Becker Johanna, Haas Nikolaus A, Vlaho Stefan, Heineking Beatrice, Wortmann Saskia B, Rabenhorst Dorothée, Thomas Clara, Brunet Theresa
Department of Pediatric Cardiology and Intensive Care, Klinikum der Universität München, LMU, Munich, Germany.
Department of Pediatrics, Altoetting-Burghausen, Altoetting, Germany.
Neuropediatrics. 2021 Oct;52(5):398-402. doi: 10.1055/s-0040-1722685. Epub 2021 Jan 14.
Cytosolic phosphoenolpyruvate carboxykinase (PEPCK) deficiency (MIM 261680, EC 4.1.1.32, encoded by PCK1) is a rare disorder of gluconeogenesis presenting with recurrent hypoglycemia, hepatic dysfunction, and lactic acidosis. We report on a previously healthy 3-year-old boy who was initially admitted under the suspicion of a febrile seizure during an upper airway infection. Diagnostic workup revealed hypoglycemia as well as a cerebral edema and ruled out an infection. After a complicated course with difficult to treat symptomatic seizures, the child died on the 5th day of admission due to progressive cerebral edema. The metabolic screening showed elevated urinary lactate and Krebs cycle intermediates in line with a primary or secondary energy deficit. Due to the unclear and fatal course, trio exome sequencing was initiated postmortem ("molecular autopsy") and revealed the diagnosis of cytosolic PEPCK deficiency based on the compound heterozygosity of a known pathogenic (c.925G > A, p.(Gly309Arg)) and a previously unreported (c.724G > A, p.(Gly242Arg)) variant in (NM_002591.3). Sanger sequencing ruled out the disease and carrier status in three older brothers. Molecular autopsy was performed due to the unclear and fatal course. The diagnosis of a cytosolic PEPCK deficiency not only helped the family to deal with the grief, but especially took away the fear that the siblings could be affected by an unknown disease in the same manner. In addition, this case increases the genetic and phenotypic spectrum of cytosolic PEPCK deficiency.
胞质磷酸烯醇式丙酮酸羧激酶（PEPCK）缺乏症（MIM 261680，EC 4.1.1.32，由PCK1编码）是一种罕见的糖异生障碍疾病，表现为反复低血糖、肝功能障碍和乳酸酸中毒。我们报告了一名此前健康的3岁男孩，他最初因上呼吸道感染疑似热性惊厥入院。诊断检查发现低血糖以及脑水肿，并排除了感染。在经历了复杂的病程，伴有难以治疗的症状性惊厥后，患儿于入院第5天因进行性脑水肿死亡。代谢筛查显示尿乳酸和三羧酸循环中间产物升高，符合原发性或继发性能量缺乏。由于病程不明且致命，死后进行了三联体全外显子测序（“分子尸检”），基于已知致病突变（c.925G＞A，p.(Gly309Arg)）和一个此前未报道的突变（c.724G＞A，p.(Gly242Arg)）在（NM_002591.3）中的复合杂合性，确诊为胞质PEPCK缺乏症。桑格测序排除了三个哥哥的患病及携带状态。由于病程不明且致命，进行了分子尸检。胞质PEPCK缺乏症的诊断不仅帮助这个家庭应对悲痛，尤其消除了他们对兄弟姐妹可能以同样方式受未知疾病影响的恐惧。此外，该病例增加了胞质PEPCK缺乏症的遗传和表型谱。
