Reversible metaphyseal dysplasia, a novel bone phenotype, in two unrelated children with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy: clinical and molecular studies.

Abstract

We report the association of an undescribed, reversible metaphyseal dysplasia (RMD) with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in two patients, one homozygous and one heterozygous for a 13-bp deletion in exon 8 of the autoimmune regulator (AIRE) gene. One patient also had a novel deletion in exon 6, resulting in a frameshift mutation and introduction of a STOP codon in exon 10. Their APECED phenotypes differed, but both patients developed progressive skeletal deformities and growth failure from early childhood. Radiological examination suggested a generalized abnormality of endochondral ossification, with irregular, flared, radioopaque regions in the metaphyses, subjacent to the growth plates. Histopathology in patient 1 showed islands of calcified cartilage within bone, consistent with impaired coupling of cartilage resorption with vascular invasion and ossification. Despite discordance for puberty, both patients experienced radiological resolution of their bone disease in their mid-teens, with improvement in histopathology in patient 1. RMD may constitute a rare phenotypic variation of APECED, possibly resulting from autoimmunity directed against skeletal proteins. We also demonstrated AIRE expression in chondrocytes derived from human fetal growth plates, primary culture of human chondrocytes, and two chondrosarcoma cell lines, suggesting a potential role for abnormal AIRE expression in the development of RMD.

• Authors: Mark Harris, Ouafae Kecha, Cheri Deal, C Rolfe Howlett, Dorothee Deiss, Vivienne Tobias, Judith Simoneau-Roy, Jan Walker
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 88 Issue 10 Pg. 4576-85 (Oct 2003) ISSN: 0021-972X [Print] United States
• PMID: 14557425 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• APECED protein
• RNA, Messenger
• Transcription Factors

Topics

• Adult
• Biopsy
• Child
• Chondrocytes (cytology, physiology)
• Chondrosarcoma
• DNA Mutational Analysis
• Female
• Femur (diagnostic imaging, pathology)
• Gene Deletion
• Gene Expression
• Hand Deformities, Congenital (diagnostic imaging, epidemiology, genetics)
• Humans
• Immunohistochemistry
• Osteochondrodysplasias (complications, diagnostic imaging, genetics)
• Phenotype
• Polyendocrinopathies, Autoimmune (complications, diagnostic imaging, genetics)
• RNA, Messenger (analysis)
• Radiography
• Transcription Factors (genetics)
• Tumor Cells, Cultured