Hanna Christian, Potretzke Theodora A, Chedid Maroun, Rangel Laureano J, Arroyo Jennifer, Zubidat Dalia, Tebben Peter J, Cogal Andrea G, Torres Vicente E, Harris Peter C, Sas David J, Lieske John C, Milliner Dawn S, Chebib Fouad T
Division of Pediatric Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
Division of Radiology, Mayo Clinic, Rochester, Minnesota.
Kidney Med. 2022 Jan 24;4(3):100419. doi: 10.1016/j.xkme.2022.100419. eCollection 2022 Mar.
RATIONALE & OBJECTIVE: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare monogenic disorder caused by pathogenic variants. HHRH is characterized by kidney phosphate wasting, hypophosphatemia, hypercalciuria, an elevated 1,25-dihydroxyvitamin D level, nephrocalcinosis, and urinary stone disease. Previously, we reported a 100% prevalence of kidney cysts in the related CYP24A1 deficiency. Thus, in the current study, we characterized cysts' presence in HHRH, another monogenic cause of hypercalciuria, nephrocalcinosis, and urinary stone disease.
Case series.
SETTING & PARTICIPANTS: Medical records from the Mayo Clinic and the Rare Kidney Stone Consortium monogenic stone disease database were queried for patients with a genetically confirmed HHRH diagnosis. The number, sizes, and locations of kidney cysts in each patient were recorded.
Twelve patients with pathogenic variants were identified (7 monoallelic, 5 biallelic). Of these, 5 (42%) were males, and the median (Q1, Q3) ages were 16 years (13, 35 years) at clinical presentation and 42 years (20, 57 years) at genetic confirmation. Kidney cysts were present in 9 of 12 (75%) patients, and the median (Q1, Q3) age at first cyst detection was 41 years (13, 50 years). The median number of cysts per patient was 2.0 (0.5, 3.5). Fifty percent of adult patients had a cyst number that exceeded the 97.5th percentile of an age- and sex-matched control population. All children had at least 2 or more total cysts. None had a family history of cystic kidney disease.
Retrospective study, possible selection bias, single-center experience.
A strong association between HHRH and kidney cysts was observed. Similarities in the biochemical profiles of HHRH and CYP24A1 deficiency suggest elevated active vitamin D and hypercalciuria may be potential cystogenic factors. Further studies are needed to understand how genetic changes in favor cyst formation.
遗传性低磷血症伴高钙尿症（HHRH）是一种由致病变异引起的罕见单基因疾病。HHRH的特征是肾磷酸盐流失、低磷血症、高钙尿症、1,25-二羟维生素D水平升高、肾钙质沉着症和尿路结石病。此前，我们报道了相关CYP24A1缺乏症患者肾囊肿的患病率为100%。因此，在本研究中，我们对HHRH（高钙尿症、肾钙质沉着症和尿路结石病的另一种单基因病因）中囊肿的存在情况进行了特征描述。
病例系列研究。
查询了梅奥诊所和罕见肾结石联盟单基因结石病数据库中的病历，以寻找基因确诊为HHRH的患者。记录了每位患者肾囊肿的数量、大小和位置。
共识别出12例携带致病变异的患者（7例单等位基因，5例双等位基因）。其中，5例（42%）为男性，临床表现时的中位年龄（第一四分位数，第三四分位数）为16岁（13岁，35岁），基因确诊时为42岁（20岁，57岁）。12例患者中有9例（75%）存在肾囊肿，首次发现囊肿时的中位年龄（第一四分位数，第三四分位数）为41岁（13岁，50岁）。每位患者囊肿的中位数量为2.0（0.5，3.5）。50%的成年患者囊肿数量超过了年龄和性别匹配的对照人群的第97.5百分位数。所有儿童的囊肿总数至少为2个或更多。均无多囊肾病家族史。
回顾性研究，可能存在选择偏倚，单中心经验。
观察到HHRH与肾囊肿之间存在强关联。HHRH和CYP24A1缺乏症生化特征的相似性表明，活性维生素D升高和高钙尿症可能是潜在的囊肿形成因素。需要进一步研究以了解有利于囊肿形成的基因变化情况。
