Case StudiesHeme oxygenase–1 deficiency: The first autopsy case*
Section snippets
Clinical summary
A 6-year-old boy was first admitted to our hospital at age 2 with recurrent fever, a generalized erythematous rash, and arthralgia. His growth was apparently retarded and he had marked hepatomegaly and cervical lymphadenopathy, but his spleen was not palpable. Abdominal ultrasonography and isotope imaging had proved him asplenic. There was no evidence to substantiate a presumptive diagnosis of juvenile rheumatoid arthritis on roentgenographic examination. Hematuria and proteinuria were
Pathologic findings
The body was 13 kg in weight and 86.5 cm in height. There was generalized edema, particularly in the face. Bloody ascites (80 mL) were observed, but there was no pleural or pericardial fluid. The liver was markedly enlarged, weighing 1,150 g, and a pale yellowish-tan in color. Light microscopically, amorphous substances were deposited in the sinusoidal space resulting in marked atrophy of hepatocytes (Fig 1A).
Discussion
HO-1 is a protein that not only degrades the hemoglobin-heme into biliverdin, but also acts as an anti-inflammatory protector against oxidative injurious stimuli. This is the reason why the clinical setup and laboratory data of the present case5 were complicated and a definite diagnosis was delayed. Previously, Poss and Tonegawa4 reported on HO-1–targeted mice, showing that they lack the ability to reuse iron and are characterized by anemia, tissue iron deposition, progressive chronic
Acknowledgements
The authors thank Drs Yoshinobu Hoshii and Tokuhiro Ishihara of the First Department of Pathology, Yamaguchi University School of Medicine, for immunohistochemical analysis of amyloidosis and helpful suggestions and Dr Shinya Toyokuni of the Department of Pathology, Graduate School of Medicine, Kyoto University, for immunohistochemical evaluation of 8-hydroxy-2'-deoxyguanosine.
References (15)
- et al.
Tubular injury as a cardinal pathologic feature in human heme oxygenase-1 deficiency
Am J Kidney Dis
(2000) - et al.
Expression of endothelial and inducible nitric oxide synthase in human glomerulonephritis
Kidney Int
(1998) The heme oxygenase system: A regulator of second messenger gases
Annu Rev Pharmacol Toxicol
(1997)Heme oxygenase: Function, multiplicity, regulatory mechanisms, and clinical applications
FASEB J
(1988)- et al.
Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3
Eur J Biochem
(1997) - et al.
Heme oxygenase 1 is required for mammalian iron reutilization
Proc Natl Acad Sci U S A
(1997) - et al.
Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency
J Clin Invest
(1999)
Cited by (0)
- *
Address correspondence and reprint requests to Atsuhiro Kawashima, MD, PhD, Department of Molecular and Cellular Pathology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640 Japan.