Burg Daniel, Altarescu Gheona, Korman Stanley, Shteyer Eyal, May Dalit
Department of Military Medicine and "Tzameret," Faculty of Medicine, Hebrew University of Jerusalem, and Medical Corps, Israel Defense Forces, Jerusalem, Israel.
Medical Genetics Institute, Shaare Zedek Medical Center, Hebrew University Hadassah Medical School, Jerusalem, Israel.
Mol Genet Metab Rep. 2024 Dec 19;42:101175. doi: 10.1016/j.ymgmr.2024.101175. eCollection 2025 Mar.
Cytosolic phosphoenolpyruvate carboxykinase (PEPCK) is an enzyme encoded by the PCK1 gene and plays a rate limiting step in gluconeogenesis occurring mainly in the liver during prolonged fasting. Biallelic deficiency of this enzyme results in a rare inborn error of metabolism disorder (OMIM # 261680). The main clinical and laboratory manifestations include fasting hypoglycemia and lactic acidosis with urinary excretion of Tricarboxylic Acid (TCA) cycles metabolites, particularly fumarate. The initial presentation varies between individuals in terms of age at initial presentation and clinical manifestations, however clinical information is lacking as it was diagnosed so far in less than 30 patients with a total of 6 different mutations which are all either missense or splice variants. We describe the first homozygous frame-shift mutation in the PCK1 gene, leading to cytosolic PEPCK deficiency. This resulted in transient hypoglycemia and acute liver failure with extreme hyperferritinemia (>40,000 ng/ml) during the first days of life. This severe very early-onset presentation that was not described earlier expands our clinical and genetic spectrum of this rare metabolic disorder.
胞质磷酸烯醇式丙酮酸羧激酶（PEPCK）是一种由PCK1基因编码的酶，在长期禁食期间主要在肝脏中发生的糖异生过程中起限速作用。该酶的双等位基因缺陷导致一种罕见的先天性代谢紊乱疾病（OMIM # 261680）。主要的临床和实验室表现包括空腹低血糖和乳酸酸中毒，伴有三羧酸（TCA）循环代谢产物，特别是富马酸盐的尿排泄。最初的表现因个体而异，包括首次出现的年龄和临床表现，但由于迄今为止诊断的患者不到30例，共有6种不同的突变，均为错义突变或剪接变体，因此缺乏临床信息。我们描述了PCK1基因中的第一个纯合移码突变，导致胞质PEPCK缺乏。这导致在生命的最初几天出现短暂性低血糖和急性肝衰竭，并伴有极高的铁蛋白血症（>40,000 ng/ml）。这种早期严重的表现此前未被描述，扩展了我们对这种罕见代谢紊乱疾病的临床和遗传谱的认识。
