Elsevier

Human Pathology

Volume 33, Issue 1, January 2002, Pages 125-130
Human Pathology

Case Studies
Heme oxygenase–1 deficiency: The first autopsy case*

https://doi.org/10.1053/hupa.2002.30217Get rights and content

Abstract

This article describes the first autopsy case of heme oxygenase (HO)-1 deficiency. A 6-year-old boy who presented with growth retardation; anemia; leukocytosis; thrombocytosis; coagulation abnormality; elevated levels of haptoglobin, ferritin, and heme in serum; a low serum bilirubin concentration; and hyperlipidemia was diagnosed as HO-1 deficient by gene analysis several months before death. Autopsy showed amyloid deposits in the liver and adrenal glands and mesangioproliferative glomerular changes in kidneys, in addition to an irregular distribution of foamy macrophages with iron pigments. Fatty streaks and fibrous plaques were noted in the aorta. Compared with HO-1–targeted mice, the present case seems to more severely involve endothelial cells and the reticuloendothelial system, resulting in intravascular hemolysis, disseminated intravascular coagulation, and amyloidosis with a short survival. This contrasts to the predominant iron metabolic disorders of HO-1–targeted mice with a long survival. HUM PATHOL 33:125-130. Copyright © 2002 by W.B. Saunders Company

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).

. Histologic findings of liver. At autopsy, (A) a hematoxylin and eosin–stained

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.

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*

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.

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