Department of Pathology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, L471, Portland, OR 97239, USA.
Pediatr Nephrol. 2010 Jun;25(6):1181-4. doi: 10.1007/s00467-009-1426-0. Epub 2010 Jan 21.
Alagille syndrome is characterized by a paucity of interlobular bile ducts with chronic cholestasis, cardiac, skeletal, and eye abnormalities and is associated predominantly with JAG1 mutations. Various renal abnormalities have been sporadically described. The classic renal histopathology described in Alagille syndrome is mesangiolipidosis, with lipid deposits predominately confined to the mesangium and minimal deposition within the glomerular basement membrane (GBM). We report a 5-year-old girl with Alagille syndrome who presented with persistent subnephrotic proteinuria and renal tubular acidosis. A renal biopsy showed GBM irregularities (mimicking membranous glomerulonephritis), mesangial sclerosis, and focal segmental glomerulosclerosis (FSGS) on light microscopy. Electron microscopy revealed few lipid inclusions within the mesangium but extensive inclusions along the GBM. These findings are mostly consistent with those reported previously in Alagille syndrome. However, the histologic distribution of lipid vacuoles is seemingly reversed in this patient and is uniquely accompanied by FSGS, emphasizing the spectrum of renal histopathology seen in Alagille syndrome. The proteinuria observed in this patient is likely attributed to significant GBM lipid deposition, which over time may contribute to the development of FSGS.
Alagille 综合征的特征为肝内小胆管缺如伴慢性胆汁淤积、心脏、骨骼和眼部异常，主要与 JAG1 基因突变相关。各种肾脏异常也时有报道。Alagille 综合征经典的肾脏组织病理学表现为系膜脂沉积病，脂质沉积主要局限于系膜，肾小球基底膜（GBM）内沉积很少。我们报告一例 5 岁 Alagille 综合征女孩，表现为持续性亚肾病范围蛋白尿和肾小管性酸中毒。肾脏活检显示光镜下 GBM 不规则（类似膜性肾小球肾炎）、系膜硬化和局灶节段性肾小球硬化（FSGS）。电镜下显示系膜内仅有少量脂质包涵体，但 GBM 内有广泛包涵体。这些发现与先前报道的 Alagille 综合征一致。然而，该患者的脂质空泡组织学分布似乎相反，且独特地伴有 FSGS，强调了 Alagille 综合征的肾脏组织病理学谱。该患者的蛋白尿可能归因于 GBM 脂质的大量沉积，随着时间的推移可能导致 FSGS 的发生。
