| Research Abstract |
The first-described case of heme oxygenase-1 (HO-1) deficiency is presented. The patient, a 6-year-old boy, completely lacks HO-1, having a deletion of exon 2 of the maternal allele and a two-base-pair deletion in exon 3 of the paternal allele of the gene. Further analysis revealed structural evidence of genomic exon-deletion mediated by Alu-Alu recombination in this case. Similar to recently described HO-1 knockout mice, the boy exhibits severe growth retardation, anemia, iron deposition in renal and hepatic tissue, and vulnerability to stress-related injury. Mesangial change in glomerular capillary-wall thickness was shown in the three consecutive biopsy specimens. Electron microscopic examination showed widespread endothelial detachment and subendothelial deposits of an unidentifiable material. It was striking that tubulointerstitial injury, with tubular dilatation and/or atrophy, interstitial fibrosis, and inflammatory cell infiltration, advanced progressively. In addition, the boy exhibited morphological abnormality of monocytes and significant reduction of their surface molecules including CD11b, CD14, CD16 and CD36, resulting in a markedly impaired phagocytosis of monocytes.
Heme oxygenase, which catalyzes the conversion of heme into carbon monoxide and biliverdin, plays an important anti-inflammatory role in oxidative injury. The two known isoforms differ in their expression pattern, with HO-2 constitutively expressed in brain and testis, and HO-1 expressed ubiquitously at low levels, although it is rapidly induced following various stresses. The importance of the current work may lie less in its being the first described case of human HO-1 deficiency than in the clues it provides to the normal functions of this important enzyme.
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