Purpose of Review

This review summarizes current understanding of generalized arterial calcification of infancy (GACI), emphasizing pathophysiology, clinical presentation, and approaches and controversies in management.

Recent Findings

Identification of causative ENPP1 mutations revealed that GACI arises from deficiencies in inorganic pyrophosphate (leading to calcifications) and adenosine monophosphate (leading to intimal proliferation). Identification of genotypic and phenotypic overlap with pseudoxanthoma elasticum and autosomal recessive hypophosphatemic rickets further advanced understanding of GACI as a complex, multisystemic disease. Clinical data is limited to small, retrospective samples; it is therefore unknown whether commonly used medications, such as bisphosphonates and hypophosphatemia treatment, are therapeutic or potentially harmful. ENPP1-Fc replacement represents a promising approach warranting further study.

Summary

Knowledge gaps in natural history place clinicians at high risk of assigning causality to interventions that are correlated with changes in clinical status. There is thus a critical need for improved natural history studies to develop and test targeted therapies.

中文翻译：

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婴儿期广义动脉钙化：新见解、争议和管理方法。

审查目的

本综述总结了目前对婴儿全身动脉钙化 (GACI) 的理解，强调了病理生理学、临床表现以及管理方法和争议。

最近的发现

致病ENPP1突变的鉴定表明，GACI 是由无机焦磷酸盐（导致钙化）和一磷酸腺苷（导致内膜增殖）的缺陷引起的。确定与弹性假黄瘤和常染色体隐性低磷性佝偻病的基因型和表型重叠进一步加深了对 GACI 作为一种复杂的多系统疾病的理解。临床数据仅限于小型回顾性样本；因此，目前尚不清楚常用药物（如双膦酸盐和低磷血症治疗）是否具有治疗作用或可能有害。ENPP1-Fc 替代是一种有前途的方法，值得进一步研究。

概括

自然史方面的知识空白使临床医生面临将因果关系分配给与临床状态变化相关的干预措施的高风险。因此，迫切需要改进自然史研究来开发和测试靶向疗法。