Steroid-resistant nephrotic syndrome as the initial presentation of nail-patella syndrome: a case of a de novo LMX1B mutation.

BACKGROUND: Nail-patella syndrome (NPS) is an autosomal dominant disorder caused by mutations in the LMX1B gene and is characterized by nail dysplasia, skeletal abnormalities, and nephropathy. We herein report a case of steroid-resistant nephrotic syndrome (SRNS) prior to overt orthopedic symptoms in a patient with NPS. CASE PRESENTATION: A 24-year-old woman presented to our hospital with knee pain. She had poorly developed nails, hypoplastic patellas, dislocation of the elbows, and iliac horns in the pelvis. At the age of 7, she developed nephrotic syndrome and was diagnosed with primary focal segmental glomerulosclerosis by renal biopsy. She received long-term corticosteroid therapy with no obvious response. Her clinical course and orthopedic manifestations indicated NPS, and a genetic analysis showed a de novo mutation in the LMX1B gene (c.819 + 1G > A). Nephropathy in this case was considered to be associated with NPS. Therefore, we discontinued corticosteroids without the exacerbation of nephrotic syndrome. CONCLUSIONS: Patients with NPS may develop nephrotic syndrome prior to overt orthopedic symptoms and only show non-specific findings in renal biopsy at an early stage of NPS nephropathy. Hereditary nephrotic syndrome, often presenting as childhood-onset SRNS, may also be difficult to diagnose in patients with the following conditions: renal symptoms prior to overt extrarenal symptoms, de novo mutations, and non-specific findings in renal biopsy. Therefore, in the management of SRNS in children, we need to reconsider the possibility of hereditary diseases such as NPS even without a family history.

A case of idiopathic nodular glomerulosclerosis with fibrin caps.

We report a case of idiopathic nodular glomerulosclerosis (ING) mimicking diabetic Kimmelstiel-Wilson glomerulopathy. A 72-year-old man suffering from nephritic syndrome and renal dysfunction had no prior history of diabetes mellitus, but had impaired glucose tolerance and a history of hypertension and smoking. A kidney biopsy showed increased mesangial matrix with Kimmelstiel-Wilson-like nodules, glomerular basement membrane thickening and capillary microaneurysms. Additionally, a large amount of fibrin caps detectable as electron-dense subendothelial material by electron microscopy were observed. Although ING with fibrin caps has been rarely reported, the large number of fibrin caps seen in this case may be due to the advanced clinical stage.

Intramembranous microspherical structures in focal segmental glomerulosclerosis.

A 45-year-old male had proteinuria for 3 years. For persistent proteinuria over 2 g/day, he underwent renal biopsy. Light microscopy revealed focal segmental glomerulosclerosis together with diffuse capillary wall thickening. Periodic acid methenamine silver (PAM) staining showed a prominent bubbly appearance without spike formation could be found in almost all capillary walls. Electron microscopy revealed many microspheres measuring 50-70 nm in diameter distributed in diffuse and global fashion together with the thickened glomerular basement membrane. A few cytoplasmic processes of the podocytes showed infolding to the GBM. The patient exhibited no symptoms and no physical and serological findings suggesting autoimmune disease, such as systemic lupus erythematosus or Sjögren's syndrome. Therefore, the present case is important, because the peculiar microstructure in the GBM was noted in focal segmental glomerulosclerosis, which has never been reported in the literature.