Case Quiz (January 2020)
A 5-year-old boy with an 9-month-old history of undiagnosed lymphadenopathy and hepatosplenomegaly, presented to ER with abdominal distention and fever. Three weeks prior, he had experienced a purpuric rash, which resolved within 3 days, Rt. knee and Lt. elbow swellings. CBC showed anemia (Hb 8.1 g/dL), absolute neutrophil count (820/mm3) and normal platelets count. Other investigations revealed BUN 72mg/dl, creatinine 2.3 mg/dl, albumin 2.8 gm/dl, potassium 6.1 meq/l, sodium 143 meq/l, magnesium 1.2 mol/L and creatine phosphokinase was normal at 44 U/L. There was no clear evidence of a hemolytic anemia, with a normal haptoglobin of 92 mg/dl, normal LDH of 746 U/L, and no schistocytes on blood film.
Further investigations revealed elevated serum ferritin 223.5 μg/L, C3 and C4 were normal, high IgA at 2.9 g/L. ANA was positive at 1:160; anti-dsDNA, ANCA, and anti-GBM were all negative. Of note, his vitamin B12 levels in the serum were very elevated at > 4427 pmol/L (normal 218–1305 pmol/L).
On examination, the patient’s blood pressure was elevated at 135/85, and his respiratory rate (RR) was also increased at 46/minute. A chest x-ray showed mild bilateral pleural effusions. There was no rash or evidence of joint swelling at time of presentation. Ultrasound showed hepatosplenomegaly and enlarged lymph nodes at porta hepatis and para-aortic areas, bilateral normal-sized and grade II echogenic kidneys.
The patient had initial normal urinalysis. After couple of weeks, the patient developed mild proteinuria, with a protein/ creatinine ratio of 2.7 with drop of serum albumin to 2.2 g/L.
A renal biopsy was performed.
Case Answer (January 2020)
Autoimmune lymphoproliferative syndrome (ALPS). ALPS is an immune dysregulation syndrome caused by defective lymphocyte apoptosis. Common clinical features include lymphadenopathy, splenomegaly, and cytopenia. The diagnostic laboratory test is the presence of T cells. A high vitamin B12 level is also suggestive, as was seen in our patient. Two-thirds of patients have mutations in the FAS gene, which is a regulator of apoptosis.
Given the normal complements and negative dsDNA, ANCA, and anti-GBM, systemic lupus, or ANCA-mediated vasculitis process was unlikely. IgA was high, and given the microscopic hematuria and proteinuria, IgA vasculitis remained a possibility, although there were no episodes of gross hematuria.
With the high vitamin B12 levels and bicytopenia, the diagnosis of autoimmune lymphoproliferative syndrome (ALPS) was most likely. Given his hypertension, proteinuria, and hematuria with acute kidney injury, we felt she clinically had signs of glomerulonephritis (GN), most likely secondary to ALPS.
