Renal Failure Associated with APECED and Terminal 4q Deletion: Evidence of Autoimmune Nephropathy

Abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). Terminal 4q deletion is also a rare cytogenetic abnormality that causes a variable syndrome of dysmorphic features, mental retardation, growth retardation, and heart and limb defects. We report a 12-year-old Saudi boy with mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical failure consistent with APECED. In addition, he has dysmorphic facial features, growth retardation, and severe global developmental delay. Patient had late development of chronic renal failure. The blastogenesis revealed depressed lymphocytes' response to Candida albicans at 38% when compared to control. Chromosome analysis of the patient revealed 46,XY,del(4)(q33). FISH using a 4p/4q subtelomere DNA probe assay confirmed the deletion of qter subtelomere on chromosome 4. Parental chromosomes were normal. The deleted array was further defined using array CGH. AIRE full gene sequencing revealed a homozygous mutation namely 845_846insC. Renal biopsy revealed chronic interstitial nephritis with advanced fibrosis. In addition, there was mesangial deposition of C3, C1q, and IgM. This is, to the best of our knowledge, the first paper showing evidence of autoimmune nephropathy by renal immunofluorescence in a patient with APECED and terminal 4q deletion.

Retinal degeneration in autoimmune polyglandular syndrome type 1: a case series

“…AIRE is expressed in the thymus and in secondary lymphoid organs, where it modulates the expression of peripheral antigens 22 . AIRE has a key role in preventing organ-specific autoimmunity involving autoantibodies 23. Pathogenic mutations in the AIRE gene lead to a perturbation of the immunological tolerance and hence give rise to autoimmune subversive processes against many target organs 20 22 23…”

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy

“…TIN is usually suspected on the basis of elevated serum creatinine, increased erythrocyte sedimentation rate, abnormal urinalysis, LMW proteinuria and glycosuria [27]. The autoimmune nature of renal destruction has been confirmed by examining biopsy samples showing T cell infiltration and by determining antiproximal tubular autoantibodies [11,27,121,122].…”

Oral Tongue Malignancies in Autoimmune Polyendocrine Syndrome Type 1

“…It is clinically defined by the presence of two of the three main components: hypoparathyroidism (HP), primary adrenocortical insufficiency (PAI), and chronic mucocutaneous candidiasis (CMC) ( 1 , 2 ), but several less known organ-specific manifestations are also part of the syndrome making the clinical phenotype highly variable ( 2 – 4 ). The overall mortality is increased ( 5 , 6 ) due to different complications such as acute adrenal crisis ( 3 , 5 ), severe pneumonitis with respiratory failure ( 7 – 9 ), fulminant autoimmune hepatitis ( 4 ), and interstitial nephritis causing renal failure ( 10 , 11 ).…”