Long-term neurodevelopmental outcome in conservatively treated congenital hyperinsulinism

Mazor-Aronovitch, Kineret; Gillis, David; Lobel, Dana; Hirsch, Harry J.; Pinhas‐Hamiel, Orit; Modan‐Moses, Dalit; Gläser, Benjamin; Landau, H

doi:10.1530/eje-07-0445

Cited by 51 publications

(46 citation statements)

References 24 publications

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“…Earlier recommendations of prompt subtotal pancreatectomy to reduce the risk of brain damage from hypoglycaemia are no longer supported for a number of reasons: i) focus ablation is sufficient to cure patients with focal disease (8), ii) some patients with diffuse CHI may be treated successfully by medication and eventually undergo clinical remission after months or even several years (40)(41)(42) and iii) subtotal pancreatectomy is complicated by an increased risk of subsequent diabetes and mild malabsorption (43). The switch towards a more conservative approach in diffuse CHI (if possible) and a rapid focal resection in focal CHI in many centres implies that a uniform definition of CHI as mild/ moderate or severe according to treatment modality may be questioned.…”

Section: Prevalencementioning

confidence: 99%

Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation.

Christesen

Tribble

Molven

et al. 2008

European Journal of Endocrinology

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Objective: Activating glucokinase (GCK) mutations are a rarely reported cause of congenital hyperinsulinism (CHI), but the prevalence of GCK mutations is not known. Methods: From a pooled cohort of 201 non-syndromic children with CHI from three European referral centres (Denmark, nZ141; Norway, nZ26; UK, nZ34), 108 children had no K ATP -channel (ABCC8/KCNJ11) gene abnormalities and were screened for GCK mutations. Novel GCK mutations were kinetically characterised. Results: In five patients, four heterozygous GCK mutations (S64Y, T65I, W99R and A456V) were identified, out of which S64Y was novel. Two of the mutations arose de novo, three were dominantly inherited. All the five patients were medically responsive. In the combined Danish and Norwegian cohort, the prevalence of GCK-CHI was estimated to be 1.2% (2/167, 95% confidence interval (CI) 0-2.8%) of all the CHI patients. In the three centre combined cohort of 72 medically responsive children without K ATP -channel mutations, the prevalence estimate was 6.9% (5/72, 95% CI 1.1-12.8%). All activating GCK mutations mapped to the allosteric activator site. The novel S64Y mutation resulted in an increased affinity for the substrate glucose (S 0.5 1.49G0.08 and 7.39G0.05 mmol/l in mutant and wild-type proteins respectively), extrapolating to a relative activity index of w22 compared with the wild type. Conclusion: In the largest study performed to date on GCK in children with CHI, GCK mutations were found only in medically responsive children who were negative for ABCC8 and KCNJ11 mutations. The estimated prevalence (w7%) suggests that screening for activating GCK mutations is warranted in those patients.

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Section: Prevalencementioning

confidence: 99%

Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation.

Christesen

Tribble

Molven

et al. 2008

European Journal of Endocrinology

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“…In case of diffuse HI, where all b-cells are involved throughout the pancreas, long-term and intensive medical treatment is the only alternative to the near-total pancreatectomy, which leads to recurrent post-operative hypoglycemias in 60% of patients and then insulin-dependent diabetes within a few years in all patients (7,8). Thus, the challenge for diazoxide-unresponsive diffuse HI is to find an efficient and well-tolerated long-term medical treatment, especially as progressive b-cells apoptosis may be responsible for spontaneous remission (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Successful treatment of congenital hyperinsulinism with long-acting release octreotide

Sang

Arnoux

Mamoune

et al. 2012

European Journal of Endocrinology

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Context: Congenital hyperinsulinism (HI) is a common cause of hypoglycemia in infancy. The medical treatment of diazoxide-unresponsive HI is based on a somatostatin analogue. Objective: This study aims at replacing three daily s.c. octreotide (Sandostatin, Novartis) injections by a single and monthly i.m. injection of long-acting release (LAR) octreotide (Sandostatin LP, Novartis) in HI patients. Subjects and method: LAR octreotide was injected every 4 weeks during 6 months and s.c. octreotide injections were stopped after the third injection of LAR octreotide. After this 6-month study, LAR octreotide was continued, with an average follow-up of 17 months. Ten HI pediatric patients unresponsive to diazoxide and currently treated with s.c. octreotide were included in the trial. Glycemias and other parameters (HbA1c, IGF1, height, weight, quality of life (QoL), and satisfaction) were monitored at each monthly visit. Results: For all ten patients, glycemias were maintained in the usual range, HbAlc (mean 5.5%; 95% CI: 4.6-6.2) and IGF1 (mean 89.7 ng/ml; 95% CI: 26-153) were unchanged. Patients gained height significantly (mean 2.7 cm; 95% CI: 1.9-3.4) and no side effect was noted during the study and the later follow-up. Plasma octreotide levels were stable under LAR octreotide. Parents' questionnaires of general satisfaction were highly positive whereas children's QoL evaluation remained unchanged. Conclusion: In these diazoxide-unresponsive HI patients, LAR octreotide was efficient, well tolerated and contributed to a clear simplification of the medical care.

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“…Steinkrauss et al [20] reported 68 patients with CH; one third had developmental delay which was more prevalent in surgical group. Mazor et al [21] studied 21 Ashkenazi children 12 with diffuse and 9 with focal disease; all of them received medical treatment. Most of the developmental problems resolved by school age and all children were enrolled in regular education.…”

Section: Discussionmentioning

confidence: 99%

Long Term Medical Treatment of Congenital Hyperinsulinemic Hypoglycemia

Ahmad¹

2014

JED

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Long-term neurodevelopmental outcome in conservatively treated congenital hyperinsulinism

Abstract: Background: Congenital hyperinsulinism (CH) is treated surgically in many centers (near

Cited by 51 publications

References 24 publications

Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation.

Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation.

Successful treatment of congenital hyperinsulinism with long-acting release octreotide

Long Term Medical Treatment of Congenital Hyperinsulinemic Hypoglycemia

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