Survey and clinical application of serum iron, total iron binding capacity, transferrin saturation, and serum ferritin in captive black and white ruffed lemurs (Varecia variegata variegata).

Serum samples from 63 clinically normal captive black and white ruffed lemurs (Varecia variegata variegata) were analyzed to survey serum iron, total iron binding capacity, transferrin saturation, and serum ferritin levels. Data analysis showed no differences in these analytes attributable to sex, but significantly higher levels of serum iron, transferrin saturation, and serum ferritin in older animals. The survey data were examined in light of two black and white ruffed lemurs that were treated for iron overload with serial phlebotomies. Prior to therapy, both phlebotomized lemurs had excess hepatic iron deposition, but had serum iron, transferrin saturation, and serum ferritin below the upper limits observed in the survey animals, suggesting that some clinically normal animals included in the survey may have accumulated excess systemic iron. Serial phlebotomy therapy reduced serum iron, transferrin saturation, and serum ferritin in both animals. Three years after the conclusion of therapy in the one remaining case, serum iron and transferrin saturation have risen substantially, whereas serum ferritin has risen slightly. Serum iron, transferrin saturation, and serum ferritin may be useful predictors of systemic iron stores in this species, though the correlation between these parameters and systemic iron stores needs to be determined.     

Effect of oral administration of excessive iron in adult ponies

OBJECTIVE: To evaluate the potential of excess dietary iron to cause hepatic lesions similar to those described in horses with suspected iron toxicosis or hemochromatosis. DESIGN: Prospective study. ANIMALS: 6 adult male ponies. PROCEDURE: 4 ponies received 50 mg of iron/kg (22.7 mg/lb) of body weight each day by oral administration of ferrous sulfate, which contained 20% elemental iron; 2 ponies received only the carrier (applesauce). Complete blood counts, serum biochemical analyses, and hepatic tissue biopsies were performed, and serum iron concentrations were measured. Blood and tissue samples were obtained at days 0 and 2, and at the end of weeks 1, 3, 6, and 8 after administration of iron was initiated. Treatment was discontinued after 8 weeks, and hepatic iron concentrations were measured at 28 weeks. RESULTS: Hepatic iron concentrations, serum iron concentrations, percentage saturation of transferrin, and serum ferritin concentrations were increased, compared with baseline and control concentrations, by week 8. Adverse clinical signs or histologic lesions in the liver were not detected in any ponies. At 28 weeks, hepatic iron concentrations had decreased. CONCLUSIONS AND CLINICAL RELEVANCE: Histologic lesions were not seen in the hepatic biopsy specimens obtained from the ponies treated with ferrous sulfate. It was concluded that it would be unlikely for iron toxicosis to develop in adult ponies or horses during a period of < 8 weeks when food or water contained increased amounts of iron. It is suspected that previous reports of hepatopathies in animals with hemosiderin accumulation may represent a primary hepatopathy with secondary hemosiderin accumulation, especially if the only source of iron is via oral consumption.     

A Pasteurella-like bacterium associated with pneumonia in captive megachiropterans.

A novel Pasteurella-like organism was recovered postmortem from lung tissue of two captive Wahlberg's epauleted fruit bats (Epomophorus wahlbergi), with severe, unilateral pneumonia. The bats had been recently shipped and died shortly after release from a 30-day quarantine. One presented with clinical signs of anorexia and lethargy before death; the other died without prior clinical symptoms. The same Pasteurella-like organism was recovered antemortem from subcutaneous abscesses in two captive little golden mantled flying foxes (Pteropus pumilus) housed with additional E. wahlbergi. The organism was also cultured on tracheal wash from one Malaysian flying fox (Pteropus vampyrus) and another E. wahlbergi, both demonstrating clinical signs of pneumonia. All recovered isolates appeared morphologically and biochemically similar to the initial isolates and were further characterized as either a Pasteurella or Actinobacillus organism on the basis of biochemical and cellular fatty acid profiles. Screening of the current collection using pharyngeal swabs isolated this organism from 12 of 15 E. wahlbergi, two of three P. vampyrus, one of 26 island flying foxes (Pteropus hypomelanus), and one of nine Rodrigues fruit bats (Pteropus rodricensis). The organism was not identified in pharyngeal culture from eight Indian flying foxes (Pteropus giganteus), nine Egyptian fruit bats (Rousettus aegypticus), or an additional 16 P. pumilus.     

Evaluation of iron status in lemurs by analysis of serum iron and ferritin concentrations, total iron-binding capacity, and transferrin saturation

OBJECTIVE: To assess serum iron and ferritin concentrations, total iron-binding capacity, and transferrin saturation as indicators of iron metabolic status in 3 genera of lemurs and determine whether these variables are useful for screening for iron overload. DESIGN: Cross-sectional study. ANIMALS: 11 ring-tailed lemurs (Lemur catta), 11 black lemurs (Eulemur macaco macaco), and 11 red-ruffed lemurs (Varecia rubra). PROCEDURES: Blood samples were collected weekly for 3 weeks and assayed for serum iron and ferritin concentrations and total iron-binding capacity. Liver biopsy specimens were evaluated histologically and assayed for total iron, nonheme iron, and trace mineral concentrations. Deposition of iron was scored on Prussian blue-stained slides. RESULTS: Hepatic iron content ranged from 497 to 12,800 Pg/g dry weight (median, 2,165 Pg/g). Differences were seen in mean hepatic iron content across genera, with ruffed lemurs having the highest concentrations and ring-tailed lemurs having the lowest. Iron accumulation in the liver was mild, and cellular pathologic changes associated with iron storage disease were not detected in any lemur. Ferritin concentration was the only variable that correlated significantly with hepatic iron content in all 3 genera of lemurs; however, both transferrin saturation and serum iron concentration were correlated with hepatic iron concentration in ring-tailed and ruffed lemurs. CONCLUSIONS AND CLINICAL RELEVANCE: Serum ferritin concentration was the only variable that was consistently correlated with hepatic iron content in all 3 genera. Mean hepatic iron content varied across genera, suggesting that the propensity for lemurs to develop iron overload in captivity may vary across taxa.     

Potential effects of glucocorticoids on serum iron concentration in dogs

Prednisone was give norally(2mg/kg b.i.d.) to seven healthy mixed breed dogs for 3 consecutive days. Serum iron concentration increased significantly (p < 0.05) from 142 +/- 26 micro g/dl (mean +/- SE) before a drug adminis- tration on Day 0 to a maximum of 307 +/- 47 micro g/dl on Day 2, and returned to the Day 0 value by Day 5. Mean total iron binding capacity did not vary more than 25% from the Day 0 value during the 9 day long study. The percent saturation of transferrin with iron increased from 33 +/- 6% on Day 0 to a maximum of 71 +/- 9% on Day 3. This determination had decreased to 34 +/- 3% on Day 5. No statistically significant changes occurred in these parameters studied in six control dogs that were not given the drug. To determine whether serum iron concentration might be correlated with endogenous serum cortisol concentration, these tests were determined in serum collected from nine dogs at 7 a.m., 3 p.m., and 11 p.m. each day for 3 consecutive days. Serum iron concentration was lower at 7 a.m. (147 +/- 9 micro g/dl) than at 3 p.m. (164 +/- 9 micro g/dl) or 11 p.m. (159 +/- 10 micro g/dl). Likewise serum cortisol was lower at 7 a.m. (1.29 +/- 0.18 micro g/dl) than at 3 p.m. (1.49 +/- 0.19 micro g/dl) or 11 p.m. (1.51 +/- 0.22 micro g/dl). There was a significant positive linear correlation between serum iron and serum cortisol concentrations when they were compared using mean values for each dog. From these studies, it appears that exogenously administered glucocorticoids and endogenous increases in serum cortisol concentrations may result in increased serum iron concentrations in dogs.     

Characterization of the hepcidin gene in eight species of bats

Hemochromatosis, or iron storage disease, has been associated with significant liver disease and mortality in captive Egyptian fruit bats (Rousettus aegyptiacus). The physiologic basis for this susceptibility has not been established. In humans, a deficiency or resistance to the iron regulatory hormone, hepcidin has been implicated in the development of hereditary hemochromatosis. In the present study, we compared the coding sequence of the hepcidin gene in eight species of bats representing three distinct taxonomic families with diverse life histories and dietary preferences. Bat hepcidin mRNA encoded a 23 amino acid signal peptide, a 34 or 35 amino acid pro-region, and a 25 amino acid mature peptide, similar to other mammalian species. Differences in the sequence of the portion of the hepcidin gene that encodes the mature peptide that might account for the increased susceptibility of the Egyptian fruit bat to iron storage disease were not identified. Variability in gene sequence corresponded to the taxonomic relationship amongst species.     

Plasma biochemistry and hematologic values for wild-caught flying foxes (Pteropus giganteus) in India.

Although bats of the genus Pteropus are important ecologically as pollinators and natural hosts for zoonotic pathogens, little is known about their basic physiology. Hematology and plasma biochemistries were determined from wild-caught flying foxes (Pteropus giganteus) in northern India (n=41). Mean lymphocyte differential count was higher for juveniles than adults. Mean platelet count was lower than previously reported. No hemoparasites were observed. No differences were observed between plasma biochemistry values of male and female bats, juveniles and adults, or lactating and nonlactating females. Variation in aspartate aminotransferase (AST) was seen based on body condition score. Blood urea nitrogen and cholesterol concentrations were lower in P. giganteus than other mammalian groups, but were consistent with those reported from other Pteropus species. Alanine aminotransferase and AST concentrations were higher than those reported for Pteropus vampyrus, a closely related species. This study provides basic physiologic information that can be used in future health and disease studies of Indian flying foxes.     

The postnatal iron status of trotter foals

The postnatal iron status of 20 trotter foals (7 female, 13 male) was studied by analyzing different parameters in blood drawn on the day of birth, and 14 +/- 2 and 28 +/- 2 days later. Hemoglobin hematocrit, plasma iron and transferrin saturation averaged 14.9 g/dl, 41.8%, 300 micrograms/dl and 59.4%, respectively, on the day of birth. These values were significantly reduced after 14 days, but had approached again the initial levels by day 28. There was a slight, statistically nonsignificant rise in the mean total iron-binding capacity over the four-week period. Iron status was not affecting by the sex of the foals. On the day of parturition, the mares had much lower levels of plasma iron and transferrin saturation than their foals. In the discussion, the importance of checking the iron status of each individual foal during the critical period of the first 14 days post partum is stressed.     

Radiographic evaluation of cardiac size in flying fox species (Pteropus rodricensis, P. hypomelanus, and P. vampyrus).

Dilated cardiomyopathy is a relatively common pathology in captive flying foxes (Pteropus spp.). The goal of this study was to establish quantitative reference range measurements that could be used to support a diagnosis of cardiac disease in these animals. Lateral and ventrodorsal thoracic radiographs from apparently healthy flying foxes (n = 66) of three species (Rodriguez island flying fox, P. rodricensis, n = 18; small island flying fox, P. hypomelanus, n = 16; and Malaysian flying fox, P. vampyrus, n = 32) were evaluated objectively to describe the cardiac appearance. Absolute and relative cardiac dimensions also were measured. The same methods were used to evaluate radiographs from flying foxes (n = 9) with known dilated or acute cardiomyopathy. The following ratios were most appropriate for categorizing normal cardiac silhouette size. In the ventrodorsal projection, heart width to thoracic width and heart width to clavicle length were the preferred measurements. In the lateral projection, heart width compared with thoracic height was the preferred measurement. From radiographs of the bats with known dilated and acute cardiomyopathy, the apicobasilar heart length compared with thoracic height and heart width compared with thoracic height on lateral films were the most sensitive ratios for diagnosing cardiomegaly.     

Neuro-angiostrongylosis in wild Black and Grey-headed flying foxes (Pteropus spp)

OBJECTIVE: To identify nematodes seen in histological sections of brains of flying foxes (fruit bats) and describe the associated clinical disease and pathology. PROCEDURES: Gross and histological examination of brains from 86 free-living flying foxes with neurological disease was done as part of an ongoing surveillance program for Australian bat lyssavirus. Worms were recovered, or if seen in histological sections, extracted by maceration of half the brain and identified by microscopic examination. Histological archives were also reviewed. RESULTS: There was histological evidence of angiostrongylosis in 16 of 86 recently submitted flying foxes with neurological disease and in one archival case from 1992. In 10 flying foxes, worms were definitively identified as Angiostrongylus cantonensis fifth-stage larvae. A worm fragment and third stage larvae were identified as Angiostrongylus sp, presumably A cantonensis, in a further three cases. The clinical picture was dominated by paresis, particularly of the hindlimbs, and depression, with flying foxes surviving up to 22 days in the care of wildlife volunteers. Brains containing fifth-stage larvae showed a moderate to severe eosinophilic and granulomatous meningoencephalitis (n = 14), whereas there was virtually no inflammation of the brains of bats which died when infected with only smaller, third-stage larvae (n = 3). There was no histological evidence of pulmonary involvement. CONCLUSION: This is the first report of the recovery and identification of A cantonensis from free-living Australian wildlife. While angiostrongylosis is a common cause of paresis in flying foxes, the initial clinical course cannot be differentiated from Australian bat lyssavirus infection, and wildlife carers should be urged not to attempt to rehabilitate flying foxes with neurological disease.     

Role of excessive maternal iron in the pathogenesis of congenital leukoencephalomalacia in captive black rhinoceroses (Diceros bicornis)

OBJECTIVE: To investigate the possibility that excessive maternal iron (overload) may contribute to development of congenital leukoencephalomalacia in captive black rhinoceroses. SAMPLE POPULATION: Tissue specimens and serum samples from 18 rhinoceroses in 2 kindreds harboring 4 (possibly 5) affected female calves. PROCEDURE: Fresh and archival sera and necropsy tissue specimens were evaluated to determine the nature and extent of iron overload in captive and wild black rhinoceroses as well as other rhinoceros species. RESULTS: Quantitative serum and tissue assays of iron and iron analytes, corroborated by histopathologic findings, indicated that these kindreds carried the greatest body burdens of iron yet found among captive black rhinoceroses. Fourteen of 18 rhinoceroses had the highest serum ferritin concentrations measured among 64 black rhinoceroses in captivity in the United States. Dams of affected calves had serum ferritin concentrations 2 orders of magnitude higher than clinically normal humans, equids, or free-ranging rhinoceroses. A neonatal serum sample from 1 affected female calf had a high ferritin concentration (approx 100-fold increase), but a male sibling of another affected female did not, suggesting a possible sex disparity in fetal response to maternal iron overload. Morphologic hallmarks of hemochromatosis were prominent in dams and grandams of affected calves. CONCLUSIONS AND CLINICAL RELEVANCE: Excessive maternal iron may affect female fetuses more than males, possibly inducing leukoencephalomalacia by catalyzing production of highly toxic hydroxyl free radicals during crucial periods of in utero development. Reduction of maternal iron overload may decrease the probability of developing leukoencephalomalacia and some other disorders commonly affecting rhinoceroses in captivity.     

Canine liver iron, copper, and zinc concentrations and association with histologic lesions.

Concentrations of iron, copper, and zinc were measured in livers of 95 dogs that were suspected of having liver disease. Iron concentrations ranged from 177 to 7,680 ppm (dry weight basis); 54 dogs had iron concentrations greater than the normal concentration of 1,200 ppm. Iron stores were present in Kupffer cells and macrophages but not hepatocytes. The dogs did not have lesions of hemochromatosis. Dogs with high liver iron tended to have high liver copper and inflammatory lesions. High liver copper concentrations usually were associated with hepatocellular necrosis and fibrosis. High liver zinc was found in only 5 animals and was accompanied by histologic inflammatory lesions in one. In humans, increased iron concentration in the liver exacerbates liver damage caused by a variety of insults, and the same may be true for dogs.     

Iron content of rat serum ferritin.

The serum ferritin concentration was significantly higher in female than in male rats, reflecting higher iron stores in females than in males. The mean iron/protein ratio of serum ferritin was 0.018+/-0.008 (SD) (microg of Fe/microg of protein) in female rats and 0.011+/-0.011 in male rats, being much lower than that of liver ferritin (0.233+/-0.014 in females and 0.227+/-0.020 in males). Iron loading of rats significantly increased serum ferritin concentration, but did not influence the iron content of serum ferritin. These results indicate that rat serum ferritin contains only a small amount of iron independent of body iron stores.     

Serum zinc, chromium, and iron concentrations in dogs with lymphoma and osteosarcoma

We compared serum concentrations of zinc, chromium, and iron in dogs with cancer to those of normal dogs. Dogs with lymphoma (n = 50) and osteosarcoma (n = 52) were evaluated. Dogs with lymphoma had significantly lower (P = .0028) mean serum zinc concentrations (mean +/- SD; 1.0 +/- 0.3 mg/L) when compared to normal dogs (1.2 +/- 0.4 mg/L). Dogs with osteosarcoma also had lower mean serum zinc concentrations (1.1 +/- 0.4 mg/L), but this difference was not significant (P = .075). Serum chromium concentrations were significantly lower in dogs with lymphoma (2.6 +/- 2.6 microg/L, P = .0007) and osteosarcoma (2.4 +/- 3.1 microg/L, P = .0001) compared to normal dogs (4.7 +/- 2.8 microg/L). Serum iron concentrations and total iron-binding capacity were significantly lower in dogs with lymphoma (110.8 +/- 56.7 microg/dL, P < .0001, and 236.6 +/- 45.6 microg/dL, P < .0001, respectively) and osteosarcoma (99.6 +/- 49.3 microg/dL, P < .0001, and 245.0 +/- 43.8 microg/dL, P = .0011, respectively) when compared to normal dogs (175.1 +/- 56.7 microg/dL and 277.1 +/- 47.4 microg/dL). Mean ferritin concentration was significantly higher in dogs with lymphoma (1291.7 +/- 63.0 microg/L) than in normal dogs (805.8 +/- 291.1 microg/L, P < .0001) and dogs with osteosarcoma (826.5 +/- 309.2 microg/L, P < .0001). Further investigation is needed to explore the clinical significance of these mineral abnormalities in dogs with cancer.     

Seminal plasma lactoferrin but not transferrin reflects gonadal function in dogs

Lactoferrin purified from canine seminal plasma by a three-step chromatography procedure had a molecular mass of 75.2 kDa and cross-reacted with antiserum to equine seminal plasma lactoferrin. Seminal plasma lactoferrin concentrations were determined by a competitive enzyme-linked immunosorbent assay (ELISA) by using rabbit anti-equine lactoferrin antibody and alkaline phosphatase-labeled goat anti-rabbit IgG antibody in 14 normal dogs and found to range from 12 to 197 micro g/ml, with a mean value of 77 +/- 59 micro g/ml (the mean +/- SD). Seminal plasma transferrin concentrations were determined by a sandwich ELISA with goat antibody to canine serum transferrin and alkaline phosphatase-conjugated goat anti-canine transferrin antibody and found to range from 0.32 to 12.6 micro g/m l, with a mean value of 2.44 +/- 3.25 micro g/m l. The lactoferrin concentration significantly correlated with the sperm concentration (r=0.7025, P<0.01), but there was no significant correlation between the seminal plasma transferrin concentration and sperm density. These results indicate that seminal plasma lactoferrin, but not transferrin, reflects gonadal function.     

Hemochromatosis in Salers Cattle

Two 2-year-old Salers cattle from different herds raised on pasture were evaluated for retarded growth and diarrhea. Increase of liver enzyme activities and prolonged sulfobromophothalein (BSP) half life (T1/2) indicated liver disease with impaired liver function. Histopathologic examination of liver biopsies revealed a micronodular cirrhosis with marked deposition of hemosiderin in hepatocytes, Kupffer cells, and arterioles. Transferrin saturation (TS) and liver iron content were markedly increased, consistent with a diagnosis of hemochromatosis. Both animals were euthanatized due to deterioration in their condition. Necropsy findings included hepatomegaly and hemosiderin accumulation in the liver, lymph nodes, pancreas, spleen, thyroid, kidney, brain and other glandular tissue. Continued surveillance of the second herd (serum iron, total iron binding capacity [TIBC], unsaturated iron binding capacity [UIBC], and TS), identified a heifer as a hemochromatosis suspect in a subsequent generation. Liver biopsies from that animal revealed the same histopathologic changes as the previous 2 animals, and similar increases in liver iron content (8,700 ppm, normal range 45 to 300 ppm). The 3 affected cattle were all products of line breeding programs and shared a common ancestor. The absence of dietary iron loading in conjunction with the histopathologic and metabolic findings were consistent with a diagnosis of primary hemochromatosis. The reported disease is similar to idiopathic hemochromatosis in human beings in which there is a hereditary defect in iron metabolism.     

Serum ferritin, serum iron, and erythrocyte values in foals

Twenty-one healthy Thoroughbred and Quarter Horse foals were studied from birth until 1 year of age. Foals had access to an iron-supplemented creep feed before weaning and were fed an iron-supplemented concentrate as part of their diet after weaning at 4 months of age. Initial blood samples were taken before foals were allowed to nurse. Serum iron concentration, total iron-binding capacity, and PCV decreased during the foal's first 24 hours of life. Serum iron concentration decreased rapidly from 446 +/- 16 micrograms/dl (mean +/- SE) at birth to 105 +/- 11 micrograms/dl at 3 days of age. Serum ferritin concentration increased from a mean of 85 +/- 8 ng/ml at birth to 159 +/- 11 ng/ml at 1 day of age. Thereafter, ferritin concentration decreased gradually to a minimum of 61 +/- 6 ng/ml at 3 weeks of age, and then at 6 months increased to values similar to those from reference adult horses. The ferritin concentration in colostrum at birth was 354 +/- 42 ng/ml, compared with 25 +/- 2 ng/ml in milk 1 day later. The decrease and then increase in serum ferritin concentration occurred concomitantly with opposite changes in serum total iron-binding capacity. The mean PCV decreased gradually to a minimum at 3 months of age. This decrease was associated with an increasing number of microcytes, as determined with a cell-size distribution analyzer.     

Effects of different iron contents in the milk replacer on the development of iron deficiency anaemia in veal calves.

The effect of different iron concentrations in the milk replacer on the development of iron deficiency anaemia during a fattening period of 28 weeks was studied in three groups of 14 calves. The iron contents in the milk replacer differed during the first seven weeks: 60, 100 and 150 mg Fe/kg in groups A, B and C, respectively. In all three groups blood haemoglobin, mean corpuscular volume, plasma iron concentration and saturation decreased during the fattening period, whereas the total iron-binding capacity increased. At week 7, liver iron concentrations were high with a large individual variation [A: 201 (61-706), B: 99 (47-129), C: 296 (77-1572) micrograms/g dry matter]. During the fattening period, liver iron concentrations decreased, with the lowest values at week 25 [A: 54 (34-82), B: 55 (44-83), C: 57 (42-79) micrograms/g dry matter]. Muscle iron concentrations decreased between week 7 and 19. Except plasma iron and saturation in group C, no differences in haematological and tissue iron variables were found throughout the fattening period in spite of different iron contents in the milk replacer during the first seven weeks.     

Relationship of serum ferritin and iron concentrations and serum total iron-binding capacity to nonheme iron stores in dogs

The relationships of various iron-related analytes were evaluated in 95 dogs. Liver and spleen nonheme iron content was determined coulometrically on acid-digested tissue specimens. Serum iron concentration and total iron-binding capacity also were measured coulometrically, whereas serum ferritin concentration was measured by ELISA. Significant (P less than 0.0002) correlation was found between serum ferritin concentration and nonheme iron stores. Significant correlation was not found between nonheme iron stores and serum iron concentration or total iron-binding capacity. Serum ferritin concentration should provide a convenient and relatively noninvasive means of estimating iron stores in dogs.     

Hepatic failure and hemochromatosis of Salers and Salers-cross cattle

Hemochromatosis is rare in domestic mammals. Five clinical cases and one preclinical case of hemochromatosis were diagnosed in Salers and Salers-cross cattle. Clinical disease developed between 9 and 22 months of age. Animals were healthy until weaning but then lost weight, developed rough hair coats, and lost incisor teeth. In two animals, hemochromatosis was identified by liver biopsy, biochemical evidence of hepatic injury, and/or elevated transferrin saturation values. At necropsy, carcasses were thin, with firm dark brown livers and lymph nodes, soft bones, and brown-colored small bowel. The principal histologic changes were hepatocellular siderosis and periportal, bridging, and perivenular fibrosis. Siderocalcinosis involved collagen, elastin, reticulin, and basement membrane components in liver, lymph nodes, spleen, duodenum, and kidney. Hepatic iron concentrations in clinically affected cattle were 1,500-10,500 microg/g wet weight (reference range for cattle = <300 microg/ g). Ultrastructurally, the heaviest intrahepatic deposition was in hepatocytes, which contained large intracytoplasmic siderosomes. Iron deposition in bone was associated with osteopenia. Genetic analysis indicated a common ancestral bull in the pedigrees of five of six affected cattle; no pedigree was available for the remaining animal. Four dams of five affected animals were phenotypically normal and had histologically normal livers. Test mating of four cows to the ancestral bull resulted in a female calf that developed clinicopathologic and histologic evidence of preclinical hemochromatosis by 40 days of age. It was not possible to establish the pattern of inheritance because of the small number of pedigrees from affected cattle.