|Year : 2007 | Volume
| Issue : 4 | Page : 174-175
Hereditary spherocytosis with nephrotic syndrome
A Mathew, J Varghese, G Kurian, VN Unni
Department of Nephrology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
V N Unni
Department of Nephrology, Amrita Institute of Medical Sciences and Research, Elamakkara P.O., Cochin - 682 026
Source of Support: None, Conflict of Interest: None
Hereditary spherocytosis is an autosomal dominant familial hemolytic disorder due to the abnormality of the erythrocyte membrane. We report a case of nephrotic syndrome due to membranoproliferative glomerulonephritis in a patient with hereditary spherocytosis.
Keywords: Hereditary spherocytosis, membranoproliferative glomerulonephritis
|How to cite this article:|
Mathew A, Varghese J, Kurian G, Unni V N. Hereditary spherocytosis with nephrotic syndrome. Indian J Nephrol 2007;17:174-5
| Introduction|| |
Hereditary spherocytosis, which is the commonest hereditary hemolytic anemia in Europe,  is not a very common disorder in our country. The hemolysis is due to an erythrocyte membrane defect resulting from deficiency or defects of one or more of the four membrane anchoring proteins in the RBCs. The association of hereditary spherocytosis with primary glomerular diseases such as minimal change disease (MCD) and Focal glomerulosclerosis has been reported in the literature. , Membranoproliferative glomerulonephritis is known to have a clinical association with sickle cell disease. The clinical association of membranoproliferative glomerulonephritis (MPGN) with hereditary spherocytosis is not described.
| Case Report|| |
A 34-year-old lady presented to us with pedal edema of 3 months duration. She was hypertensive since one year, but had no history of renal disease in the past. There was no history of urinary tract infection (UTI), renal calculus disease or any drug intake. She had a history of recurrent jaundice in the past, which was evaluated, and a diagnosis of hereditary spherocytosis with hemolytic jaundice was made. She underwent splenectomy 3 years back and did not have any episodes of jaundice subsequently. She was born of a nonconsanguineous marriage. The evaluation of her mother revealed spherocytosis with anemia and increased osmotic fragility of RBCs. Her sister also had spherocytosis and had undergone splenectomy for the same.
Clinical examination revealed pallor and bilateral pitting pedal edema. The blood pressure was 230/150 mm Hg; jugular veins were engorged and there were bilateral basal crepitations. Systemic examination did not reveal any other abnormality; there was no evidence of any systemic infection.
The hemoglobin level was 9 gm/dL; peripheral smear revealed characteristic microspherocytes along with acanthocytes and a few polychromatophilic RBCs.
The osmotic fragility was increased; there was autohemolysis when incubated at 37°C (mean corpuscular volume (MCV): 74.2 fL, mean corpuscular hemoglobin concentration (MCHC): 33.9 g/dL). Urine examination revealed 10-12 RBCs/HPF with a 24-h protein excretion of 5.29 g. Serum creatinine was 3 mg/dL; serum calcium, 7.4 mg/dL; serum phosphorus, 5.7 mg/dL; and serum albumin 3.3 gm/dL. Serum bilirubin, LDH and hepatic transaminases were normal, Serum complements (C3: 125 mg/dL, C4: 20.4) were normal. The Serology for HIV 1 and 2, HCV and HBsAg were negative. X-ray chest and hemoglobin electrophoresis were normal. ANA, Anti-dsDNA, Coomb's test, rheumatoid factor and cryoglobulins were negative.
USG abdomen revealed normal-sized kidneys with increased echotexture, but the corticomedullary differentiation maintained. Liver, GB, pancreas were normal. Spleen was not visualized, reflecting the postsplenectomy status. A percutaneous renal biopsy was performed, which revealed glomerular capillary wall thickening and hypercellular glomeruli with lobular accentuation [Figure - 1]; silver methenamine stain revealed doubling of the glomerular capillary basement membrane. IF showed peripheral capillary wall granular positivity (+++) for C3 and IgG (++).
| Discussion|| |
Since its first clinical description by Vanlair and Mesius in 1871,  hereditary spherocytosis has been recognized to be a familial hemolytic disorder with an autosomal dominant inheritance. Incomplete penetration and new mutations have been observed in some families.  The incidence has been reported to be 1:1000 to 1:4500 in the western literature,  although it is believed to be quite rare in India. The typical presentation in patients would be intermittent jaundice and splenomegaly. Some patients may have a mild disease, and the hemoglobin may be normal. The diagnostic features are the presence of characteristic microspherocytes (red cells are uniform, 6-7 microns in size, thicker than normal and show intense staining with lack of central pallor), increased osmotic fragility when the red blood cells are exposed to solutions of varying osmolalities, increased autohemolysis on the incubation of red cells at 37°C (corrected by the addition of glucose). The MCV is slightly reduced in general, and the MCHC is increased. Spheroidicity may be quantitatively assessed by the measurement of the osmotic fragility of the RBC on exposure to hyposmotic solutions causing a net influx of water. ,
Hemolysis in this disorder is due to an intrinsic red-cell abnormality in the presence of an intact spleen, where it occurs. A molecular defect in one of the proteins in the cytoskeleton of the RBC membrane leads to a loss of membrane and hence decreased ratio of surface area to volume and consequently spherocytosis. The molecular abnormality in hereditary spherocytosis primarily involves the protein responsible for tethering the lipid bilayer to the underlying cytoskeletal network. The four membrane-anchoring proteins have been identified as Ankyrin, Protein 3, Spectrin and Palladin.  Approximately 50% have a defect in Ankyrin, around 25% have a defect in the protein 3 and the most of the remaining 25% exhibit mutations in Spectrin. The deficiency of palladin is a less common cause for hereditary spherocytosis. 
The survival of these red cells is reduced when infused into normal subjects; normal red cells infused into patients with hereditary spherocytosis have normal survival. Splenectomy is the treatment of choice; this improves the survival of red cells considerably.
Spinal cord demyelination has been reported in patients with hereditary spherocytosis, and it has been postulated that the proteins of the red-cell membrane may have immunological cross-reactive structural or functional analogues in the dendrites of the neurons,  Focal segmental sclerosis and MCD have been reported in patients with hereditary spherocytosis. ,,, The exact mechanism of the association is unknown; however, an immunological cross reaction between the red-cell membrane proteins and glomerular capillary membrane proteins may be a reasonable hypothesis. It is also possible that the alteration in intracellular or cell-membrane-associated proteins in the renal glomerular cells may interfere with the normal function, thereby resulting in proteinuria and progressive renal failure. Our patient with hereditary spherocytosis developed membranoproliferative glomerulonephritis, and this association is not mentioned in the literature. It is quite possible that this may be a coincidence.
| References|| |
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[Figure - 1]