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

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... formities 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. (J Clin Endocrinol Metab 88: 4576 -4585, 2003) Case Reports Patient 1 The first patient is one of three affected children in a siblingship of nine born to unrelated parents of differing European origins. Like her two affected brothers, she developed the classic triad of mucocutaneous candidiasis, hypo-Abbreviations: AIRE, Autoimmune regulator; APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; RMD, reversible metaphyseal dysplasia; RR, reference range; TRAP, tartrateresistant acid phosphatase; VEGF, vascular endothelial growth factor.