Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice.

[primary hyperoxaluria type 1]

Primary hyperoxaluria type I (PH I ) is caused by deficiency of the liver -specific enzyme alanine-glyoxylate :aminotransferase (AGT ). Many mutations are known to perturb AGT protein folding . Vitamin B 6 (B 6 ) is the only specific drug available for treatment . Although B 6 has been used for >40 years , controlled data on B 6 efficacy are lacking . Therefore , this study investigated the absolute and relative change of urinary oxalate (Uox ) excretion under increasing dosages of B 6 , the first prospective trial to do so .B 6 response was studied in 12 patients (7 male patients ) with genetically confirmed PH I (3 Gly 170 Arg homozygous , 5 compound Gly 170 Arg and /or Phe 152 I le heterozygous , and 4 negative for Gly 170 A rg and /or Phe 152 I le mutations ) and noncompromised renal function . Efficacy was defined as a 30 % relative reduction in Uox excretion . B 6 was administered orally starting at 5 mg /kg body weight per day and given in increments of 5 mg /kg every 6 weeks , up to a final dosage of 20 mg /kg per day at week 24 . Uox and serum B 6 levels were measured every 6 weeks .Mean relative Uox reduction was 25 .5 %. Uox declined from 2 .09 Â±0 .55 (mean Â±SD ) at baseline to 1 .52 Â±0 .60 mmol /1 .73 m (2 ) per day (P =0 .01 ) at week 24 . Serum B 6 levels increased from 22 .5 Â±8 .7 to 1217 Â±776 ng /ml (P <0 .001 ). Six patients showed a â‰¥30 % relative reduction of Uox at week 24 .This first prospective trial confirmed B 6 efficacy in 50 % of patients (three of three homozygous , one of five heterozygous , and two of four patients negative for the Gly 170 A rg and /or Phe 152 I le mutations ). Interestingly , no complete biochemical remission was observed , even in the homozygous Gly 170 Arg study participants . Future trials are necessary to learn more about genotype-related B 6 response and B 6 metabolism .

Diseases
Validation

Diseases presenting "deficiency of the liver-specific enzyme" symptom

primary hyperoxaluria type 1

You can validate or delete this automatically detected symptom