Copper deficiency in puppies: case report and review of literature

Introduction : Copper (Cu) is an essential nutrient readily absorbed in the stomach and duodenum via Ctr1 membrane transport protein (Lindblad-Toh et al. 2005. Nature 438 (7069): 803–819), carried bound to metallochaperons for predominantly hepatic storage, and excreted via bile. Cu is a critical cofactor of several cuproenzymes, catalyzing electron transfer reactions required for iron oxidation, cellular respiration, pigment formation, peptide amidation, connective tissue formation, neurotransmitter biosynthesis, and antioxidant defense (Balamurugana and Schaffner. 2006. Biochim Biophys Acta 1763:737–746). Hepatic Cu stores are easily depleted when Cu intake is impaired by dietary Cu deficiency or malabsorption (Zentek and Meyer. 1991. J Nutr. 1991 Nov; 121(11 Suppl):S83-4), especially at times of high energy demand of growth, reproduction, or recovery. Loss of transporters or cuproenzymes’ function accounts for most clinical signs of Cu deficiency. Animals, Materials, and Methods : A 6 year old Flatcoated Retriever and her 2-month old puppies were presented due to abnormal coat color at birth in 6 out of 8 puppies. For the duration of pregnancy, the female was fed natural Pet’s Planet Timmy and Active (Nieve, Italy) adult complete diets ad libitum. The Pet’s Planet Joy, a complete adult diet for small breeds, was used during lactation and to wean the puppies, then switched to a growth formula, Eukanuba Puppy Growth (Procter & Gamble) a week before presentation. Analyses of Cu and Zn content in serum and urine were performed in two puppies and the lactating female, in addition to physical exam, complete blood count (CBC), standard biochemistry panel (Chem), complete urinalysis, and microscopic examination of the hair shafts. The absolute intake of Cu, Ca, Zn and Fe by the female, and the mineral availability to puppies were estimated. Results and Discussion : Gestation, parturition, and lactation were uneventful. There was no history of diarrhea, all were dewormed, their growth and activity were normal. Lactating female was fed adult rather than growth formula, and although all three diets were supplemented with Cu sulfate pentahydrate, the resulting Cu intake was only 50% of NRC recommended 1.52mg/kg0.75 at peak lactation. Physical exam of the puppies was unremarkable except for symmetrical bilateral aberration in coat quality and color. The most affected puppy was the largest and had a grey discoloration extending from the cranial thorax to the tip of the tail, encompassing entire dorsum as well as the lateral aspects of the trunk and legs. Other puppies had prominent discoloration at the tail and caudal aspect of the thighs. All animals had dry and dull coat, with severity being proportional to the degree of discoloration. Microscopic examination of the hair shafts revealed lack of pigment granules in the cortex of the hair shaft, a defect in eumelanin melanogenesis. Generalized leukotrichia due to malnutrition was diagnosed. CBC and Chem were normal with exception of normocytic hypochromic anemia, anisocytosis, and hypocupremia of 6.12 and 6.91 µmol/L in the puppies and 7.54 µmol/L in the female (normal 10.99-21.98 µmol/L). Serum Zn, Ca, and P were within normal levels, while Fe, ceruloplasmin and cobalamin were not measured. Urinalysis did not show cupriuresis nor increased excretion of Zn. Conclusions : As a result of inadequate dietary Cu intake in time of high energy demand of growth and lactation, we observed the principal features of Cu deficiency: blood changes consistent with effects of Cu deficiency on erythropoiesis, hypocupremia, and leukotrichia. Radiographic examination should have been conducted to evaluate for presence of skeletal abnormalities common with Cu deficiency such as osteoporosis. Within a week of dietary intervention coat returned to normal pigmentation at the epidermal aspect of the hair shafts. Feeding life stage appropriate diet and close monitoring of mineral balance in designing growth and recovery diets remains crucial to avoid deficiencies and oversupplementation