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Progressive renal insufficiency in methylmalonic acidemia
K H Molteni1, T D Oberley, J A Wolff
1Department of Pediatrics, University of Wisconsin School of Medicine, Madison 53792.
Abstract:
Methylmalonic acidemia is a heterogeneous inborn error of propionate metabolism. Therapy frequently includes a low-protein diet to minimize precursors of methylmalonic acid (MMA) and reduce its concentration in body tissues. Renal dysfunction in these patients is increasingly recognized. Tubulointerstitial disease has been found in the small number of renal biopsy specimens from young children previously reported by others. We describe an 18-year-old patient with the mut- form of the disease who developed renal dysfunction despite the use of a low-protein diet. Tubulointerstitial injury was documented by renal biopsy. The patient had no risk factors associated with established causes of chronic tubulointerstitial nephropathy (CTIN). We postulate that methylmalonyl-CoA and/or its precursors (propionyl-CoA, odd-chain fatty acids), may be capable of producing CTIN. We speculate that prevention of renal injury may require lower tissue levels of MMA and its precursors than those required for prevention of ketoacidosis.
Insights
Methylmalonic acidemia can cause kidney damage even with a low-protein diet. This study suggests lower metabolite levels may be needed to prevent chronic tubulointerstitial nephropathy (CTIN) in patients.
Area of Science:
- Biochemistry
- Nephrology
- Metabolic Disorders
Background:
- Methylmalonic acidemia (MMA) is an inborn error of propionate metabolism.
- Treatment involves a low-protein diet to reduce methylmalonic acid (MMA) levels.
- Renal dysfunction is a recognized complication, with tubulointerstitial disease noted in prior studies.
Observation:
- An 18-year-old patient with mut- form methylmalonic acidemia developed renal dysfunction despite dietary management.
- Renal biopsy confirmed tubulointerstitial injury.
- The patient lacked risk factors for typical chronic tubulointerstitial nephropathy (CTIN).
Findings:
- Methylmalonyl-CoA and its precursors (propionyl-CoA, odd-chain fatty acids) are implicated in causing CTIN.
- This suggests a direct nephrotoxic effect of these metabolites.
Implications:
- Preventing renal injury in methylmalonic acidemia may necessitate stricter metabolite control than previously thought.
- Lowering tissue levels of MMA and its precursors might be crucial for renal health.
- This highlights the importance of monitoring kidney function in these patients.