Hyperglycaemia-related complications at the time of diagnosis can cause permanent neurological disability in children with neonatal diabetes

J O Day,A W Patrick,K A Patel,A J Zeman,A T Hattersley,S E Flanagan,L Torrens,N Abid,M H Shepherd

doi:10.1111/dme.13328

Abstract

BackgroundChildren with neonatal diabetes often present with diabetic ketoacidosis and hence are at risk of cerebral oedema and subsequent long‐term neurological deficits. These complications are difficult to identify because neurological features can also occur as a result of the specific genetic aetiology causing neonatal diabetes.Case reportsWe report two cases of neonatal diabetes where ketoacidosis‐related cerebral oedema was the major cause of their permanent neurological disability. Case 1 (male, 18 years, compound heterozygous ABCC8 mutation) and case 2 (female, 29 years, heterozygous KCNJ11 mutation) presented with severe diabetic ketoacidosis at 6 and 16 weeks of age. Both had reduced consciousness, seizures and required intensive care for cerebral oedema. They subsequently developed spastic tetraplegia. Neurological examination in adulthood confirmed spastic tetraplegia and severe disability. Case 1 is wheelchair‐bound and needs assistance for transfers, washing and dressing, whereas case 2 requires institutional care for all activities of daily living. Both cases have first‐degree relatives with the same mutation with diabetes, who did not have ketoacidosis at diagnosis and do not have neurological disability.DiscussionKetoacidosis‐related cerebral oedema at diagnosis in neonatal diabetes can cause long‐term severe neurological disability. This will give additional neurological features to those directly caused by the genetic aetiology of the neonatal diabetes. Our cases highlight the need for increased awareness of neonatal diabetes and earlier and better initial treatment of the severe hyperglycaemia and ketoacidosis often seen at diagnosis of these children.

Highlights

The main cause of morbidity and mortality in childhoodonset diabetes is ketoacidosis [1]
Ketoacidosis-related cerebral oedema at diagnosis in neonatal diabetes can cause long-term severe neurological disability. This will give additional neurological features to those directly caused by the genetic aetiology of the neonatal diabetes
Our cases highlight the need for increased awareness of neonatal diabetes and earlier and better initial treatment of the severe hyperglycaemia and ketoacidosis often seen at diagnosis of these children

Summary

Discussion

These cases highlight that neurological disability in neonatal diabetes can occur as a result of diabetic ketoacidosis-related complications at diagnosis in addition to being a direct result of underlying genetic aetiology. The severity of disability in these cases may be attributable to late recognition of symptoms leading to severe ketoacidosis, the difficulty of neonatal fluid management and the vulnerability of the developing brain These two cases show that not all neurological deficits in people with neonatal diabetes are genetic in origin. This is relevant to genetic aetiologies where there is a variable phenotype, such as KCNJ11 and ABCC8 neonatal diabetes in which ~20% of people have marked neurological features [8]; neurological features attributed to the genetic change may not be the correct explanation for a person’s condition This information is important for clinicians when communicating the diagnosis to patient and family members, the likelihood of developing neurological disability in other family members who have inherited the same mutation. Our cases highlight the need for increased awareness of neonatal diabetes and earlier and better initial treatment of the severe hyperglycaemia and ketoacidosis often seen at diagnosis of these children

Introduction

Findings

Funding sources