Chronic interstitial nephritis: a long-term complication of methylmalonic acid(MMA)-emia

Abstract

In a girl with a Cbl A mutant of MMA-emia treated since the neonatal period with a low protein diet, MMA conc. in urine (mol/mol creat.) varied from 0.9-3.5 (x=2.2) rising to max. 6.4 during infections. MMA plasma conc. (mmol/l) ranged from 0-1-0.4, occasionally up to 1-3. The patient was only partially B₁₂-responsive. The only two episodes of metabolic acidosis could easily be controlled. Physical and psychomotor development (IQ 100) was normal until 12 yrs of age when growth retardation was noted. Laboratory studies revealed hyperuricemia (560-780 μmol/l), low urinary uric acid and impaired creatinine clearance: 45 ml/min /1.73 m². Hyperuricemia was normalized by allopurinol. By further restriction of protein intake (0.5 g/kg/d), oral OH-Cbl, I-carnitine and alkali MMA levels could be reduced to x=1.5 mol/mol creat, and there was catch-up growth. At age 17 yrs the girl was in good general health. Her renal function was: C_inulin: 54 ml/min/1,73m², C_PAH: 270 ml/min/1.73 m². Fractional excretion of sodium was increased to 5%. Blood pressure was elevated (145/100 mmHg). The renal biopsy showed a moderate focal interstitial nephritis with tubular atrophy, slight nephrosclerosis without glomerulonephritis, no urate deposits.

Conclusion: Chronic renal disease, not uncommon in patients with MMA-emia, may be caused by MMA itself or secondarily by hyperuricemia. In our case the renal function did not deteriorate over 5 years under a strict therapeutic regimen. MMA and urate levels must be carefully controlled in these patients. It remains to be shown whether the development of nephropathy can thus be prevented.

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