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Bone Abstracts (2017) 6 P031 | DOI: 10.1530/boneabs.6.P031

ICCBH2017 Poster Presentations (1) (209 abstracts)

Valproic acid induces Fanconi syndrome and reversible hypophosphataemic rickets via upregulation of fibroblast growth factor 23

Vrinda Saraff 1 , Raja Padidela 2 , Talat Mushtaq 3 , Sophia Sakka 1 , Zulf Mughal 2 & Wolfgang Högler 1,

1Birmingham Children’s Hospital, Birmingham, UK; 2Royal Manchester Children’s Hospital, Manchester, UK; 3Leeds Children’s Hospital, Leeds, UK; 4University of Birmingham, Birmingham, UK.

Background: Valproic Acid (VPA) is a commonly used antiepileptic drug in the management of childhood epilepsy. Renal dysfunction presenting as Fanconi syndrome (FS) is a rare side effect of VPA use. This can lead to renal tubular phosphate loss, resulting in hypophosphataemic rickets, low bone mass and fractures. We report 6 children with VPA induced FS from three tertiary paediatric metabolic bone centres across England.

Presenting problem: P1: Global developmental delay of unknown cause, cortical blindness and sensory neural hearing loss

P2: Menkes disease

P3: Mowat-Wilson Syndrome

P4 and P6: Quadriplegic cerebral palsy secondary to hypoxic ischaemic encephalopathy

P5: Lissencephaly

All children were developmentally delayed, at least partially immobile and presented with low trauma fractures, all were gastrostomy fed and on VPA for epilepsy management (Table). The diagnosis of FS was established by confirming hypophosphatemia, phosphaturia and aminoaciduria. All had elevated alkaline phosphatase activity and normal 25 OHD levels, apart from P1 (29.2 nmol/l). X rays confirmed marked osteopenia.

Clinical management: Proximal tubular dysfunction and serum phosphate normalised within 6–12 months of stopping VPA. Marked radiological improvement was noted in P1, P3 and P4, however P2 and 5 received intravenous Zoledronic acid infusions due to further long bone fractures. In one patient (P5), post VPA weaning, Fibroblast growth factor 23 (FGF23) normalised to 63 RU/ml (0–99).

Discussion: The exact mechanism of VPA induced FS is not clearly understood. Elevated FGF23 levels in three patients suggest VPA mediated dysregulation, leading to worsening renal phosphate loss and resulting in osteopenia (osteomalacia). In addition, immobility in this severely disabled subgroup of children on VPA, contributes to poor bone health.

Table Clinical and biochemical characteristics at presentation
Age in years, Gender8, F5, M6, M6, F9, M6, M
Duration on VPA 7y4.5y4.8y5y7.5y3.5y
Long bone fractures131331
Serum phosphate (1.0–1.8 mmol/l)0.290.810.380.340.370.74
Serum alkaline phosphatase U/L2219117033751197934615
PTH ng/l (10–60)12216.712.15452
25OHD (>50 nmol/l)29.21391181176982.9
TmP GFR (1.14–2.44)
FGF23 (0–99 RU/ml)195219136
VPA, Valproic acid; TmP GFR, renal tubular maximum reabsorption of phosphate per litre of glomerular filtration rate; FGF23, Fibroblast growth factor 23.

Disclosure: The authors declared no competing interests

Volume 6

8th International Conference on Children's Bone Health


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