Hypophosphatasia: Nonlethal disease despite skeletal presentation in utero (17 new cases and literature review)
- 28 June 2011
- journal article
- review article
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 26 (10), 2389-2398
- https://doi.org/10.1002/jbmr.454
Abstract
Hypophosphatasia (HPP) is caused by deactivating mutation(s) within the gene that encodes the tissue‐nonspecific isoenzyme of alkaline phosphatase (TNSALP). Patients manifest rickets or osteomalacia and dental disease ranging from absence of skeletal mineralization in utero to only loss of adult dentition. Until recently, HPP skeletal disease in utero was thought to always predict a lethal outcome. However, several reports beginning in 1999 emphasized a benign prenatal form of HPP (BP‐HPP) where skeletal disease detected in utero had a mild postnatal course. Here we describe prenatal and postnatal findings of 17 additional BP‐HPP patients among our 178 pediatric HPP patients. Their findings are compared with those of their siblings with HPP, carrier parents, and others with identical TNSALP mutations. New information concerning 7 previously published BP‐HPP patients accompanies a review of the HPP literature. Among our 17 BP‐HPP patients, prenatal ultrasound showed normal chest or abdominal circumferences where recorded. Sometimes, poor skeletal mineralization, fetal crowding, and third‐trimester improvement were observed. Postnatally, extremity bowing further improved (13 patients). BP‐HPP severity postnatally spanned the “infantile” to “odonto” HPP phenotypes, resembling our patients who harbored identical TNSALP mutation(s). Eight had autosomal dominant (AD) and 9 had autosomal recessive (AR) BP‐HPP. Fourteen of our 15 mothers were HPP carriers or affected. Of the 41 cumulative BP‐HPP patients (24 literature cases meriting a BP‐HPP diagnosis since 1996 plus our 17 patients), 63% had AR BP‐HPP. Maternally transmitted HPP involved 11 of the 13 total AD BP‐HPP probands (p = 0.01), supporting a maternal in utero effect on the baby. Fetal crowding, normal fetal mineralization and chest size, and TNSALP heterozygosity seem to identify BP‐HPP. However, bowed fetal long bones with AR HPP, specific TNSALP mutations, or poor skeletal mineralization before the third trimester do not reliably diagnose HPP lethality. © 2011 American Society for Bone and Mineral ResearchKeywords
This publication has 52 references indexed in Scilit:
- Autosomal Recessive Hypophosphatasia Manifestingin Uterowith Long Bone Deformity but Showing Spontaneous Postnatal ImprovementJournal of Clinical Endocrinology & Metabolism, 2008
- Reference values for clinical chemistry tests during normal pregnancyBJOG: An International Journal of Obstetrics and Gynaecology, 2008
- Specific osseous spurs in a lethal form of hypophosphatasia correlated with 3D prenatal ultrasonographic imagesPrenatal Diagnosis, 2007
- Homozygosity for TNSALP mutation 1348c>T (Arg433Cys) causes infantile hypophosphatasia manifesting transient disease correction and variably lethal outcome in a kindred of black ancestryThe Journal of Pediatrics, 2006
- Characterization of Missense Mutations and Large Deletions in theALPLGene by Sequencing and Quantitative Multiplex PCR of Short FragmentsGenetic Testing, 2006
- Common mutations F310L and T1559del in the tissue-nonspecific alkaline phosphatase gene are related to distinct phenotypes in Japanese patients with hypophosphatasiaEuropean Journal of Pediatrics, 2005
- Bilateral Transverse (Bowdler) Fibular Spurs with Hypophosphatasia in an Adolescent GirlKorean Journal of Radiology, 2005
- A molecular approach to dominance in hypophosphatasiaHuman Genetics, 2001
- Increased plasma pyridoxal‐5′‐phosphate levels before and after pyridoxine loading in carriers of perinatal/infantile hypophosphatasiaJournal of Inherited Metabolic Disease, 1989
- HypophosphatasiaPediatric Radiology, 1976