Mazor-Aronovitch K, Gillis D, Lobel D, Hirsch H J, Pinhas-Hamiel O, Modan-Moses D, Glaser B, Landau H
Pediatric Endocrine Unit, Chaim Sheba Medical Center, Safra Children's Hospital, Tel Hashomer 52621, Israel.
Eur J Endocrinol. 2007 Oct;157(4):491-7. doi: 10.1530/EJE-07-0445.
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.
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.
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.
Good neurodevelopmental outcome was observed in our conservatively treated CH patients, with no diabetes as reported in patients undergoing pancreatectomy.
在许多中心，先天性高胰岛素血症（CH）采用手术治疗（分别对弥漫性和局灶性疾病进行近全胰腺切除术和部分胰腺切除术）。大多数接受近全胰腺切除术治疗的患者在儿童期/青春期患上糖尿病。CH患者患神经发育障碍的风险增加，其中一些较为严重，据报道，在高度异质性队列中的患者中，14% - 44%会出现这种情况。在过去几十年里，我们对CH患儿进行了非手术保守治疗。本研究的目的是评估这些患者的神经发育结局。
该研究纳入了21例接受药物治疗的阿什肯纳兹CH患者：11例纯合子（弥漫性疾病）和9例父本等位基因有突变的杂合子（推测为局灶性疾病）。平均年龄为13.7岁（范围8 - 23岁）。通过电话访谈父母，使用标准问卷评估神经发育结局。CH患者年龄最相近的兄弟姐妹作为对照。
10例CH患者有短期围产期癫痫发作。4例有新生儿期后癫痫发作，且完全缓解。在幼儿期，4例患者（19%）有肌张力减退，8例（38%）有精细运动问题，7例（33%）有大运动问题（笨拙），1例有轻度脑瘫。3例患者（14%）有言语问题。8例患者需要发育治疗，而对照组为1例。这些问题大多在4 - 5岁时得到解决。在学龄期，所有患者都进入正规教育，一些学生成绩优异，21例患者中有6例（29%）有学习问题（21例对照中有2例）。无一例有明显糖尿病。
在我们保守治疗的CH患者中观察到良好的神经发育结局，且没有出现胰腺切除术后患者所报道的糖尿病情况。
