Case 57: Additional Diagnostic Testing [Pediatrics] -

Here are some more diagnostic tests…

Urine studies:

Additional serum studies:

C3 – 49 mg/dL (61-162 mg/dL)
C4 – 12 mg/dL (8-34 mg/dL)
ADAMST13 – 71 % (>= 40%)
Fibrinogen – 119 mg/dL (170-410 mg/dL)
D-Dimer – 1.60 ug/mL (<0.50 ug/mL)
Urine P:C Ratio – 0.48 mg/mg (0.08-0.28 mg/mg)
Urine A:C Ratio – 0.56 mg/mg (<0.030 mg/mg)
Negative infectious work-up from blood, stool, urine, and CSF

Of the following next steps, select the 3 most helpful tests to assist in your evaluation:

Abdominal ultrasound with Doppler

Great choice! This is a helpful, noninvasive test to evaluate the abdominal organs and kidneys for structural or flow abnormalities that may explain his presentation

Scrotal ultrasound with Doppler

Explanation: While he has scrotal swelling, it is unlikely that there is pathology in the scrotum contributing to his presentation. This would be of low yield. Try again!

Babygram

Radiographs are often not helpful in diagnosing renal pathology, unless looking for bone disease or stones. Pick again!

Peripheral blood smear

Yes! This test will be helpful to rule out a TMA. He has multiple abnormal RBC morphologies on his CBC consistent with a microangiopathic hemolytic process occurring, in addition to his anemia, thrombocytopenia, and AKI.

A kidney biopsy was deferred due to the critical illness of this neonate. Genetic testing is performed. Based on this patient’s presentation, what is the most likely mutation in the genetic testing?

CF1 (Complement Factor 1)

Correct! In this patient with evidence of thrombotic microangiopathy (TMA), genetic testing should look for potential abnormalities of the complement pathway. Atypical hemolytic uremic syndrome functional panel tests typically include several biomarkers (C3, C3c, C4, FB, Ba, Bb, FD, Properdin, C5, soluble C5b-9, FH, FI), autoantibody tests (FHAA, FBAA), and functional tests (CH50, AP Functional Assay, C3b Deposition Assay, Fluid Phase Activity Assay by IFE) that assess activity of the complement pathways. Our patient’s genetic testing revealed a mutation of CF1 of unknown clinical significance, and functional studies revealed reduced activity of the AP50 enzyme – suggesting a deficiency in Factor D, H, or Properdin.