Odom John, Gieron-Korthals Maria, Shulman Dorothy, Newkirk Patricia, Prijoles Eloise, Sanchez-Valle Amarilis
USF Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, USA.
Department of Pediatrics, USF Health South Tampa Center for Advanced Healthcare, 2 Tampa General Circle, Tampa, FL, 33606, USA.
J Med Case Rep. 2016 Feb 2;10:25. doi: 10.1186/s13256-016-0811-0.
Hyperinsulinism-hyperammonemia syndrome is the second most common cause of congenital hyperinsulinism and is easily treated with diazoxide; however, the symptoms in our patient were very difficult to control with typical medical therapy. To the best of our knowledge, neither our patient's mutation, nor a case of hyperinsulinism-hyperammonemia presenting with dysmorphic features and intrauterine growth restriction has previously been reported.
We describe a 2-year-old Hispanic girl with an unusual presentation of dysmorphic features and intrauterine growth restriction who was later found to have hyperinsulinism-hyperammonemia syndrome. Chromosomal microarray analysis revealed no copy number variants but demonstrated a high density of noncontiguous regions of homozygosity consistent with limited outbreeding. Sequencing of her GLUD1 gene revealed a previously undescribed mutation of cytosine to thymine at position 1519 resulting in an amino acid change of histidine to tyrosine at position 507. Although no functional studies were performed, function prediction tools in combination with our patient's phenotype support the hypothesis that the mutation is deleterious. Despite treatment with a maximum dose of diazoxide (15 mg/kg/day), phenobarbital (8.5 mg/kg/day divided twice daily) and a protein-restricted diet, she has global developmental delay, and continues to have seizures and recurrent episodes of hypoglycemia.
It remains unclear if her clinical presentation can be solely explained by hyperinsulinism-hyperammonemia syndrome or is the result of an undiagnosed recessive disorder related to her homozygosity. It is our hope that clinicians may learn from our patient when formulating treatment plans for refractory cases of hyperinsulinism-hyperammonemia and avoid the morbidities associated with delayed diagnosis and treatment.
高胰岛素血症 - 高氨血症综合征是先天性高胰岛素血症的第二大常见病因，使用二氮嗪治疗很容易；然而，我们患者的症状用典型的药物治疗很难控制。据我们所知，此前尚未报道过我们患者的突变情况，也没有出现过伴有畸形特征和宫内生长受限的高胰岛素血症 - 高氨血症病例。
我们描述了一名2岁的西班牙裔女孩，她有不寻常的畸形特征和宫内生长受限表现，后来被发现患有高胰岛素血症 - 高氨血症综合征。染色体微阵列分析未发现拷贝数变异，但显示出与有限的远亲繁殖一致的高密度非连续纯合区域。对她的GLUD1基因进行测序，发现第1519位的胞嘧啶突变为胸腺嘧啶，这是一个此前未被描述的突变，导致第507位的组氨酸变为酪氨酸。尽管未进行功能研究，但功能预测工具结合我们患者的表型支持该突变有害的假设。尽管使用了最大剂量的二氮嗪（15毫克/千克/天）、苯巴比妥（8.5毫克/千克/天，分两次服用）和蛋白质限制饮食进行治疗，但她仍有全面发育迟缓，并且继续有癫痫发作和反复低血糖发作。
目前尚不清楚她的临床表现是否仅由高胰岛素血症 - 高氨血症综合征解释，还是与她的纯合性相关的未确诊隐性疾病的结果。我们希望临床医生在为高胰岛素血症 - 高氨血症难治性病例制定治疗计划时能从我们的患者身上吸取教训，避免与诊断和治疗延迟相关的发病率。
