Hypophosphatasia: Skeletal Presentation In Utero of Non-Lethal Disease
Journal of Bone and Mineral Research
American Society for Bone and Mineral Research
Hypophosphatasia (HPP), from deactivating mutation(s) within the “tissue nonspecific” alkaline phosphatase (TNSALP) gene, features rickets/osteomalacia and dental disease ranging from in utero absent skeletal mineralization to loss of adult dentition. Several reports characterize a “benign prenatal” phenotype (BP-HPP).
Seventeen of our 178 pediatric HPP patients have unreported BP-HPP. Here, we describe their prenatal and postnatal findings comparing them to affected siblings, carrier parents, and others with identical TNSALP mutations. New information concerning seven previously published BP-HPP pts is also included with an extensive literature review.
Among our 17 pts, eight autosomal dominant (AD) and nine autosomal recessive (AR) BP-HPP, prenatal ultrasounds had shown normal chest or abdominal circumferences, poor skeletal mineralization, fetal packing, and third trimester improvement. Postnatally, extremity bowing further improved (13 pts). BP-HPP severity spanned “infantile” to “odonto” HPP phenotypes, resembling our pts with identical TNSALP mutation(s). Fourteen of the 15 mothers were HPP carriers or affected. Of 41 cumulative BP-HPP pts (24 literature cases since 1996 meriting a BP-HPP diagnosis, plus our 17), most (26) had AR BP-HPP. Maternally transmitted HPP affected eleven of the 13 AD BP-HPP probands (p=0.01), including seven of our eight (p=0.035), supporting a maternal in utero effect.
Fetal packing, heterozygosity, and normal fetal mineralization and chest size seem to identify BP-HPP. However, bowed fetal long bones with AR HPP, specific TNSALP mutations, or poor skeletal mineralization before the third trimester (including in an abortus) do not reliable diagnose HPP lethality.
alkaline phosphatase, metabolic bone disease, rickets, prenatal diagnosis, skeletal dysplasia
D Wenkert, W H. McAlister, Stephen P. Coburn, J A. Zerega, L R. Ryan, Karen L. Ericson, J H. Hersh, S Mumm, and Michael P. Whyte (2011).
Hypophosphatasia: Skeletal Presentation In Utero of Non-Lethal Disease. Journal of Bone and Mineral Research.26 (10), 2389-2398. American Society for Bone and Mineral Research.