Reinhart S C, Norden A G, Lapsley M, Thakker R V, Pang J, Moses A M, Frymoyer P A, Favus M J, Hoepner J A, Scheinman S J
Department of Medicine, SUNY Health Science Center, Syracuse 13210.
J Am Soc Nephrol. 1995 Jan;5(7):1451-61. doi: 10.1681/ASN.V571451.
X-linked recessive nephrolithiasis (XRN) was described in a large kindred in which nephrolithiasis; proximal tubular dysfunction, proteinuria, nephrocalcinosis, and renal failure occur only in males. Carrier females are asymptomatic, but formal studies of them have not been done. The gene for XRN has been mapped to the pericentromeric region of the X chromosome, close to the loci for several eye disease genes. We studied six affected males, 13 carrier females, and 25 normal members of this family including 7 females whose genetic haplotype predicted them to be carriers. Studies were done in the Clinical Research Unit on a diet containing 400 mg of calcium and 2 g of sodium, and by an additional outpatient urine collection was obtained on a 1-g calcium intake. Hypercalciuria occurred in five of six affected males, 4 of 12 carrier females, and three of seven predicted carriers. Significant proteinuria was present in all affected males and in no other subjects. Low-molecular-weight proteinuria was present in all affected males: the excretion of alpha 1-microglobulin exceeded normal by 3- to 14-fold, of beta 2-microglobulin exceeded normal by 100- to 400-fold, and of retinol-binding protein exceeded normal by 1,000- to 3,000-fold. The excretion of these proteins was less strikingly elevated in carrier females, but the excretion of alpha 1-microglobulin was abnormal in 9 of 15 carriers, beta 2-microglobulin was abnormal in 12 of 15, and retinolbinding protein in was abnormal 12 of 13, and this pattern was similar in predicted carriers. The urinary concentrating ability was abnormal in four affected males with renal insufficiency but normal in all other subjects. Urinary wasting of potassium, phosphorous, and glucose occurred infrequently, and no subject was hypouricemic. Formal ophthalmologic studies were normal in five affected males. Thus, the most consistent urinary abnormalities in XRN are hypercalciuria and low-molecular-weight proteinuria, the latter of which appears to be a marker for the carrier state.
X连锁隐性肾结石病（XRN）在一个大家族中被描述，在这个家族中，肾结石、近端肾小管功能障碍、蛋白尿、肾钙质沉着症和肾衰竭仅发生在男性身上。携带致病基因的女性没有症状，但尚未对她们进行正式研究。XRN基因已被定位到X染色体的着丝粒周围区域，靠近几个眼病基因的位点。我们研究了这个家族的6名患病男性、13名携带致病基因的女性和25名正常成员，其中包括7名根据遗传单倍型预测为携带者的女性。研究在临床研究室进行，受试者食用含有400毫克钙和2克钠的饮食，并另外在门诊收集了摄入1克钙时的尿液。6名患病男性中有5名出现高钙尿症，12名携带致病基因的女性中有4名出现高钙尿症，7名预测为携带者的女性中有3名出现高钙尿症。所有患病男性均出现显著蛋白尿，其他受试者均未出现。所有患病男性均出现低分子量蛋白尿：α1-微球蛋白的排泄量比正常水平高出3至14倍，β2-微球蛋白的排泄量比正常水平高出100至400倍，视黄醇结合蛋白的排泄量比正常水平高出1000至3000倍。这些蛋白质的排泄量在携带致病基因的女性中升高程度不那么明显，但在15名携带者中有9名α1-微球蛋白排泄异常，15名中有12名β2-微球蛋白排泄异常，13名中有12名视黄醇结合蛋白排泄异常，在预测为携带者的女性中也有类似模式。4名患有肾功能不全的患病男性的尿液浓缩能力异常，但所有其他受试者的尿液浓缩能力正常。尿液中钾、磷和葡萄糖的流失很少见，没有受试者出现低尿酸血症。5名患病男性的正规眼科检查正常。因此，XRN中最一致的尿液异常是高钙尿症和低分子量蛋白尿，后者似乎是携带致病基因状态的一个标志物。
