Ozaltin Fatih, Heeringa Saskia, Poyraz Ceren Erdogan, Bilginer Yelda, Kadayifcilar Sibel, Besbas Nesrin, Topaloglu Rezan, Ozen Seza, Hildebrandt Friedhelm, Bakkaloglu Aysin
Unit of Nephrology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey.
Pediatr Nephrol. 2008 Mar;23(3):421-7. doi: 10.1007/s00467-007-0695-8. Epub 2007 Dec 5.
Distinct eye abnormalities have been described in children with nephrotic syndrome, particularly in diffuse mesangial sclerosis (i.e. Pierson syndrome). The aim of the study was to investigate whether there were any associated ocular anomalies in children with steroid-resistant nephrotic syndrome (SRNS), all of whom had revealed primary focal segmental glomerulosclerosis in biopsy. Thirty-three SRNS patients (16 male, 17 female) with a median age of 10.5 years (range 3-25 years) were enrolled in the study. Twenty steroid-sensitive nephrotic syndrome (SSNS) patients (ten male, ten female) with a median age of 8 years (range 3-15 years) served as controls. All SRNS patients were examined by mutational analysis for mutations in the NPHS2, WT1, and LAMB2 genes. Nine out of 33 SRNS patients (27.2%) showed various eye abnormalities. However, no abnormal ocular findings were detected in any of the SSNS patients. Abnormal eye findings detected in SRNS patients were anisometropic amblyopia (n = 4), Mittendorf's dots (n = 4), myopic astigmatism (n = 3) and exotropia (n = 1). Macular pigment changes (n = 1), posterior subcapsular opacities (n = 1) and cataract (n = 1) were considered as steroid-induced side effects. In four patients, more than one eye abnormality was found. Mutational analysis for the NPHS2, WT1 and LAMB2 genes revealed disease-causing mutations in 24.2% of patients. Homozygous NPHS2 mutations were detected in five patients (15.1%), all of whom had parental consanguinity. In three patients (9%) from non-consanguineous parents, heterozygous de novo WT1 mutations were detected as disease-causing mutations. No LAMB2 mutation was detected in any patient. While four out of five (80%) patients with homozygous NPHS2 mutations showed at least one abnormal ocular finding (i.e. Mittendorf's dot or anisometric amblyopia), none of the patients with a WT1 mutation had ocular involvement. In conclusion, ocular involvement may accompany SRNS caused by primary focal segmental glomerulosclerosis (FSGS). Ophthalmologic evaluation at the time of diagnosis might be beneficial to characterize further the spectrum of this possible association.
肾病综合征患儿，尤其是弥漫性系膜硬化（即皮尔逊综合征）患儿，已被描述有明显的眼部异常。本研究的目的是调查激素抵抗型肾病综合征（SRNS）患儿是否存在任何相关的眼部异常，所有这些患儿活检均显示原发性局灶节段性肾小球硬化。33例SRNS患者（男16例，女17例）纳入研究，中位年龄10.5岁（范围3 - 25岁）。20例激素敏感型肾病综合征（SSNS）患者（男10例，女10例）作为对照，中位年龄8岁（范围3 - 15岁）。所有SRNS患者均通过突变分析检测NPHS2、WT1和LAMB2基因的突变。33例SRNS患者中有9例（27.2%）出现各种眼部异常。然而，SSNS患者均未检测到眼部异常发现。SRNS患者检测到的眼部异常发现有屈光参差性弱视（n = 4）、米滕多夫氏点（n = 4）、近视散光（n = 3）和外斜视（n = 1）。黄斑色素改变（n = 1）、后囊下混浊（n = 1）和白内障（n = 1）被认为是激素引起的副作用。4例患者发现不止一种眼部异常。NPHS2、WT1和LAMB2基因的突变分析显示24.2%的患者存在致病突变。5例患者（15.1%）检测到纯合NPHS2突变，所有这些患者父母均为近亲结婚。3例（9%）非近亲结婚父母的患者检测到杂合新发WT1突变作为致病突变。所有患者均未检测到LAMB2突变。虽然5例纯合NPHS2突变患者中有4例（80%）至少有一项眼部异常发现（即米滕多夫氏点或屈光参差性弱视），但WT1突变患者均无眼部受累。总之,原发性局灶节段性肾小球硬化（FSGS）引起的SRNS可能伴有眼部受累。诊断时进行眼科评估可能有助于进一步明确这种可能关联的范围。
