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Atypical glomerulopathy associated with the cblE inborn error of vitamin B₁₂ metabolism
Erin A Paul1, Marta Guttenberg, Paige Kaplan
1Department of Pediatrics, Columbia Medical Center, 630 W 168th St, New York, NY 10032, USA.
Insights
The cblE disorder, a vitamin B12 metabolism defect, can cause atypical glomerulopathy. This case highlights kidney complications previously unobserved in cblE disease patients.
Area of Science:
- Biochemistry
- Genetics
- Nephrology
Background:
- The cblE disorder is an inherited vitamin B12 metabolism defect causing elevated homocysteine and decreased methionine.
- Renal complications are known in cblC disease but not previously reported in cblE disease.
Observation:
- A patient with cblE disease presented with atypical glomerulopathy, proteinuria, and progressive renal insufficiency.
- Fibroblast studies showed decreased methyltetrahydrofolate incorporation and methylcobalamin synthesis.
- Renal biopsy revealed histological and ultrastructural findings similar to, but not identical to, idiopathic membranoproliferative glomerulonephritis (MPGN) and thrombotic microangiopathy (TMA).
Findings:
- Complementation analysis confirmed the patient's condition as cblE disease.
- The patient exhibited an atypical glomerulopathy resembling MPGN.
- Additional clinical features included migraine headaches, hypothyroidism, and livedo reticularis.
Implications:
- This study expands the known clinical spectrum of cblE disease to include renal complications.
- It suggests a potential link between vitamin B12 metabolism defects and glomerular diseases.
- Further research is warranted to understand the pathogenesis of renal involvement in cblE disorder.
Background:
The cblE disorder is an inherited disorder of vitamin B12 metabolism that results in elevated levels of homocysteine and decreased methionine in body fluids. Renal complications have been reported in patients with cblC disease, but not in those with cblE disease. The renal complications of cblC disease include thrombotic microangiopathy (TMA), neonatal hemolytic uremic syndrome, chronic renal failure, tubulointerstitial nephritis and proximal renal tubular acidosis. Previously, we reported a patient with cblC disease who had an atypical glomerulopathy that manifested with proteinuria and progressive renal insufficiency.
Case-Diagnosis/Treatment:
Studies were done on cultured fibroblasts. Renal biopsy tissue was examined by light and electron microscopy. There was decreased incorporation of labeled methyltetrahydrofolate and decreased synthesis of methylcobalamin. Complementation analysis placed the patient into the cblE complementation group. The findings from the histological and ultrastructural studies of renal biopsy were similar, but not identical, to those of idiopathic membranoproliferative glomerulonephritis (MPGN) and overlapped with those of TMA.
Conclusions:
We describe a patient with cblE disease who had an atypical glomerulopathy similar to MPGN. Additional findings included migraine headaches, hypothyroidism and livedo reticularis.
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