Long-term neurodevelopmental outcome in conservatively treated congenital hyperinsulinism.
BACKGROUND
Congenital hyperinsulinism (CH) is treated surgically in many centers (near-total and partial pancreatectomy for diffuse and focal disease respectively). Most patients treated with near-total pancreatectomy developed diabetes during childhood/puberty. CH patients are at increased risk of neurodevelopmental disorders, some being severe, which are reported to occur in 14-44% of patients from highly heterogenous cohorts. Over the last few decades, we have treated children with CH conservatively without surgery. The aim of this study was to assess the neurodevelopmental outcome of these patients.


METHODS
The study included 21 Ashkenazi CH medically treated patients: 11 homozygotes (diffuse disease) and 9 heterozygotes with mutations on the paternal allele (presumed focal disease). The mean age was 13.7 years (range 8-23). Neurodevelopmental outcomes were assessed by telephone interviews of parents, using a standard questionnaire. Closest age siblings of CH patients served as controls.


RESULTS
Ten CH patients had perinatal seizures of short duration. Four had post-neonatal seizures, which remitted entirely. During early childhood, four patients (19%) had hypotonia, eight (38%) had fine motor problems, seven (33%) had gross motor problems (clumsiness), and one had mild cerebral palsy. Three patients (14%) had speech problems. Eight patients required developmental therapy, compared to one in the control group. Most of these problems were resolved by age 4-5 years. At school age, all were enrolled in regular education, some excelled in their studies, 6 out of 21 patients (29%) had learning problems (2 out of 21 controls). None had overt diabetes.


CONCLUSIONS
Good neurodevelopmental outcome was observed in our conservatively treated CH patients, with no diabetes as reported in patients undergoing pancreatectomy.
Mazor-Aronovitch
K
K
Pediatric Endocrine Unit, Chaim Sheba Medical Center, Safra Children's Hospital, Tel Hashomer 52621, Israel. kineret@gmail.com
Gillis
D
D
Lobel
D
D
Hirsch
H J
HJ
Pinhas-Hamiel
O
O
Modan-Moses
D
D
Glaser
B
B
Landau
H
H
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001921:Brain / Q000254:growth & development; D002648:Child; D002657:Child Development / Q000502:physiology; D044903:Congenital Hyperinsulinism / Q000150:complications / Q000235:genetics / Q000628:therapy*; D002658:Developmental Disabilities / Q000209:etiology; D003920:Diabetes Mellitus / Q000209:etiology; D005500:Follow-Up Studies; D006801:Humans; D009154:Mutation; D009420:Nervous System / Q000254:growth & development*; D010180:Pancreatectomy / Q000009:adverse effects; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics; D064233:Sulfonylurea Receptors; D013997:Time Factors; D016896:Treatment Outcome
D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors