Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene

Vitamin B-6 Metabolism and Interactions with TNAP

“…This was confirmed in knockout mice lacking TNAP which died from seizures (Waymire et al 1995). Pyridoxal phosphate in cerebrospinal fluid was above the normal range in three infants with hypophosphatasia (Baumgartner-Sigl et al 2007;Hofmann et al 2013;Belachew et al 2013) supporting the hypothesis that low alkaline phosphatase activity restricted uptake of vitamin B-6 by the brain. Waymire et al (1995) hypothesized that the seizures resulted from decreased concentration of the inhibitory neurotransmitter, gamma-aminobutyrate (GABA).…”

“…Patients with vitamin B-6 related seizures tended to have lower cerebrospinal fluid values and higher plasma values yielding a plasma/cerebrospinal fluid ratio of 21. It is interesting to note that an infant with hypophosphatasia and pyridoxine responsive seizures had a ratio of 36 (Baumgartner-Sigl et al 2007) even though the concentration of pyridoxal phosphate in the spinal fluid was 57 nmol/L compared with their cited normal range of 7-39 nmol/L (Shin et al 1984). This suggests that the ratio may be a more reliable marker of potential seizures than the cerebrospinal fluid value alone.…”

“…This suggests that the ratio may be a more reliable marker of potential seizures than the cerebrospinal fluid value alone. Baumgartner-Sigl et al (2007) noted that all reported cases of hypophosphatasia with neonatal seizures died by 18 months of age. Di Mauro et al (2002) found that various TNAP mutations differed in their ability to hydrolyze pyridoxal phosphate.…”

“…Bethenod et al did administer pyridoxine but it was not effective in relieving the seizures. Since then there have been multiple reports in which vitamin B-6 supplementation was beneficial (Sia et al 1975;Litmanovitz et al 2002;Nunes et al 2002;Yamamoto et al 2004;Arun et al 2005;Baumgartner-Sigl et al 2007;Balasubramaniam et al 2010;Demirbilek et al 2012;Belachew et al 2013). Vitamin B-6 supplementation also corrected seizures in mice lacking alkaline phosphatase (Waymire et al 1995;Narisawa et al 2001).…”

Outcome of Perinatal Hypophosphatasia in Manitoba Mennonites: A Retrospective Cohort Analysis

“…Seizures may occur and are typically due to pyridoxine deficiency in the central nervous system ). When such seizures occur, the prognosis is grim: In a recent review of the literature, no patients with HPP and pyridoxineresponsive seizures survived beyond 18 months of age (Baumgartner-Sigl et al 2007). The outcome of infantile HPP is less certain.…”