Fractures and Fanconi Syndrome due to Prolonged Sodium Valproate Use

Abstract

Background:

Sodium valproate (VPA) is commonly used to treat epilepsy in children. Renal dysfunction is a rare side effect but can present as tubulopathy such as Fanconi syndrome.

Case Report:

We report on an 8-year-old disabled girl with myoclonic epilepsy who was referred for investigation of recurrent low impact fractures of the distal femur which were initially thought to be caused by her severe immobility. However, she was subsequently found to have hypophosphataemia secondary to Fanconi syndrome due to prolonged VPA use. After VPA withdrawal renal function and serum phosphate levels normalised and X-rays improved dramatically.

Conclusion:

The possibility of drug-induced osteoporosis and fractures should always be considered in disabled children, even in the presence of severe immobility.

Key words

sodium valproate - Fanconi syndrome - hypophosphataemic rickets - fractures - immobility

• References

• 1 British National Formulary No 58. Sept 2009. BMJ Group and RPS Publishing.
• 2 Bergwitz C, Juppner H. Chapter 9. Disorders of Phosphate Homeostasis and Tissue Mineralisation. In: Allgrove J, Shaw NJ. (eds) Calcium and Bone Disorders in Children and Adolescents. Endocrine Development. Basel: Karger; 2009. 16. 133-156
• 3 Donadio C. Serum and urinary markers of early impairment of GFR in chronic kidney disease patients: diagnostic accuracy of urinary β-trace protein. Am J Physiol Renal Physiol 2010; 299: F1407-F1423
• 4 Endo A, Fujita Y, Fuchigami T et al. Fanconi syndrome caused by valproic acid. Pediatr Neurol 2010; 42: 287-290
• 5 Fakuda Y, Watanabe H, Ohtomo Y et al. Immunologically mediated chronic tubulo-interstitial nephritis caused by valproate therapy. Nephron 1996; 72: 328-329
• 6 Hawkins E, Brewer E. Renal toxicity induced by valproic acid. Pediatric Pathol 1993; 13: 863-868
• 7 Jaffe SL, Sanford M. Valproate-induced proximal renal tubular dysfunction: clinically relevant in the severely disabled epileptic population. Epilepsia 2005; 46: 599-600
• 8 Knorr M, Schaper J, Harjes M et al. Fanconi syndrome caused by antiepileptic therapy with valproic acid. Epilepsia 2004; 45: 868-871
• 9 Lande M, Kim M, Bartlett C et al. Reversible Fanconi syndrome associated with valproate therapy. J Pediatr 1993; 123: 320-322
• 10 Lenoir G, Perignon J, Gubler MC et al. Valproic acid: a possible cause of proximal tubular renal syndrome. J Pediatr 1981; 98: 503-504
• 11 Magen D, Berger L, Coady MJ et al. A loss-of-function mutation in NaPi-IIa and renal Fanconi’s syndrome. N Engl J Med 2010; 362: 1102-1109
• 12 Nicolaidou P, Georgouli H, Kotsalis H et al. Effects of anticonvulsant therapy on vitamin D status in children: prospective monitoring study. J Child Neurol 2006; 21: 205-210
• 13 Rauchenzauner M, Griesmacher A, Tatarczyk T et al. Chronic antiepileptic monotherapy, bone metabolism, and body composition in non-institutionalized children. Dev Med Child Neurol 2010; 52: 283-288
• 14 Sirac C, Bridoux F, Essig M et al. Toward Understanding renal Fanconi syndrome: step by step advances through experimental models. Contrib Nephrol 2011; 169: 247-261
• 15 Smith G, Balfe J, Kooh S. Anticonvulsants as a cause of Fanconi syndrome. Nephrol Dial Transplant 1995; 10: 543-545
• 16 Watanabe T, Yoshikawa H, Yamazaki S et al. Secondary renal Fanconi syndrome caused by sodium valproate therapy. Pediatric Nephrol 2005; 20: 814-817
• 17 Yoshikawa H, Wantanabe T, Abe T. Tubulo-interstitial nephritis casued by sodium valproate. Brain and Development 2002; 24: 102-105
• 18 Zaki El, Springate JE. Renal injury from valproic acid: A case report and literature review. Paediatric Neurol 2002; 27: 318-319