Vitamin B6 deficiency with normal plasma levels of pyridoxal 5'-phosphate in perinatal hypophosphatasia.

Abstract

Pyridoxal 5'-phosphate (PLP), the principal circulating form of vitamin B6 (B6), is elevated in the plasma of individuals with hypophosphatasia (HPP). HPP is the inborn-error-of-metabolism caused by loss-of-function mutation(s) of ALPL, the gene that encodes the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP). PLP accumulates extracellularly in HPP because it is a natural substrate of this cell-surface phosphomonoester phosphohydrolase. Even individuals mildly affected by HPP manifest this biochemical hallmark, which is used for diagnosis. Herein, an exclusively breast-fed newborn boy with life-threatening perinatal HPP had uniquely normal instead of markedly elevated plasma PLP levels before beginning asfotase alfa (AA) TNSALP-replacement therapy. These abnormal PLP levels were explained by B6 deficiency, confirmed by his low plasma level of 4-pyridoxic acid (PA), the B6 degradation product. His mother, a presumed carrier of one of his two ALPL missense mutations, had serum ALP activity of 50U/L (Nl 40-130) while her plasma PLP level was 9 μg/L (Nl 5-50) and PA was 3 μg/L (Nl 3-30). Her dietary history and breast milk pyridoxal (PL) level indicated she too was B6 deficient. With B6 supplementation using a breast milk fortifier, the patient's plasma PA level corrected, while his PLP level remained in the normal range but now in keeping with AA treatment. Our experience reveals that elevated levels of PLP in the circulation in HPP require some degree of B6 sufficiency, and that anticipated increases in HPP can be negated by hypovitaminosis B6.