CONCURRENT IRON OVERLOAD AND NEOPLASIA IN LESCHENAULT'S ROUSETTES (ROUSETTUS LESCHENAULTII): A CASE SERIES.

This case series investigates a cluster of deaths in a captive colony of Leschenault's rousettes (Rousettus leschenaultii). Six of seven bats that died between March and September 2021 were diagnosed postmortem with both iron overload (IO) and neoplasia, neither of which have previously been reported in this species. Iron status was assessed via hepatic histopathological grading, hepatic iron concentration, and, in two cases, serum iron concentration. On histopathological grading, all cases had hemochromatosis except one, which had hemosiderosis. Hepatic iron concentrations did not correlate with histopathological grading. Neoplasms in these six bats included hepatocellular carcinoma (HCC; 4), bronchioloalveolar adenocarcinoma (1), pancreatic adenocarcinoma (1), and sarcoma of the spleen and stomach (1). One bat had two neoplasms (HCC and sarcoma of the spleen and stomach). One additional case of HCC in 2018 was identified on retrospective case review. Etiology was investigated to the extent possible in a clinical setting. Nutritional analysis and drinking water testing found oral iron intake within acceptable bounds; however, dietary vitamin C was potentially excessive and may have contributed to IO. Panhepadnavirus PCR testing of liver tissue was negative for all bats. A species-associated susceptibility to IO, as seen in Egyptian fruit bats (Rousettus aegyptiacus), is possible. The high incidence of HCC is suspected to be related to IO; other differentials include viral infection. Causes or contributing factors were not definitively identified for the other neoplasms seen but could include age, inherited risk (given a high level of inbreeding), or an oncogenic virus. Pending further research in this species, it is recommended that keepers of Leschenault's rousettes offer conservative amounts of vitamin C and iron (as for Egyptian fruit bats), submit for postmortem examination any euthanized or found dead, and share records of similar cases.

Hepatocellular carcinoma with lung metastasis showing hemochromatosis in an Egyptian fruit bat (Rousettus aegyptiacus).

After an Egyptian fruit bat (Rousettus aegyptiacus) in a zoo became emaciated and died, a necropsy revealed multiple nodules on the liver and lung surfaces. Microscopy revealed that the liver nodules consisted of neoplastic hepatocytes and showed metastasis in the lung lobes. Most of the neoplastic cells in the liver and lung showed positive labeling for HepPar-1, cytokeratin 19, glypican-3, and Ki-67. Hepatocellular degeneration and necrosis were diffuse in the liver parenchyma. Berlin blue staining revealed large amounts of iron in normal and neoplastic cells. Based on these pieces of evidence, this case was diagnosed as hepatocellular carcinoma with hemochromatosis. This is believed to be the first report of hepatocellular carcinoma in an Egyptian fruit bat that has been immunophenotypically examined in detail by pathological examination.

A RETROSPECTIVE STUDY OF HEPATIC HEMOSIDEROSIS AND IRON STORAGE DISEASE IN SEVERAL CAPTIVE AND FREE-RANGING AVIAN SPECIES.

Some wild species of mammals and birds are prone to excessive iron accumulation, especially when maintained in human care. Hemosiderosis is the process of intracellular accumulation of iron without evidence of toxicity, whereas hemochromatosis is characterized by severe iron accumulation with accompanying organ damage. Iron storage disease (ISD) occurs when organ damage is severe and causing clinical signs. This retrospective study investigated the occurrence of hemosiderosis and ISD across a variety of avian taxa, including captive and free-ranging birds. Archived paraffin-embedded hepatic samples from 103 birds from Belo Horizonte Zoo that died naturally in the period of 2008 to 2018 were re-evaluated with histologic and morphometric techniques, focusing on the identification and scoring of iron deposits in hepatocytes and the quantification of total affected hepatic area. The birds represented 13 orders, 22 families, and 52 genera, and 66 (64.0%) had some degree of iron accumulation in their liver. Importantly, no statistical difference was observed in the occurrence of iron accumulation between families, orders, or origin (free-ranging or captive). Direct and positive correlation was observed between the total area affected by the iron deposits and the histologic score. In this study, there were two cases with severe iron accumulation and clinical signs compatible with ISD: a barefaced curassow (Crax fasciolata) and a channel-billed toucan (Ramphastos vitellinus). This study indicates that iron accumulation may occur in a wide range of avian species, with frequencies and intensities that are similar between free-ranging birds and those in human care. It describes for the first time the occurrence of ISD in a Galliform species.

PATHOLOGIC FINDINGS IN 36 SLOTHS FROM BRAZIL.

Sloths are xenarthrans from Central and South America with a highly adapted morphophysiology. Five of the six known species of sloths are found in Brazil, among which Bradypus torquatus (maned three-toed sloth) is considered a vulnerable species by International Union for Conservation of Nature. Nevertheless, knowledge on health and disease of sloths is very scarce, thus this study aimed to describe macroscopic and microscopic findings in 36 Brazilian sloths. The most common findings included iron storage disorder, probable bacterial pneumonia, gastric and intestinal nematode parasitism, and a presumptive diagnosis of systemic mastocytosis.

IRON STORAGE DISEASE IN AFRICAN GREY PARROTS ( PSITTACUS ERITHACUS) EXPOSED TO A CARNIVOROUS DIET.

Within a 2-wk period, three African grey parrots ( Psittacus erithacus) presented for emergency treatment. All three parrots had depressed behavior, an inability to fly, and significant weight loss. Plasma chemistry abnormalities included severe hypoproteinemia and elevated liver enzymes in all parrots. Two of the parrots died, and histologic examination with hematoxylin and eosin and Prussian blue stains revealed severe hepatic iron storage. Quantitative analysis confirmed high hepatic iron concentrations. Iron accumulation was attributed to ingestion of a carnivorous bird diet or selectively eating too much fruit and vegetables high in ascorbic acid. Management entailed husbandry changes including switching the remaining parrots to a low-iron diet. Psittacine species exposed to carnivorous bird diets are at risk of developing iron storage disease.

Iron storage disease (hemochromatosis) and hepcidin response to iron load in two species of pteropodid fruit bats relative to the common vampire bat.

Hepcidin is the key regulator of iron homeostasis in the body. Iron storage disease (hemochromatosis) is a frequent cause of liver disease and mortality in captive Egyptian fruit bats (Rousettus aegyptiacus), but reasons underlying this condition are unknown. Hereditary hemochromatosis in humans is due to deficiency of hepcidin or resistance to the action of hepcidin. Here, we investigated the role of hepcidin in iron metabolism in one species of pteropodid bat that is prone to iron storage disease [Egyptian fruit bat (with and without hemochromatosis)], one species of pteropodid bat where iron storage disease is rare [straw-colored fruit bat (Eidolon helvum)], and one species of bat with a natural diet very high in iron, in which iron storage disease is not reported [common vampire bat (Desmodus rotundus)]. Iron challenge via intramuscular injection of iron dextran resulted in significantly increased liver iron content and histologic iron scores in all three species, and increased plasma iron in Egyptian fruit bats and straw-colored fruit bats. Hepcidin mRNA expression increased in response to iron administration in healthy Egyptian fruit bats and common vampire bats, but not in straw-colored fruit bats or Egyptian fruit bats with hemochromatosis. Hepcidin gene expression significantly correlated with liver iron content in Egyptian fruit bats and common vampire bats, and with transferrin saturation and plasma ferritin concentration in Egyptian fruit bats. Induction of hepcidin gene expression in response to iron challenge is absent in straw-colored fruit bats and in Egyptian fruit bats with hemochromatosis and, relative to common vampire bats and healthy humans, is low in Egyptain fruit bats without hemochromatosis. Limited hepcidin response to iron challenge may contribute to the increased susceptibility of Egyptian fruit bats to iron storage disease.

SERUM FERRITIN CONCENTRATION IS NOT A RELIABLE BIOMARKER OF IRON OVERLOAD DISORDER PROGRESSION OR HEMOCHROMATOSIS IN THE SUMATRAN RHINOCEROS (DICERORHINUS SUMATRENSIS).

The aim of this study was to determine if ferritin is a reliable biomarker of iron overload disorder (IOD) progression and hemochromatosis in the Sumatran rhinoceros (Dicerorhinus sumatrensis) by developing a species-specific ferritin assay and testing historically banked samples collected from rhinos that did and did not die of hemochromatosis. Ferritin extracted from Sumatran rhino liver tissue was used to generate antibodies for the Enzyme Immunoassay. Historically banked Sumatran rhino serum samples (n = 298) obtained from six rhinos in US zoos (n = 290); five rhinos at the Sumatran Rhino Conservation Centre in Sungai Dusun, Malaysia (n = 5); and two rhinos in Sabah, Malaysia (n = 3) were analyzed for ferritin concentrations. Across all US zoo samples, serum ferritin concentrations ranged from 348 to 7,071 ng/ml, with individual means ranging from 1,267 (n = 25) to 2,604 ng/ml (n = 36). The ferritin profiles were dynamic, and all rhinos exhibited spikes in ferritin above baseline during the sampling period. The rhino with the highest mean ferritin concentration did not die of hemochromatosis and exhibited only mild hemosiderosis postmortem. A reproductive female exhibited decreases and increases in serum ferritin concurrent with pregnant and nonpregnant states, respectively. Mean (±SD) serum ferritin concentration for Sumatran rhinos in Malaysia was high (4,904 ± 4,828 ng/ml) compared to that for US zoo rhinos (1,835 ± 495 ng/ml). However, those in Sabah had lower ferritin concentrations (1,025 ± 52.7 ng/ml) compared to those in Sungai Dusun (6,456 ± 4,941 ng/ml). In conclusion, Sumatran rhino serum ferritin concentrations are dynamic, and increases often are not associated with illness or hemochromatosis. Neither a specific pattern nor the individual's overall mean ferritin concentration can be used to accurately assess IOD progression or diagnose hemochromatosis in this rhino species.

Feasibility Study of NMR Based Serum Metabolomic Profiling to Animal Health Monitoring: A Case Study on Iron Storage Disease in Captive Sumatran Rhinoceros (Dicerorhinus sumatrensis).

A variety of wildlife species maintained in captivity are susceptible to iron storage disease (ISD), or hemochromatosis, a disease resulting from the deposition of excess iron into insoluble iron clusters in soft tissue. Sumatran rhinoceros (Dicerorhinus sumatrensis) is one of the rhinoceros species that has evolutionarily adapted to a low-iron diet and is susceptible to iron overload. Hemosiderosis is reported at necropsy in many African black and Sumatran rhinoceroses but only a small number of animals reportedly die from hemochromatosis. The underlying cause and reasons for differences in susceptibility to hemochromatosis within the taxon remains unclear. Although serum ferritin concentrations have been useful in monitoring the progression of ISD in many species, there is some question regarding their value in diagnosing hemochromatosis in the Sumatran rhino. To investigate the metabolic changes during the development of hemochromatosis and possibly increase our understanding of its progression and individual susceptibility differences, the serum metabolome from a Sumatran rhinoceros was investigated by nuclear magnetic resonance (NMR)-based metabolomics. The study involved samples from female rhinoceros at the Cincinnati Zoo (n = 3), including two animals that died from liver failure caused by ISD, and the Sungai Dusun Rhinoceros Conservation Centre in Peninsular Malaysia (n = 4). Principal component analysis was performed to visually and statistically compare the metabolic profiles of the healthy animals. The results indicated that significant differences were present between the animals at the zoo and the animals in the conservation center. A comparison of the 43 serum metabolomes of three zoo rhinoceros showed two distinct groupings, healthy (n = 30) and unhealthy (n = 13). A total of eighteen altered metabolites were identified in healthy versus unhealthy samples. Results strongly suggest that NMR-based metabolomics is a valuable tool for animal health monitoring and may provide insight into the progression of this and other insidious diseases.

A RETROSPECTIVE STUDY OF THE LESIONS ASSOCIATED WITH IRON STORAGE DISEASE IN CAPTIVE EGYPTIAN FRUIT BATS (ROUSETTUS AEGYPTIACUS).

Egyptian fruit bats (Rousettus aegyptiacus) are one of many species within zoologic collections that frequently develop iron storage disease. The goals of this retrospective multi-institutional study were to determine the tissue distribution of iron storage in captive adult Egyptian fruit bats and the incidence of intercurrent neoplasia and infection, which may be directly or indirectly related to iron overload. Tissue sections from 83 adult Egyptian fruit bats were histologically evaluated by using tissue sections stained with hematoxylin and eosin, trichrome, and Prussian blue techniques. The liver and spleen consistently had the largest amount of iron, but significant amounts of iron were also detected in the pancreas, kidney, skeletal muscle, and lung. Hepatocellular carcinoma (HCC; 11) was the most common neoplasm, followed by cholangiocarcinoma (4). Extrahepatic neoplasms included bronchioloalveolar adenoma (3), pulmonary carcinosarcoma (1), oral sarcoma (1), renal adenocarcinoma (1), transitional cell carcinoma of the urinary bladder (1), mammary gland adenoma (1), and parathyroid adenoma (1). There were also metastatic neoplasms of undetermined primary origin that included three poorly differentiated carcinomas, a poorly differentiated sarcoma, and a neuroendocrine tumor. Bats with hemochromatosis were significantly more likely to have HCC than bats with hemosiderosis (P = 0.032). Cardiomyopathy was identified in 35/77 bats with evaluable heart tissue, but no direct association was found between cardiac damage and the amount of iron observed within the liver or heart. Hepatic abscesses occurred in multiple bats, although a significant association was not observed between hemochromatosis and bacterial infection. To the authors' knowledge, this is the first publication providing evidence of a positive correlation between hemochromatosis and HCC in any species other than humans.

Dose titration of deferasirox iron chelation therapy by magnetic resonance imaging for chronic iron storage disease in three adult red bald-headed uakari (Cacajao calvus rubicundus).

Iron overload is common in lemurs and some New World nonhuman primates raised in captivity, but there is no such documentation in the red bald-headed uakari (Cacajao calvus rubicundus). This study describes postmortem documentation of severe iron storage disease in one red bald-headed uakari and the use of iron chelation with oral deferasirox in the three surviving members of the colony. Magnetic resonance imaging was used to quantify pretreatment iron burden and to follow the response to therapy in two females, 22 and 28 yr of age, and one male 33 yr of age. Baseline liver iron concentrations ranged from 16 to 23 mg/g dry weight. In humans, a liver iron concentration greater than 15 mg/g is considered severe and associated with endocrine and cardiac toxicity. The uakaris were otherwise asymptomatic, generally healthy, nonpregnant, and on a stable, low-iron diet. Quantitative magnetic resonance imaging indicated that dosage escalations up to 100 mg/kg were needed to produce meaningful reductions in iron stores. After 5 yr of therapy, two animals continue at a dosage of 100 mg/kg per day, and the third was transitioned to twice-weekly maintenance dosing because of successful de-ironing. The animals tolerated iron chelation therapy well, having stable hematologic, renal, and hepatic function profiles before, during, and after treatment. Deferasirox monotherapy may represent a therapeutic option in primates with iron storage disease when dietary measures are ineffective and phlebotomy is logistically challenging.

Deadly outbreak of iron storage disease (ISD) in Italian birds of the family Turdidae.

A widespread deadly outbreak occurred in captive birds belonging to the family Turdidae in Italy. The present study was performed on 46 dead birds coming from 3 small decoy-bird breeders in central Italy. Only Turdus pilaris, Turdus iliacus, Turdus philomelos and Turdus merula were affected. No other species of bird held by these breeders died. A change of diet before the hunting season was reported from all breeders. Full necropsy of the animals and histological investigations of representative tissue samples were performed. Microscopical examination showed marked iron deposits in liver samples. Bacteriological investigations and molecular analysis to exclude bacterial and viral diseases were carried out. Contamination of food pellet samples by mycotoxins and analysis to detect heavy metal contaminants in food pellet samples were considered. An interesting result was the high iron content found in food pellets. It was higher than that considered suitable for birds, especially for species susceptible to development iron storage disease (ISD). Taken together, the results suggested an outbreak of ISD caused by the high iron content of food given to the birds before the hunting season. The high mortality recorded only in species belonging to the family Turdidae suggests a genetic predisposition in the affected birds.

Epistasis in iron metabolism: complex interactions between Cp, Mon1a, and Slc40a1 loci and tissue iron in mice.

Disorders of iron metabolism are among the most common acquired and constitutive diseases. Hemochromatosis has a solid genetic basis and in Northern European populations it is usually associated with homozygosity for the C282Y mutation in the HFE protein. However, the penetrance of this mutation is incomplete and the clinical presentation is highly variable. The rare and common variants identified so far as genetic modifiers of HFE-related hemochromatosis are unable to account for the phenotypic heterogeneity of this disorder. There are wide variations in the basal iron status of common inbred mouse strains, and this diversity may reflect the genetic background of the phenotypic diversity under pathological conditions. We therefore examined the genetic basis of iron homeostasis using quantitative trait loci mapping applied to the HcB-15 recombinant congenic strains for tissue and serum iron indices. Two highly significant QTL containing either the N374S Mon1a mutation or the Ferroportin locus were found to be major determinants in spleen and liver iron loading. Interestingly, when considering possible epistatic interactions, the effects of Mon1a on macrophage iron export are conditioned by the genotype at the Slc40a1 locus. Only mice that are C57BL/10ScSnA homozygous at both loci display a lower spleen iron burden. Furthermore, the liver-iron lowering effect of the N374S Mon1a mutation is observed only in mice that display a nonsense mutation in the Ceruloplasmin (Cp) gene. This study highlights the existence of genetic interactions between Cp, Mon1a, and the Slc40a1 locus in iron metabolism, suggesting that epistasis may be a crucial determinant of the variable biological and clinical presentations in iron disorders.

Iron indices in bottlenose dolphins (Tursiops truncatus).

Bottlenose dolphins can have iron overload (that is, hemochromatosis), and managed populations of dolphins may be more susceptible to this disease than are wild dolphins. Serum iron, total iron-binding capacity (TIBC), transferrin saturation, and ferritin were measured in 181 samples from 141 dolphins in 2 managed collections and 2 free-ranging populations. Although no iron indices increased with age among free-ranging dolphins, ferritin increased with age in managed collections. Dolphins from managed collections had higher iron, ferritin, and transferrin saturation values than did free-ranging dolphins. Dolphins with high serum iron (exceeding 300 µg/dL) were more likely to have elevated ferritin but not ceruloplasmin or haptoglobin, demonstrating that high serum levels of iron are due to a true increase in total body iron. A time-series study of 4 dolphins with hemochromatosis that were treated with phlebotomy demonstrated significant decreases in serum ferritin, iron, and TIBC between pre- and posttreatment samples; transferrin saturation initially fell but returned to prephlebotomy levels by 6 mo after treatment. Compared with those in managed collections, wild dolphins were 15 times more likely to have low serum iron (100 µg/dL or less), and this measure was associated with lower haptoglobin. In conclusion, bottlenose dolphins in managed collections are more likely to have greater iron stores than are free-ranging dolphins. Determining why this situation occurs among some dolphin populations and not others may improve the treatment of hemochromatosis in dolphins and provide clues to causes of nonhereditary hemochromatosis in humans.

Iron storage disease in red deer (Cervus elaphus elaphus) is not associated with mutations in the HFE gene.

Iron storage diseases are rare conditions of dysregulated iron metabolism in man and animals. A genetic basis has been confirmed only for human haemochromatosis. Iron storage disease was diagnosed in six related, 2-year-old male red deer of the same herd. These animals presented with weight loss and rough hair coats. Haematological examination was unremarkable. At necropsy examination, gross lesions were restricted to cachexia. Microscopical examination revealed severe, diffuse hepatocellular necrosis and iron accumulation in hepatocytes, Kupffer cells, cardiac myocytes and renal tubular cells in all affected animals. Four animals also had moderate bridging fibrosis in the liver. Hepatic iron concentrations were increased (1108-2275 mg/kg wet weight; reference range 100-200 mg/kg). Drinking water in rusty iron tubs in the deer park contained eight times more iron than the accepted level for human drinking water. To test for a possible genetic basis of increased iron uptake and storage in red deer, the cervid haemochromatosis gene (HFE) was identified. Sequence comparisons between the six diseased animals and three healthy free-ranging unrelated animals failed to identify differences in the HFE sequences. Furthermore, the disease was not associated with common amino acid substitutions reported in human patients with haemochromatosis, including C282Y and H63D. Polymorphisms in other non-HFE genes involved in iron metabolism may have led to a higher sensitivity to iron and this, together with the high iron content of the drinking water, may have been the cause of the observed iron storage in these red deer.

Effect of tannic acid on iron absorption in straw-colored fruit bats (Eidolon helvum).

Excessive absorption and subsequent storage of dietary iron has been found in a variety of captively held birds and mammals, including fruit bats. It is thought that feeding a diet that is low in iron can prevent the onset of this disease; however, manufacturing a diet with commonly available foodstuffs that contains a sufficiently low iron concentration is difficult. An alternative is to feed captive animals that may be susceptible to this disease potential iron chelators such as tannins that may bind to iron and block its absorption. Using stable isotope methods established in humans, we measured iron bioavailability in straw-colored fruit bats (Eidolon helvum) and tested whether tannic acid significantly reduced the extent of iron absorption. Regardless of dose, tannic acid significantly reduced iron absorption (by 40%) and in the absence of tannic acid, iron absorption was extensive in this species (up to 30%), more so than in humans. Species susceptible to iron storage disease may efficiently absorb iron in the gut regardless of iron status, and supplementing these species with tannic acid in captivity may provide an alternative or additional means of preventing the development of this disease.

High serum concentrations of iron, transferrin saturation and gamma glutamyl transferase in captive black rhinoceroses (Diceros bicornis).

Iron storage disease (haemochromatosis) is thought to be the cause of many disorders unique to captive black rhinoceroses (Diceros bicornis). To establish reliable reference ranges for iron parameters, serum samples from 27 eastern black rhinoceroses (Diceros bicornis michaeli) from a translocation programme in Kenya were analysed and compared with the samples from 17 captive individuals. The transferrin saturation, serum iron concentration and gamma glutamyl transferase were significantly higher in the captive rhinoceroses, but these elevations were not evident when the results were compared with previously published data.

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.

Iron storage disease in captive Egyptian fruit bats (Rousettus aegyptiacus): relationship of blood iron parameters to hepatic iron concentrations and hepatic histopathology.

This study evaluated the relationship between blood iron parameters and hepatic iron concentrations, and correlation of histologic findings with hepatic iron concentrations in a captive population of Egyptian fruit bats (Rousettus aegyptiacus) and island flying foxes (Pteropus hypomelanus). Blood samples were collected for complete blood counts, plasma biochemical profiles, serum iron concentrations, total iron-binding capacity, whole-blood lead concentrations, and plasma ferritin assays. Liver samples obtained by laparotomy were divided, with one half processed for histologic examination and the other half frozen and submitted for tissue mineral analysis. The histologic sections were scored by two blinded observers for iron deposition, necrosis, and fibrosis. The Egyptian fruit bats had significantly higher liver iron (mean = 3,669 +/- 1,823 ppm) and lead (mean = 8.9 +/- 5.8 ppm) concentrations than the island flying foxes (mean [Fe] = 174 +/- 173 ppm, mean [Pb] = 1.9 +/- 0.5 ppm). Hepatic iron concentrations significantly correlated with tissue lead concentrations, histologic grading for iron and necrosis, serum iron, transferrin saturation, and plasma ferritin (P < 0.001). Blood lead concentrations negatively correlated with tissue lead concentrations (P < 0.001). When the product of transferrin saturation and serum iron was greater than 51, an individual animal had a high probability of having iron overload. When the product of these two variables was greater than 90, there was a high probability that the animal had hemochromatosis. On the basis of this study, it appears that evaluation of serum iron, transferrin saturation, and plasma ferritin are useful and noninvasive methods for diagnosis of hemochromatosis in Egyptian fruit bats.

Skeletal changes in hemochromatosis of Salers cattle.

Hemochromatosis is an inherited defect in Salers cattle, characterized by increased iron absorption and wasting in young animals. Loss of teeth and soft bones has been reported. This study details bone changes in a prospective study of an affected Salers heifer and an age-matched, half-sibling control. The heifer fell 2 weeks before euthanasia, developed non-weight bearing lameness, and then became recumbent. At necropsy, the heifer was smaller than the control and had fractures of the humerus, femur, and ribs. Distinctive circumferential laminations in the outer third of the cortex were seen radiographically as layers of variably decreased density. In midshaft cross sections, the cortex was wider in some long bones, and fluorescent labeling revealed irregular and intermittent mineralization in the outer cortical layers. Mineral apposition rates in osteons of the inner cortex were decreased as compared with the control, and longitudinal bone formation at the growth plate was markedly decreased. Histologically, there were buried layers of osteopenic, poorly mineralized plexiform bone in outer circumferential lamellae. There was stainable iron in woven bone cores of the matrix. Iron was found in occasional osteoclasts as well. The mandible was severely affected, with loss of cortical bone as well as trabecular bone around the teeth and resorption of dental roots. Bone analysis revealed iron levels in the affected calf that were 30-50 times greater than the control and decreased percent ash in the outer cortex. These results indicate that periosteal dysplasia and osteopenia are responsible for pathologic fractures and tooth loss.