Autosomal Recessive Hypophosphatasia Manifestingin Uterowith Long Bone Deformity but Showing Spontaneous Postnatal Improvement
Open Access
- 1 September 2008
- journal article
- case report
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 93 (9), 3443-3448
- https://doi.org/10.1210/jc.2008-0318
Abstract
Context: Hypophosphatasia (HPP) is a heritable metabolic disorder of the skeleton that includes variable expressivity conditioned by gene dosage effect and the variety of mutations in the tissue nonspecific alkaline phosphatase (TNSALP) gene. Patient age when skeletal problems first manifest generally predicts the clinical course, with perinatal HPP causing bone disease in utero with postnatal lethality. Objective: Our objective was to identify TNSALP mutations and characterize the inheritance pattern of a family with clinically variable HPP with one child manifesting in utero with long bone deformity but showing spontaneous prenatal and postnatal improvement. Design: TNSALP enzyme and substrate analysis and TNSALP mutation analysis were performed on all family members. Patients: A boy with HPP showing long bone deformity that spontaneously improved in utero and after birth is described. His older brother has the childhood form of HPP without findings until after infancy. His parents and twin sister are clinically unaffected. Results: Both boys are compound heterozygotes for the same missense mutations in TNSALP, documenting autosomal recessive inheritance for their HPP. The parents each carry one defective allele. Conclusions: The patient is an autosomal recessive case of HPP with prenatal long bone deformity but with spontaneous prenatal and postnatal improvement. Thus, prenatal detection by sonography of bowing of long bones from HPP, even with autosomal recessive inheritance, does not necessarily predict lethality but can represent variable expressivity or the effects of modifiers on the TNSALP defect(s).Keywords
This publication has 28 references indexed in Scilit:
- 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
- Marrow Cell Transplantation for Infantile HypophosphatasiaJournal of Bone and Mineral Research, 2003
- Correlations of genotype and phenotype in hypophosphatasiaHuman Molecular Genetics, 1999
- Phenotypically dissimilar hypophosphatasia in two sibshipsAmerican Journal of Medical Genetics, 1992
- Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism.JCI Insight, 1985
- Early prenatal diagnosis of congenital hypophosphatasia: Case reportPrenatal Diagnosis, 1985
- HypophosphatasiaMedicine, 1984
- THE EXCRETION OF PHOSPHOETHANOLAMINE AND HYPOPHOSPHATASIAThe Lancet, 1955