Clinical and pathologic findings in hemochromatosis hip arthropathy

During a 9-year period, 15 patients with hemochromatosis hip arthropathy required 19 total hip arthroplasties for disabling hip pain. Preoperative presentation, hip function, pathologic evaluation of the femoral head, and radiographic findings were reviewed. Postoperative followup averaging 5.7 years (range, 2-11 years) was performed to assess hip pain and function after total hip arthroplasty. The average preoperative Hospital for Special Surgery hip score was 15 points (range, 4-24 points), and this improved to 30 points (range, 4-38 points) after total hip arthroplasty. Only one of 15 patients required revision surgery at 10 years for acetabular loosening. All other patients were pain free, with improved function at latest followup. Histologic evaluation of the resected femoral heads revealed evidence of primary or secondary osteonecrosis in seven of 19 (37%) specimens. Articular cartilage avulsion at the level of the tidemark was identified in eight of 19 (42%) specimens, and calcium pyrophosphate deposition was identified in five of 19 (26%) specimens. These pathologic findings suggest a predictable progression of the arthritic process in patients with hemochromatosis.     

Arthropathy in hemochromatosis

Early diagnosis of hemochromatosis may prevent the numerous risks of iron overload. One of the most common early manifestations of this disease is arthropathy. The clinical and radiologic findings of hemochromatosis arthropathy are discussed. Diagnosis is suggested by simple laboratory tests and confirmed by liver biopsy with measurement of hepatic iron content. Treatment includes the removal of the excess body iron by phlebotomy. Unfortunately, symptoms of arthropathy tend to be resistant to phlebotomy.     

Hereditary hemochromatosis

Genetic (hereditary) hemochromatosis is probably the most common autosomal recessive disorder found in white Americans, of whom about 5/1,000 (0.5 percent) are homozygous for the associated gene. The hemochromatosis gene is probably located close to the HLA-A locus on the short arm of chromosome 6. Homozygous individuals may develop severe and potentially lethal hemochromatosis, especially after age 39. Hereditary hemochromatosis involves an increased rate of iron absorption from the gut with subsequent progressive storage of iron in soft organs of the body. Excess iron storage eventually produces pituitary, pancreatic, cardiac, and liver dysfunction and death may result from cardiac arrhythmias, congestive heart failure, and/or hepatic failure or cancer. Early diagnosis can prevent these excess iron-induced problems. Iron overload owing to HLA-linked hereditary hemochromatosis can be distinguished from other causes of hemochromatosis by liver biopsies and interpretations. Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations. Family members of hereditary hemochromatosis patients are at increased risk and should be tested. Screening, identification and early treatment (phlebotomies, sometimes in combination with the use of Desferal or other iron-chelating agents) may help prevent or reduce iron-related organ damage and premature deaths. Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.     

Research priorities in hereditary hemochromatosis

The Working Group on Research Priorities used a formal nominal group technique to identify and prioritize the specific aims of applied research needed to provide the scientific basis for population screening for iron overload disorders. The most important applied research goal was characterization of the natural history of the relation between genotype and phenotype in hereditary hemochromatosis and other iron overload disorders. Three other important research objectives were development of an optimal approach to screening for iron overload; analyses of the cost-effectiveness of screening; and assessment of the ethical, legal, and social implications of screening. To achieve these specific aims, two research studies were recommended as being of the highest priority: a multicenter, cross-sectional, population-based study of the natural history of iron overload and a multicenter, case-control study of patients with disease manifestations potentially attributable to hereditary hemochromatosis in primary care and subspecialty clinics.     

Neonatal hemochromatosis]

Huge sacrococcygeal teratomas in the newborn can cause significant morbidity and even death due to cardiac failure, hemorrhage, or both. Surgical removal is the treatment of choice, but can indicate these events. Ligation of the median sacral artery, which always supplies the tumor, prior to its removal has been advocated, but in the past this procedure required a formal laparotomy. Nowadays, it can be easily accomplished laparoscopically, as this case report demonstrates.     

Genetic screening of hemochromatosis

A 62-year-old woman became progressively ill after aorto-bifemoral graft surgery. A Tc-99m hexamethylpropyleneamine oxime (HMPAO) leukocyte scan was performed because of fever and suspected graft infection. The anterior abdominal and pelvic views demonstrated marked uptake within the sigmoid colon. Follow-up studies, including CT scan and contrast intestinal x-rays, confirmed the presence of an abnormal sigmoid loop. Subsequent surgical resection and pathological examination of the sigmoid colon revealed ischemic changes. To our knowledge, detection of ischemic colitis using Tc-99m HMPAO labeled leukocytes has not been reported. Clinical and routine radiological findings of ischemic colitis are typically nonspecific and may result in delayed diagnosis that can lead to high mortality. Tc-99m HMPAO leukocyte scintigraphy may be helpful in the noninvasive diagnosis of ischemic injury to the colon, especially after aortic graft surgery.     

Corneal transplantation

Corneal transplantation is a highly successful procedure for restoring sight in patients with corneal disease. The most common indication for transplantation is corneal edema following cataract extraction. A common problem following corneal transplantation is astigmatism, which often requires thick lenses for correction. The excimer laser holds promise for correcting postoperative astigmatism but is not yet in wide use. Rejection is a life-long risk and is most likely to occur during the first year. Topical corticosteroids are commonly used to decrease this risk. Frank corneal rejection must be recognized early and treated with intensive topical therapy.     

Primary hemochromatosis and dietary iron

Primary haemochromatosis is characterized by an unusually high degree of iron absorption resulting in the accumulation of excessive amounts of tissue iron. Excess stores of iron are removed by repeated phlebotomy. Health personnel and a number of patients with primary haemochromatosis have expressed their desire for advice on special diets to try and reduce the number of phlebotomies per year. This article gives advice on how patients with primary haemochromatosis can decrease their dietary iron intake and how they can put together meals to obtain low bioavailability, and therefore a lower iron absorption. The diet should be varied and be rich in bread and cereals, and fruit and vegetables. The amount of meat, Norwegian brown whey cheese (iron supplemented) and alcohol should be limited. Tea or coffee with meals will reduce iron absorption. Food rich in ascorbic acid (fruit and fruit juice) should be avoided with meals. Ascorbic acid supplements are not recommended.     

Corneal transplantation in antibody-deficient hosts

PURPOSE: To examine the role of donor-specific antibodies, with or without complement, in rejection of orthotopic corneal transplants by using mice as recipients in which the genes for the heavy chain of immunoglobulin or the third complement component have been eliminated by homologous recombination. METHODS: BALB/c corneas were transplanted into eyes of B-cell-deficient (n=17) or wild-type control C57BL/6 (n=30) mice and into eyes of complement (C3)-deficient (n=15) or wild-type control 129-C57BL/6 (n=13) mice. After surgery all grafts were evaluated over 8 weeks in a masked manner by biomicroscopy for signs of rejection. RESULTS: The rates of corneal transplant rejection were similar among B-cell-deficient and C3-deficient mice compared with rejection rates in their respective wild-type control subjects. This similarity applied to the time course of rejection and to cumulative survival rates. CONCLUSIONS: Neither donor-specific antibody nor the third component of complement play essential roles in acute rejection of orthotopic corneal allografts in mice.     

Diagnosis of hemochromatosis probands in a community hospital

PURPOSE: To evaluate factors that lead to the diagnosis of hemochromatosis probands in a community hospital, including education of physicians about hemochromatosis and iron overload, specialty of physicians, diagnostic indicators of hemochromatosis, and clinical manifestations of hemochromatosis probands. PATIENTS AND METHODS: We conducted a hemochromatosis education program for health care personnel associated with a community hospital and the public during 1990 to 1994. Data on physicians who diagnosed probands, diagnostic indicators of hemochromatosis, and manifestations of hemochromatosis and associated illnesses were tabulated. Iron grades of all hospital liver biopsy specimens obtained from Caucasian subjects during 1990 to 1994 were also analyzed. RESULTS: We identified 162 hemochromatosis probands; 66.7% were diagnosed by physicians who participated in our education program. Primary care and internal medicine subspecialty physicians diagnosed 66.7% and 29.6% of probands, respectively, based on elevated serum iron parameters and hepatic enzyme concentrations (51.9% and 36.4% of probands, respectively). Iron overload occurred in 90.7%, and was associated with clinical manifestations in most. Of 844 hospital liver biopsy specimens from Caucasians, 8.5% had increased iron grades; 4.6% represented hemochromatosis. CONCLUSIONS: Physicians with current education readily diagnose hemochromatosis probands during routine health care delivery, but most probands identified in this manner have iron overload. Our results suggest that community physicians and hospitals could contribute substantially to hemochromatosis screening programs, permitting detection of more homozygotes before the development of iron overload.     

Corneal opacities in Gaucher disease

PURPOSE: To describe the corneal findings in a variant of Gaucher disease. METHODS: Case report. In an 18-year-old man, ophthalmic and general clinical evaluation, and enzymatic and molecular genetics studies were performed. RESULTS: Diffuse, well-defined, small, linear, or dotlike corneal opacities were observed through, out the posterior two thirds of the corneal stroma in both eyes. The patient had calcific valvular heart disease. Enzymatic and ultrastructural studies were consistent with Gaucher disease. Analysis of the glucocerebrosidase gene disclosed homozygosity for a D409H mutation. CONCLUSION: Corneal opacities are a distinguishing ocular feature of the variant of Gaucher disease associated with the D409H mutation and with calcific cardiac disease.