Infant with gross hematuria and nephrotic syndrome: answers

Our differential diagnosis was acute glomerulonephritis due to infections known to cause nephrotic syndrome (NS) in the first year of life, including syphilis, toxoplasmosis, cytomegalovirus (CMV), rubella, hepatitis B, hepatitis C, human immunodeficiency virus (HIV), parvovirus, Epstein-Barr virus (EBV), herpes simplex virus (HSV), hemolytic–uremic syndrome (HUS), autoimmune disease [systemic lupus erythematosus (SLE), vasculitis], malignancy, and primary (genetic) NS with later presentation at 9 months of age (Table 1). Due to severe gross hematuria, NS and decreased renal function on admission, percutaneous renal biopsy was performed on hospital day 1 without complications. Renal ultrasonography with Doppler flow showed no evidence of renal vein thrombosis. Histologic laboratory tests showed complement levels C3 and C4 were within normal limits [120 (85–157) and 27 (15–38) mg/dl respectively], as well as total complement CH50 46 (40–70). All tests for infectious causes were negative, including antibodies to HSV, Rubella, toxoplasmosis, EBV, hepatitis C, HIV, parvovirus; polymerase chain reaction (PCR) for EBV and parvovirus; hepatitis B antigen; rapid plasma reagin test for syphilis; and nasopharyngeal viral culture including adenovirus, influenza A and B, parainfluenza, meta-pneumovirus, and respiratory syncytial virus. Stool culture for Escherichia coli O157 was negative. Serologic tests to look for SLE (antinuclear antibodies, antibodies to double-stranded DNA) and vasculitis (antineutrophil cytoplasmic antibodies) were also negative. A peripheral blood smear was done to evaluate for HUS and malignancy. The smear showed normocytic anemia without red blood cell morphologic abnormalities and no evidence of microangiopathic hemolysis. For possibility of Denys-Drash syndrome (DDS) in an infant with female phenotype, karyotype was tested and showed normal 46 XX female. Genetic testing for gene mutations in PLCE1, LAMB2, WT1, NPHS1, and NPHS2 genes for early-onset NS showed DNA sequence variants in NPHS1 (heterozygous transition G>A, nucleotide position IVS9+8) and WT1 (heterozygous, transition T>C, nucleotide position 844, codon position 282, amino acid change cysteine>arginine), which were of unknown clinical significance and have not been associated with NS (Athena Diagnostics Inc., Worchester, MA, USA). This refers to the article that can be found at http://dx.doi.org/10.1007/ s00467-011-1965-z