Abstract
We describe a patient diagnosed with lethal perinatal hypophosphatasia with a unique clinical presentation of convulsions that responded to vitamin B6. Genomic DNA sequence analysis of the tissue-nonspecific alkaline phosphatase (TNSALP) gene revealed two missense mutations: a G-to-A transition resulting in a Glu to Lys at codon 274 (E274K), and a G-to-C transversion resulting in a Gly to Arg at codon 309 (G309R). The first mutation was maternally transmitted and was previously characterized as a moderate one, whereas the latter was paternally transmitted and has not been previously reported. Phenotype/genotype correlation indicates that G309R is a deleterious mutation that can lead to seizures and a lethal outcome, as was demonstrated in our patient.
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Litmanovitz, I., Reish, O., Dolfin, T. et al. Glu274Lys/Gly309Arg Mutation of the Tissue-Nonspecific Alkaline Phosphatase Gene in Neonatal Hypophosphatasia Associated with Convulsions. J Inherit Metab Dis 25, 35–40 (2002). https://doi.org/10.1023/A:1015121414782
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DOI: https://doi.org/10.1023/A:1015121414782