PIGO-CDG: A case study with a new genotype, expansion of the phenotype, literature review, and nosological considerations.
PIGO-CDG: A case study with a new genotype, expansion of the phenotype, literature review, and nosological considerations.
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DOI：
10.1002/jmd2.12396
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发表时间：
2023-11
期刊：
影响因子：
--
通讯作者：
Grange, Dorothy K
中科院分区：
文献类型：
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作者：
Starosta, Rodrigo Tzovenos;Kerashvili, Nino;Pruitt, Cassandra;Schultz, Matthew J;Boyer, Suzanne W;Morava, Eva;Lasio, Maria Laura Duque;Grange, Dorothy K
磷脂酰肌醇葡聚糖锚定O类蛋白(PIGO)酶是糖基化磷脂酰肌醇(GPI)生物合成的重要步骤，对多种蛋白质的膜锚定至关重要。Pigo的双等位致病变异导致先天性糖基化紊乱(CDG)，其特征是全球发育迟缓，血清碱性磷酸酶水平升高，大多数患者的先天性异常包括肛门直肠、生殖泌尿系统和肢体畸形；这种表型被交替称为“Mabry综合征”或“高磷酸盐伴智力发育障碍综合征2”。我们报告一位22个月大的女性因新的野猪变异引起的野猪缺乏症。除了Mabry综合征的表型外，我们的患者还伴有间歇性低血糖和功能性高胰岛素血症的体征，严重的分泌性腹泻，以及伴有病理性骨折的骨量减少，因此有可能扩大这种疾病的已知表型，尽管需要更多的研究来证实这些联系。我们还提供了最新的文献回顾，并建议将猪缺乏的命名统一为“猪-CDG”，这反映了它的病理生理学和在代谢紊乱和先天性糖基化障碍的广泛范围内的位置。
The phosphatidylinositol glycan anchor biosynthesis class O protein (PIGO) enzyme is an important step in the biosynthesis of glycosylphosphatidylinositol (GPI), which is essential for the membrane anchoring of several proteins. Bi‐allelic pathogenic variants in PIGO lead to a congenital disorder of glycosylation (CDG) characterized by global developmental delay, an increase in serum alkaline phosphatase levels, congenital anomalies including anorectal, genitourinary, and limb malformations in most patients; this phenotype has been alternately called “Mabry syndrome” or “hyperphosphatasia with impaired intellectual development syndrome 2.” We report a 22‐month‐old female with PIGO deficiency caused by novel PIGO variants. In addition to the Mabry syndrome phenotype, our patient's clinical picture was complicated by intermittent hypoglycemia with signs of functional hyperinsulinism, severe secretory diarrhea, and osteopenia with a pathological fracture, thus, potentially expanding the known phenotype of this disorder, although more studies are necessary to confirm these associations. We also provide an updated review of the literature, and propose unifying the nomenclature of PIGO deficiency as “PIGO‐CDG,” which reflects its pathophysiology and position in the broad scope of metabolic disorders and congenital disorders of glycosylation.