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.

Hypnosis control based on the minimum concentration of anesthetic drug for maintaining appropriate hypnosis.

This paper proposes a novel hypnosis control method using Auditory Evoked Potential Index (aepEX) as a hypnosis index. In order to avoid side effects of an anesthetic drug, it is desirable to reduce the amount of an anesthetic drug during surgery. For this purpose many studies of hypnosis control systems have been done. Most of them use Bispectral Index (BIS), another hypnosis index, but it has problems of dependence on anesthetic drugs and nonsmooth change near some particular values. On the other hand, aepEX has an ability of clear distinction between patient consciousness and unconsciousness and independence of anesthetic drugs. The control method proposed in this paper consists of two elements: estimating the minimum effect-site concentration for maintaining appropriate hypnosis and adjusting infusion rate of an anesthetic drug, propofol, using model predictive control. The minimum effect-site concentration is estimated utilizing the property of aepEX pharmacodynamics. The infusion rate of propofol is adjusted so that effect-site concentration of propofol may be kept near and always above the minimum effect-site concentration. Simulation results of hypnosis control using the proposed method show that the minimum concentration can be estimated appropriately and that the proposed control method can maintain hypnosis adequately and reduce the total infusion amount of propofol.

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.

Late-onset X-linked sideroblastic anemia following hemodialysis.

X-linked sideroblastic anemia (XLSA) is due to deficient activity of erythroid-specific 5-aminolevulinate synthase (ALAS2). We report here a patient who developed sideroblastic anemia at the age of 81 years while undergoing hemodialysis. The diagnosis of sideroblastic anemia was established by the presence of ringed sideroblasts in the bone marrow, and treatment with oral pyridoxine completely eliminated the ringed sideroblasts. We identified a novel point mutation in the fifth exon of this patient's ALAS2 gene, which resulted in an amino acid change at residue 159 from aspartic acid to asparagine (Asp159Asn). In vitro analyses of recombinant Asp159Asn ALAS2 revealed that this mutation accounted for the pyridoxine-responsiveness of this disease. The very late onset in this case of XLSA emphasizes that nutritional deficiencies caused either by dietary irregularities in the elderly or, as in this case, by maintenance hemodialysis therapy, may uncover occult inherited enzymatic deficiencies in the heme biosynthetic pathway.