The co-existence of Fabry and celiac diseases: a case report

We present a patient with Fabry disease with remarkable diagnostic findings and gluten-sensitive enteropathy. An 11-year-old girl was admitted to hospital with weight loss, anorexia, nausea, vomiting, flank pain, acroparesthesia, and painful extremities. Her mother had end-stage renal failure secondary to Fabry disease. On physical examination, she had growth retardation. Ophthalmological examination showed characteristic whorl-like corneal opacities and Fabry disease was confirmed with low -galactosidase A (-gal A) activity. Her painful attacks were treated with carbamazepine, but vomiting and nausea continued. Laboratory studies revealed positive serum anti-endomysium and anti-gliadin antibodies. Small intestinal biopsy showed subtotal villous atrophy compatible with gluten-sensitive enteropathy. Following treatment with a gluten-free diet, her gastrointestinal symptoms completely disappeared within a few weeks and then she had catch-up growth. In her long-term follow-up, proteinuria appeared and renal involvement was confirmed by characteristic renal biopsy findings. Following these clinicopathological findings, enzyme replacement therapy was started. In conclusion, although heterozygous females can be asymptomatic or are expected to have a mild course of the disease, a severe clinical course in our patient in the 2nd decade is of particular interest. In addition, Fabry disease occurring with gluten-sensitive enteropathy, a very rare co-existence, is emphasized.     

A case of minimal change disease in a Fabry patient

Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the GLA gene and deficiency in α-galactosidase A activity. Glycosphingolipids accumulation causes renal injury that manifests early during childhood as tubular dysfunction and later in adulthood as proteinuria and renal insufficiency. Nephrotic syndrome as the first evidence of Fabry-related kidney damage is rare. We report the case of a teenager with known Fabry disease and normal renal function who developed acute nephrotic syndrome. He was found to have typical glycosphingolipids accumulation with no other findings suggestive of alternative causes of nephrotic syndrome on kidney biopsy. After treatment with enzyme replacement therapy and oral steroids, he went into complete remission from nephrotic syndrome, a response that is atypical for Fabry disease patients who develop heavy proteinuria as a result of longstanding disease and chronic renal injury. The nephrotic syndrome in this patient appears to have developed secondary to minimal change disease. We recommend considering immunotherapy in addition to enzyme replacement therapy in those patients with confirmed Fabry disease and acute nephrotic syndrome with clinical and microscopic findings suggestive of minimal change disease.     

Fabry disease and nephrogenic diabetes insipidus

Fabry disease is a lysosomal storage disorder with kidney involvement. The initial manifestation of kidney disease is often impaired urinary concentrating ability in adolescence or young adulthood. We describe a boy diagnosed prenatally with Fabry disease who presented with polyuria, polydipsia, hypertension, hypokalaemia and proteinuria at 7 years of age. A formal water-deprivation test followed by vasopressin challenge confirmed nephrogenic diabetes insipidus. A renal biopsy revealed findings typical of Fabry disease. Angiotensin converting-enzyme therapy resulted in rapid improvement of symptoms, normalization of blood pressure and resolution of hypokalaemia and proteinuria. This child is the youngest reported Fabry disease patient with documented renal pathology and clinical manifestations of hypertension, proteinuria and nephrogenic diabetes insipidus.     

Focal and segmental glomerular sclerosis (FSGS) in a man and a woman with Fabry's disease

We describe a man and a woman with Fabry's disease. Renal biopsies showed late and early stages respectively of focal and segmental glomerulosclerosis (FSGS) and vascular changes. Clinically the hemizygous patient had advanced renal disease with nephrotic range proteinuria and serum creatinine 122 micromol/l. The female carrier had minimal albuminuria, borderline GFR with a normal serum creatinine, acroparesthesias, moderate fatigue, tinnitus and headache accompanied by ischemic cerebral lesions. Enzyme replacement therapy (ERT) was initiated according to our Fabry protocol, partly due to the renal morphologic findings. We conclude that FSGS and vascular changes may be an early morphologic finding in Fabry's disease, even in patients with subtle albuminuria. The potential role of FSGS as a marker of progressive renal disease in some Fabry patients is discussed. As FSGS and vascular changes obviously may exist across a wide range of clinical presentations and have potential prognostic implications, we suggest that a renal biopsy should be performed prior to enzyme replacement therapy in all adult Fabry patients with proteinuria of various levels. Efforts should be made to develop a scoring system to evaluate potential histologic markers. Protocol biopsies may have therapeutic implications and may provide valuable information in the evaluation of start and dosing of ERT.     

Fabry Disease in a Renal Allograft

Incidental findings of rare diseases in organ donors can be seen in allograft biopsies that may have profound implications for the recipient and for the donor and their family. Fabry disease is an X-linked recessive lipid storage disease with cardiovascular, renal and lenticular abnormalities. Phenotypic expression in female heterozygote carriers depends on lyonization. Minimal data exists on outcomes of transplanted kidneys from carriers of Fabry disease. We report a patient with ESRD secondary to focal sclerosis who received a HLA-identical transplant from her sister whose pretransplant donor work up was completely negative. Post-transplant, while pregnant, the recipient developed increasing proteinuria and was biopsied. The biopsy showed extensive myelin figures consistent with Fabry disease. Subsequent genetic, enzymatic and pedigree analysis confirmed the diagnosis in the recipient, the donor and the donor's son. Two years post-transplant the patient continues to have non-nephrotic range proteinuria with normal serum creatinine.     

A case of ischemic mitral regurgitation treated by mitral annuloplasty (MAP) and coronary artery bypass grafting (CABG)]

A 79-year-old woman with a previous history of myocardial infarction, suffered acute myocardial infarction again. A coronary angiogram revealed triple vessel disease, and a left ventriculogram showed severe mitral regurgitation. The patient fell into cardiogenic shock after cardiac catheterization, and IABP was started. She underwent MAP and saphenous vein bypass grafting to the left anterior descending coronary artery and left circumflex coronary artery. Although the postoperative course was complicated by acute renal failure and respiratory dysfunction, the patient recovered from the operation and was discharged on the 137th postoperative day. Since the operative mortality of conventional valve replacement combined with CABG in ischemic mitral regurgitation has been high, we preferred MAP for this case.     

A case of nephrotic syndrome associated with myasthenia gravis and malignant thymoma]

A 26-year-old woman who presented facial and lower leg edema associated with massive proteinuria was admitted to our hospital in February 1992. Nine months before this admission, she exhibited myasthenia gravis and malignant thymoma, and underwent total thymectomy. On admission, there was no symptom of myasthenia gravis. She was diagnosed as having nephrotic syndrome and the first renal biopsy was performed. The histological findings showed membranous nephropathy. Immunofluorescent microscopy revealed that IgG and C3 were stained in a granular pattern in the periphery, and subepithelial deposits were observed in the basement membrane of the glomerulus by electron microscopy. With the administration of prednisolone, proteinuria disappeared and the nephrotic syndrome remitted. She was admitted again in January 1993 due to proteinuria and lower leg edema following cystitis. The findings of the second renal biopsy were unremarkable. She was administered cyclosporin A to improve the nephrotic syndrome and to reduce the side effects of prednisolone. The proteinuria disappeared again and this effect was dependent on the dose of cyclosporin A. Since the first administration, no symptoms of myasthenia gravis or malignant thymoma have been observed. The relationships among myasthenia gravis, malignant thymoma and nephrotic syndrome were examined. Although the first renal biopsy findings showed membranous nephropathy, from the therapeutic responses of both prednisolone and cyclosporin A, the main course of proteinuria in this case may have been due to minimal change nephrotic syndrome. We consider this case of nephrotic syndrome to be important considering its etiology and the relationship between the histological findings and its clinical course.     

Long-term follow-up of membranoproliferative glomerulonephritis type II and pregnancy: a case report

A 24-year-old female was diagnosed as having membranoproliferative glomerulonephritis type II (or dense deposit disease), 11 years prior to becoming pregnant. The patient's first renal biopsy was performed 5 years after the onset of her renal symptoms. This biopsy was compared to a second renal biopsy taken just before the patient became pregnant. The second renal biopsy only showed a slight progression in the disease process. During the course of pregnancy, neither renal insufficiency nor hypertension were clinically evident. However, both an increase in proteinuria and a transient hypoalbuminemia were observed. The pregnancy, labor and delivery, and postpartum course for both the mother and child were without complications. Cases of membranoproliferative glomerulonephritis type I and pregnancy have been reported. However, to our knowledge, there are few reports documenting the outcome of pregnancy when a patient has membranoproliferative glomerulonephritis type II. We suggest that it is possible for a patient with membranoproliferative glomerulonephritis type II to have an uneventful pregnancy if she has neither hypertension nor renal insufficiency.     

A case of idiopathic chronic interstitial nephritis progressed to renal failure without proteinuria nor hematuria]

A case of idiopathic interstitial nephritis who underwent to chronic renal failure without history of hematuria nor proteinuria is discussed. A 46 years old woman who showed gradually elevation of serum creatinine (1.3-2.5 mg/dl) admitted on our hospital. On occasions of pregnancy, health examination or hospital visit, she has never been pointed out hematuria nor proteinuria. Immunological disorders such as SLE, metabolic diseases, urinary tract obstruction and chronic urinary tract infection were excluded by the examinations after admission. Because of the severe enzymuria (beta 2-microglobulin, N-acetyl glucosaminidase), chronic interstitial nephritis was considered, and renal biopsy was performed. Severe tubulointerstitial changes were observed histologically, however, glomerular damage was comparatively mild. From these results, she was diagnosed idiopathic chronic tubulointerstitial nephritis. In this case, hematuria and proteinuria were absent until severe renal dysfunction. This may be caused by that inflammation was located to the tubulointerstitial area. The observation of enzymuria seemed to be important to diagnosis and follow-up of the interstitial nephritis.     

Other glomerular pathologies in three patients with diabetes mellitus

Diabetic nephropathy is the common cause of end stage renal disease in diabetes mellitus. But other glomerular pathologies have been also described in diabetic patients. We described 3 cases with diabetes mellitus and other glomerular diseases. Case I: A 59-year-old male patient with type 2 diabetes mellitus for 4 years was evaluated for generalized edema. Physical examination showed pretibial edema and no diabetic retinopathy. The cause of nephrotic syndrome was membranoproliferative glomerulonephritis. Conservative therapy could not control the severe proteinuria and renal dysfunction. With corticosteroid and cyclophosphamide therapy partial remission was obtained. Case II: A 46-year-old diabetic woman was evaluated for severe proteinuria. Diabetic retinopathy was not found on her funduscopic examination. Mesangioproliferative glomerulonephritis was found on renal biopsy. Proteinuria did not regress with conservative therapy and corticosteroid and cyclophosphamide. Case III: A 48-year-old male patient with diabetes mellitus type 2 for 2 years was admitted to the hospital because of nephrotic syndrome and weakness. At another hospital his diagnosis with biopsy showed minimal change disease. He was treated with corticosteroid since 3 months. His renal biopsy was reevaluated and found amyloid deposition but not diabetic nephropathy or minimal change disease. In diabetic patients, nondiabetic nephropathy is not uncommon and it was reported as common as about 30%. In addition to therapy for diabetes mellitus these patients can need specific therapy.     

Pregnancy outcome in nephrotic syndrome with mixed connective tissue disease

We describe two pregnancies of a young woman with mixed connective tissue disease. In June 1983, she was diagnosed as having Raynaud's phenomenon, arthralgia, and proteinuria. She then developed nephrotic syndrome. Methylprednisolone was initially prescribed at a large dose of 1 g/day which was slowly tapered to 5 mg/day. The proteinuria disappeared. During both pregnancies (the first beginning in December 1988 and the second in May 1992), the patient was placed on a prednisolone maintenance dose (5 mg/day). Both neonates were born healthy at term with no complications. Continuing prednisolone may be useful in pregnant women, and aggressive treatment to prevent mixed connective tissue disease exacerbation may be appropriate during pregnancy.     

Good response of membranous lupus nephritis to tacrolimus

A 22-year-old woman hospitalized for polyarthralgia was diagnosed with systemic lupus erythematosus (SLE). She was treated with prednisolone, and her clinical manifestations improved. However, she was re-admitted for renal biopsy because of persistent hypocomplementemia and development of proteinuria. The biopsy revealed segmental spike formation of basement membrane and subepithelial immune complex deposition, and membranous lupus nephritis (class V) was diagnosed. When tacrolimus was added to prednisolone, the serum complement titer quickly improved and proteinuria disappeared after about 11 months. Nevertheless, when tacrolimus was replaced examination showed cyclosporine due to gastrointestinal symptoms, she complained about arthralgia. Examination showed drop in the serum complement titer and recurrence of proteinuria. Renal biopsy at the time of recurrence showed increased subepithelial immune complex deposition in the capillary loops as compared to the first biopsy, a high degree of thickening of the basement membrane, and segmental circumferential interposition in some of the glomeruli. Membranous lupus nephritis (classes V + III) was diagnosed. By changing to tacrolimus and higher doses of steroids, the serum complement titer improved and proteinuria disappeared. This case indicates that tacrolimus can be an effective therapeutic agent for membranous lupus nephritis.     

Sequential Liver,Kidney, and Autologous Stem Cell Transplant for AL Amyloidosis: A Case Report

AL type amyloidosis is a systemic disease characterized by the accumulation of amyloid fibrils that can affect many organs such as the skin, gastrointestinal tract, heart, lungs, liver, and kidney. The most frequently involved organ in amyloidosis is the kidney, but cardiac amyloidosis with the poor prognosis is amyloid organ involvement. In this study, we present the treatment of a 40-year-old female patient with acute Budd-Chiari syndrome and very severe proteinuria with sequential liver, kidney, and autologous stem cell transplant after the diagnosis of systemic amyloidosis. To reduce the effects of massive proteinuria and very severe hypoalbuminemia, bilateral renal artery embolization was performed first. After the evaluation of the patient, she underwent liver transplant from a deceased donor, and then kidney transplant was performed from her son 1 month later. Afterward, the patient was discharged without any problems and underwent chemotherapy and stem cell transplant for primary AL amyloidosis. She was followed up without any problem in terms of liver, kidney, and stem cell at the 24th postoperative month. This case shows that autologous stem cell transplant after kidney and liver transplant may be a good treatment option in a selected patient with stem cell involvement diagnosed as having AL amyloidosis.     

Successful treatment of lipoprotein glomerulopathy in a daughter and a mother using niceritrol

We report two patients, a daughter and a mother, with lipoprotein glomerulopathy (LPG) who were successfully treated with niceritrol. Both patients carried a mutation in the apolipoprotein E (apoE) gene known as ApoE Tokyo/Maebashi. The daughter was found to have proteinuria at the age of 4 years. Four years later, she was diagnosed as having LPG based on a renal biopsy. She was treated with several medications including pravastatin, ethyl icosapentate, enalapril, warfarin and cyclophosphamide, all of which failed to reduce her proteinuria. At the age of 17 years, she exhibited an increase in proteinuria and a decline in renal function, despite ongoing treatment with pravastatin and enalapril. After switching from pravastatin to niceritrol, a marked reduction in the proteinuria and an improvement in renal function were observed. Her mother was found to have proteinuria at the age of 57 years and was diagnosed as having LPG based on a renal biopsy. She was also treated with niceritrol, resulting in an improvement in her proteinuria and renal function. These cases suggest that niceritrol might be a useful therapeutic option for LPG.     

Complete reversal of nephrotic syndrome secondary to amyloidosis with use of infliximab in a patient with inflammatory bowel disease and ankylosing spondylitis

A 30-year-old woman was diagnosed with ulcerative colitis in January 2006. One year later, she presented because of severe back pain and was diagnosed with ankylosing spondylitis (AS). In February 2008, the patient, while still under standard treatment for ulcerative colitis and AS, was admitted because of massive proteinuria and related symptoms. Nephrotic syndrome was observed and renal biopsy revealed amyloid deposits. After treatment with infliximab, nephrotic syndrome disappeared. We aim to present a case of secondary amyloidosis complicating ulcerative colitis and associated spondyloarthropathy.     

Breast cancer associated with pregnancy

Two cases of breast cancer associated with pregnancy were reported and the immunological assessment was performed in the second case. Case 1: A 36 year-old woman in the first trimester of pregnancy and having a large axillary mass and breast lump was admitted. She was diagnosed as having Stage IIIb breast cancer. After interruption of pregnancy, she received an extended radical mastectomy and radiotherapy. However, she died nine months after surgery for brain and liver metastases. Case 2: A 30 year-old woman in her second trimester of pregnancy was admitted for a large breast mass. She was diagnosed as having Stage IIIa breast cancer. Interruption of pregnancy was again necessary to perform surgery followed by chemotherapy. After an extended radical mastectomy she was placed on a combination chemotherapy regimen with cyclophosphamide, adriamycin and 5-FU. In both cases tumors began to develop rapidly at pregnancy. Immunological studies in Case 2 showed a depression of T-lymphocyte function and NK cell activity. Our study suggests that the depression of cell-mediated immunity during pregnancy may promote tumor growth.     

A case of de novo glomerulonephritis with electron-dense deposits following renal transplantation

Abstract:  We present here a case of de novo glomerulonephritis (GN) two yr after kidney transplantation. The patient was a 13-yr-old girl who had renal insufficiency because of bilateral hypoplastic kidneys. She received a renal allograft from her father at the age of 11 yr. Immunosuppressive treatment was started with tacrolimus, mizoribine (MZB), basiliximab, and methylprednisolone (mPSL). There were no findings of GN at the one-h biopsy (first biopsy). Two yr after transplantation, she showed proteinuria, hematuria and increased serum creatinine level with no apparent trigger. The biopsy specimen (fourth) showed mesangial proliferative GN with electron-dense deposits in a variety of regions and borderline changes indicating acute rejection. She was treated with mPSL pulse therapy, deoxyspergualin, replacement of MZB with mycophenolate mofetil, an increase of the mPSL dose, and candesartan. Her serum creatinine and urinary protein excretion levels improved after the treatment. One month later, she developed deterioration in her renal function again. Renal biopsy findings (fifth) were almost the same as the lesions observed in the fourth allograft biopsy. After she recovered from these episodes, she appeared to improve in clinical findings of GN. Protocol biopsies at three yr and five months after transplantation (sixth) showed no evidence of acute rejection, but we still observed the features of de novo GN. We could not resolve the underlying causes by reference to the clinical history and serological findings. We speculate that some kind of immunological reactions might be associated with the pathophysiology.     

Focal segmental glomerulosclerosis in a patient with polycythemia vera

Herein we describe the case of a patient with focal segmental glomerulosclerosis (FSGS) following polycythemia vera (PV) on whom hemodialysis was started 7 years later. A 66-year-old woman who had been treated for PV with hydroxyurea and phlebotomy for three years was referred to our hospital because of nephrotic syndrome. Renal biopsy performed at her local hospital revealed FSGS. Although she had received prednisolone at an initial dose of 45 mg/day, no significant improvement of proteinuria was achieved. The dose of prednisolone was tapered because the second renal biopsy revealed sclerosing glomerulopathy. We considered that FSGS was associated with PV because renal hemodynamic alterations in PV could result in FSGS as in any other secondary FSGS and there was no proteinuria at the initial detection of PV. On January 29, 1999, she developed massive proteinuria (9.6 g/day) and the findings of the third renal biopsy worsened in comparison with that of the first renal biopsy. Thereafter, hydroxyurea or ranimustine was used in treating PV at an outpatient clinic. However severe thrombocytosis was difficult to control, and progressive renal dysfunction finally necessitated hemodialysis on January 18, 2005. In conclusion, physicians should be aware of the risk of progressive renal failure in patients with FSGS following PV, particularly in patients with persistent thrombocytosis.     

A case of childhood IgA nephropathy who developed rapidly progressive glomerulonephritis in one-year clinical course

A 10-year-old girl who presented with microscopic hematuria, proteinuria and normal renal function has been followed up for the past two years. At the first examination, renal biopsy revealed focal/segmental lesions accompanying by occaisional necrosis and small crescents. Diagnosis of IgA nephropathy was given by light, electron and immunofluorescent microscopic findings. She started on the treatment with dipyridamol and was followed up for one year without any serious complications. Thereafter, she suddenly developed severe deterioration of renal function (serum creatinine 2.7 mg/dl) with nephrotic syndrome and hypertension. The second renal biopsy done at this time indicated the presence of typical crescentic glomerulonephritis with mesangial proliferation. No vasculitis was noted. She was intensively treated with steroids, anticoagulants and other medication and responded fairly well clinically. The third renal biopsy performed 5 months afterwards demonstrated marked histological improvement, but there was still present mesangial proliferation and varied degrees of sclerotic changes with fibrocellular crescents. Focal interstitial fibrosis and collapsed tubules were also seen. At present, 5 months after the last renal biopsy, she has improved much better and her serum creatinine decreased to 1.9 mg/dl, although proteinuria of 3 g/day still persists. It is suggested that only a small segmental necrosis with crescent formation in IgA nephropathy should be considered as an important indicator of disease activity in the evaluation of prognosis.     

Myocardial infarction in the third trimester of pregnancy

A 30-year-old woman developed severe chest pain while out shopping and was admitted to the delivery suite. She was 38 weeks pregnant with her second child. A diagnosis of myocardial infarction was made and cardiac arrest occurred shortly afterwards. She went into spontaneous labour 30 hours later and was delivered vaginally. This report reviews myocardial infarction in pregnancy and considers the clinical management of this patient.