Subject(s)
Copper/metabolism , Dog Diseases/diagnosis , Fanconi Syndrome/veterinary , Liver Diseases/veterinary , Metal Metabolism, Inborn Errors/veterinary , Animals , Chelation Therapy/veterinary , Chemical and Drug Induced Liver Injury , Dog Diseases/chemically induced , Dog Diseases/therapy , Dogs , Fanconi Syndrome/diagnosis , Fanconi Syndrome/therapy , Kidney/pathology , Liver/pathology , Liver Diseases/diagnosis , Male , Metal Metabolism, Inborn Errors/diagnosis , Metal Metabolism, Inborn Errors/therapyABSTRACT
A 9-year-old Bedlington Terrier was evaluated because of weight loss, inappetence, and hematemesis. Copper storage disease had been diagnosed previously on the basis of high hepatic copper concentration. Treatment had included dietary copper restriction and administration of trientine for chelation of copper. A CBC revealed microcytic hypochromic anemia. High serum activities of liver enzymes, high bile acid concentrations, and low BUN and albumin concentrations were detected. Vomiting resolved temporarily with treatment, but the clinicopathologic abnormalities persisted. Results of transcolonic portal scintigraphy suggested an abnormal shunt fraction. Results of liver biopsy and copper quantification revealed glycogen accumulation and extremely low hepatic copper concentration. Serum and hair copper concentrations were also low. Chelation and dietary copper restriction were tapered and discontinued. Clinical signs and all clinicopathologic abnormalities improved during a period of several months.
Subject(s)
Chelating Agents/adverse effects , Chelation Therapy/veterinary , Copper/deficiency , Dog Diseases/etiology , Metal Metabolism, Inborn Errors/veterinary , Trientine/adverse effects , Animals , Chelating Agents/therapeutic use , Chelation Therapy/adverse effects , Copper/administration & dosage , Copper/metabolism , Diet/adverse effects , Diet/veterinary , Dog Diseases/diet therapy , Dog Diseases/drug therapy , Dogs , Iatrogenic Disease/veterinary , Liver/chemistry , Male , Metal Metabolism, Inborn Errors/diet therapy , Metal Metabolism, Inborn Errors/drug therapy , Time Factors , Trientine/therapeutic useABSTRACT
Lethal-milk (lm), a recessive mutation, occurred in the C57BL/6J inbred strain of mice. Lactating lm dams produce a zinc-deficient milk that is lethal to all nursing pups. If foster-nursed on normal dams, lm pups survive and become reproductively mature. Injection of zinc-glycinate into the pups or zinc supplementation of the water of the lactating dams reduces lethality. Other pleiotropic effects in lm mice include congenital otolith defects with delayed righting, "tail-spinning," and abnormal swimming. These effects are diagnostic criteria for segregation of lm mice among backcross progeny. About 40 percent of the expected number of lm pups survive to weaning. Zinc supplementation of the dam improves development of saccular but not of utricular otoliths; zinc does not improve survival of the lm pups among backcross progenies. The lm mice over eight months of age also exhibit extensive hair loss, dermatitis, and skin lesions. Possible roles of metallothionein in zinc and copper metabolism are discussed in regard to the pleiotropic effects of the lethal-milk mutation.
Subject(s)
Metal Metabolism, Inborn Errors/veterinary , Mice, Mutant Strains/metabolism , Milk/metabolism , Otolithic Membrane/abnormalities , Rodent Diseases/metabolism , Saccule and Utricle/abnormalities , Zinc/metabolism , Age Factors , Animals , Animals, Suckling , Female , Lactation , Male , Metal Metabolism, Inborn Errors/metabolism , Metallothionein/analysis , Mice , Mice, Mutant Strains/genetics , Pregnancy , Zinc/administration & dosage , Zinc/deficiencyABSTRACT
Deficiency of dietary Zn rapidly reduces both appetite and growth, the latter effect being apparently caused by a failure of cell replication. Diagnosis of presymptomatic Zn deficiency depends largely on estimation of plasma Zn concentration but is complicated by reductions of it during a range of stressful conditions. In the latter cases, the decrease in plasma Zn concentration does not appear to be associated with inadequate Zn intake. Only two genetic defects of Zn metabolism are known in animals. One is associated with lethally inadequate concentrations of Zn in the milk of mice, the other with the A46 trait in Friesian cattle. A46 is a recessively inherited defect of Zn absorption which is lethal in the absence of major Zn supplementation of the diet. The characteristics of the disease are very similar to those of acrodermatitis enteropathica in man.