoglycaemia due to hyperinsulinism (HI) is the commonest cause of severe, recurrent hypoglycaemia in childhood. Cohort outcomes of HI remain to be described and whilst previous follow up studies have focused on neurodevelopmental outcomes, there is no information available on feeding and auxology. Aim: We aimed to describe HI outcomes for auxology, medications, feeding and neurodevelopmental in a cohort up to age 5 years. Method: We reviewed medical records for all patients with confirmed HI over a three-year period in a single centre to derive a longitudinal dataset. Results: Seventy patients were recruited to the study. Mean weight at birth was − 1.0 standard deviation scores (SDS) for age and sex, while mean height at 3 months was − 1.5 SDS. Both weight and height trended to the population median over the follow up period. Feeding difficulties were noted in 17% of patients at 3 months and this reduced to 3% by 5 years. At age 5 years, 11 patients (15%) had neurodevelopmental delay and of these only one was severe. Resolution of disease was predicted by lower maximum early diazoxide dose (p = 0.007) and being born SGA (p = 0.009). Conclusion: In a three-year cohort of HI patients followed up for 5 years, in spite of feeding difficulties and carbohydrate loading in early life, auxology parameters are normal in follow up. A lower than expected rate of neurodevelopmental delay could be attributed to prompt early treatment.

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

“…Prolonged hospitalizations until an effective treatment is identified can require parents to be away from home and work for long periods of time [ 14 ]. Most long-term follow-up studies have focused on neurodevelopmental outcomes and time to resolution, but there are few descriptions of the natural history of CHI with regard to growth, weight, feeding or medication use [ 61 ].…”

Long-Term Outcome and Treatment in Persistent and Transient Congenital Hyperinsulinism: A Finnish Population-Based Study

“…The proportion of the medically treated P-CHI patients who were able to discontinue medication (68%) fell between 61% ( 33 ) and 95% ( 34 ) reported by previous studies (both calculated from their data, excluding patients who we would have classified as having T-CHI) Although the study designs in these 3 cohorts were different, these findings indicate a high probability of spontaneous remission of drug-responsive CHI, occurring most often before school age, but sometimes even in adulthood. The similar recovery frequency in mutation-positive and mutation-negative groups in the current study likely reflects the relatively high number of dominant CHI variants.…”

Clustering of Hypoglycemia Events in Patients With Hyperinsulinism: Extension of the Digital Phenotype Through Retrospective Data Analysis

“…Patients with IKH do not have underlying metabolic disturbances and are therefore capable of mounting adequate counter-regulatory responses. In contrast, those positive for HI mutations tend to have more severe disease [ 11 ] and less ability to mount counter-regulatory responses. Further investigation of the metabolic and counter-regulatory hormonal milieu in patients with HI may be required to refine specific causation.…”

“…Significant progress in the understanding of the underlying pathophysiology of HI has been made since its first detailed description in 1953 [ 6 ]. Increased knowledge of changes at the organic [ 7 ], cellular [ 8 ], and genetic [ 9 , 10 ] levels has led to improvements in the care of these patients, and recent studies even suggest a lowering of the subsequent rate of brain injury [ 11 ]. As first suggested by Richard Dawkins in 1976, there is an “extended phenotype” of all conditions, not just limited to observable physical traits or cellular changes [ 12 ].…”