Zinc Deficiency-Like Syndrome in Fleckvieh Calves: Clinical and Pathological Findings and Differentiation from Bovine Hereditary Zinc Deficiency

Langenmayer, M.C.; Jung, S.; Majzoub-Altweck, M.; Trefz, F.M.; Seifert, C.; Knubben-Schweizer, G.; Fries, R.; Hermanns, W.; Gollnick, N.S.

The predominantly mild microcytic, normochromic anemia, and mild hypoalbuminemia of the calves is very likely because of the chronic inflammatory state. 15-17 Leukocytosis reflects the severe inflammatory infiltration in skin, respiratory, or digestive tract. Decreased serum zinc concentrations can be associated with chronic inflammation as well. Additionally, the chronic enteritis and the catabolic state of the calves could be the cause of hypoalbuminemia. The concentrations of the trace elements copper and iron were below reference ranges in 3/7 and 4/5 calves, respectively. The low iron concentrations can be caused by the chronic inflammatory state or reduced alimentary uptake because of disease-associated anorexia. However, the causes and connections of the metabolic disturbances in these calves are not known. As copper, iron, and zinc concentrations also have synergistic and antagonistic properties in physiological states, the reason for the observed concentration changes in this disease deserves further study. The similarity of the ZDL phenotype to BHZD is striking, even though the genetic cause and affected breeds are clearly distinct. 2, 3 Bovine hereditary zinc deficiency, first described in Holstein Friesian calves, 1 affects a variety of cattle breeds including Fleckvieh, Holstein Friesian, Shorthorn, and Angus. 8, 18, 19 Bovine hereditary zinc deficiency-affected calves show keratinization disorders, thymus hypoplasia, respiratory and digestive tract inflammations, oral mucosal ulcerations, impaired function of the immune system, and growth retardation as consequence of a malfunction of an intestinal zinc transporter. [20] [21] [22] In zinc deficiency in Holstein Friesian cattle, a splice-site variant in the SLC39A4 gene is the underlying mutation. 2 This gene encodes a zinc transporter which is crucial for intestinal zinc uptake. 23 In humans, several additional mutations in this gene are also responsible for an inherited zinc deficiency syndrome known as acrodermatitis enteropathica. [24] [25] [26] Because of the malfunction of the intestinal zinc transporter, BHZD calves do respond to oral zinc supplementation. 20, 27 In one study, clinical signs developed when plasma zinc concentration dropped below 0.5 ppm and a plasma zinc concentration of 1.0 ppm was maintained through oral supplementation to keep the animal without clinical signs. 27 In the present study, the zinc doses were within (Calf 2) and above (Calf 4) the range of published values used to alleviate or resolve clinical disease of zinc deficient calves. 8, 20, 27 In both calves, serum zinc concentrations responded to the treatment and were above the maintenance zinc concentrations of Machen et al. 27 Unfortunately, the exact dose given to Calf 6 is not known, however, serum zinc concentration was at the upper limit of the reference range and was also above the maintenance zinc concentration of Machen et al. Calf 9 was treated with 10-16 mg elementary zinc per day. This dose appears really low when compared to the other calves and its effects were probably minor (low serum zinc concentrations). Although serum zinc concentrations are not always useful to determine tissue zinc concentrations, 28 elevation after treatment indicates that intestinal uptake took place. In zinc-treated BHZD calves, clinical signs improve after 1-3 weeks and completely resolve after 2-6 weeks. 2, 20 However, the clinical signs observed in Calves 2, 4, and 6 did neither improve nor resol