Congenital dyserythropoietic anaemia and dyskeratosis in Australian Poll Hereford calves.

Congenital dyserythropoietic anaemia (CDA) is a heterogeneous group of rare genetic disorders that in humans is characterised by ineffective haematopoiesis with morphological abnormalities in erythroid precursor cells and secondary iron overload. In the 1990s, a syndrome of CDA with dyskeratosis and progressive alopecia was reported in Poll Hereford calves in Canada and the USA. We report the clinical and pathological findings in two Poll Hereford calves with this syndrome from separate properties in South Australia. The animals had a variably severe anaemia, associated with abnormal nucleated red blood cells in peripheral blood, and large numbers of rubricytes and metarubricytes with a characteristic nuclear ultrastructure in the bone marrow. Both calves were born with a wiry hair coat and a progressively 'dirty-faced' appearance associated with hyperkeratosis and dyskeratosis (apoptosis).

Epidemiologic findings in congenital anemia, dyserythropoiesis, and dyskeratosis in polled Hereford calves.

Congenital dyserythropoiesis and dyskeratosis occur within certain lines of Polled Hereford cattle. Eighty-nine of 90 alleles in 45 affected calves had a mechanism in which they could be identical by descent from an identified common ancestor. The line allele may have been a recurrence of the mutation, or the mutation may have occurred earlier in the breed's history and been distributed throughout the breed by the extensive use of several ancestors. No evidence of disease has been identified in sire and dams of affected calves, suggesting that the allele is not acting in a dominant or incompletely dominant manner. Even distribution of cases between sexes suggests that the disease is not sex linked or sex influenced. A higher degree of inbreeding in the affected calves and temporal and spatial features that separated individual cases also suggest a genetic cause. Segregation ratios were not significantly different from those of the hypothesized simple autosomal recessive inheritance.

Ultrastructural findings in congenital anemia, dyskeratosis, and progressive alopecia in Polled Hereford calves.

Ultrastructural evidence of dyserythropoiesis was found in ten calves (ages 1 to 16 months) previously diagnosed as having congenital anemia, dyskeratosis, and progressive alopecia. Morphologic abnormalities found in erythroid precursors of all calves were associated with the nucleus. Rubriblast nuclei were irregular with numerous blebs, indentations, and deep clefts. Elongated blebs appeared as satellite nuclei in some sections. Nuclear membranes had numerous defects or gaps, which were frequently present in, but not limited to, recently divided cells. Cytoplasmic material could be found within these gaps and extending into the nucleus. Rubricytes had chromatin that was abnormally condensed and hyperosmiophilic, with numerous translucent vacuoles present. Binucleate rubricytes occurred frequently in affected calves. These changes resemble those of type I congenital dyserythropoiesis in human beings, and we suggest congenital anemia, dyskeratosis, and progressive alopecia of Polled Hereford calves as the appropriate diagnostic terms to describe this disease.

Congenital dyserythropoiesis and progressive alopecia in Polled Hereford calves: hematologic, biochemical, bone marrow cytologic, electrophoretic, and flow cytometric findings.

Congenital dyserythropoiesis with dyskeratosis is a slow, progressive, and often fatal disease in Polled Hereford calves. Affected calves have a macrocytic normochromic anemia with a mild reticulocytosis. Studies indicate that calves are hyperferremic with increased saturation of serum total iron binding capacity, which rules out iron deficiency as a cause. Other secondary causes of dyserythropoiesis, including cobalamin and folate deficiencies, are unlikely because serum cobalamin and folate levels of affected calves were normal. Virus isolation was negative, and failure to identify bovine retroviral antigens or antibodies from several calves suggested that viral agents were not involved. Bone marrow cytologic findings were similar to those in congenital hereditary dyserythropoiesis in humans and included occasional multinucleate cells, internuclear chromatin bridging between nuclei of partially divided cells, and, more frequently, irregular nuclear shapes and chromatin patterns. DNA content and cell cycle distribution of erythroid cells appeared normal, and no electrophoretic abnormalities were detected in erythrocyte membrane proteins. The Polled Hereford syndrome is similar in many ways to type I congenital dyserythropoiesis in humans and may be an appropriate biomedical model for studying erythroid proliferation during dyserythropoiesis.

Dyserythropoiesis, polymyopathy, and cardiac disease in three related English springer spaniels.

A polysystemic disorder was observed in three related English Springer Spaniel dogs that demonstrated regurgitation from an early age, slowly progressive temporal muscle atrophy with partial trismus, and less pronounced generalized skeletal muscle atrophy. All dogs exhibited moderate dyserythropoietic anemia, polymyopathy with megaesophagus, and varying degrees of cardiomegaly. The prevalence, etiology, underlying pathomechanism, and possible mode of inheritance remain to be elucidated.