Dupont Juliette, Pereira Carla, Medeira Ana, Duarte Rui, Ellard Sian, Sampaio Lurdes
Serviço de Genética, Hospital de Santa Maria, Lisboa, Portugal.
J Pediatr Endocrinol Metab. 2012;25(3-4):367-70. doi: 10.1515/jpem-2011-0191.
Permanent neonatal diabetes mellitus (PNDM) is a rare form of diabetes diagnosed within the first 6 months of life. Heterozygous activation mutations in KCNJ11, encoding the Kir6.2 subunit of the ATP-sensitive potassium (K(ATP)) channel, which acts as a key role in insulin secretion regulation, account for about half of the cases of PNDM. The majority of the patients represent isolated cases resulting from de novo mutations. Approximately 20% have associated neurologic features: the most severe form, which includes epilepsy and developmental delay, is called developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome and the milder form, with less severe developmental delay and without epilepsy, is designated intermediate DEND syndrome. Individuals with KCNJ11 mutations have been successfully transitioned from insulin to sulfonylurea (SU) therapy. Furthermore, there have been cases reported with variable improvement in neurological function following a successful switching. We describe a 12-year-old Portuguese girl with PNDM due to the previously reported R201C mutation in the KCNJ11 gene. Her medical history includes prematurity and moderate developmental delay. The mutation was inherited from her mother who has isolated PNDM. The patient was successfully transferred from insulin to SU, whereas her mother showed SU resistance. Despite good glycemic control, no improvements in the cognitive performance were verified. We present our experience in switching treatment from insulin to oral SUs in this family, and also discuss whether or not the girl's developmental delay is related with the Kir6.2 mutation. To our knowledge, this is the first Portuguese patient reported with successful transition to SU treatment.
永久性新生儿糖尿病（PNDM）是一种罕见的糖尿病形式，在出生后的前6个月内被诊断出来。编码ATP敏感性钾（K(ATP)）通道Kir6.2亚基的KCNJ11基因杂合激活突变在胰岛素分泌调节中起关键作用，约占PNDM病例的一半。大多数患者为新发突变导致的散发病例。约20%的患者伴有神经学特征：最严重的形式包括癫痫和发育迟缓，称为发育迟缓、癫痫和新生儿糖尿病（DEND）综合征；较轻的形式，发育迟缓较轻且无癫痫，称为中间型DEND综合征。携带KCNJ11突变的个体已成功从胰岛素治疗过渡到磺脲类（SU）药物治疗。此外，有报道称成功换药后神经功能有不同程度的改善。我们描述了一名12岁的葡萄牙女孩，因之前报道的KCNJ11基因R201C突变而患有PNDM。她的病史包括早产和中度发育迟缓。该突变遗传自患有散发性PNDM的母亲。患者成功从胰岛素治疗转换为SU治疗，而她的母亲对SU耐药。尽管血糖控制良好，但未观察到认知能力有改善。我们介绍了在这个家庭中从胰岛素治疗转换为口服SU治疗的经验，并讨论了该女孩的发育迟缓是否与Kir6.2突变有关。据我们所知，这是首例报道成功转换为SU治疗的葡萄牙患者。
