Acute episodic hemolysis in the African black rhinoceros as an analogue of human glucose‐6‐phosphate dehydrogenase deficiency

Abstract

Sudden episodes of massive hemolysis have become the most common cause of death among captive black rhinoceroses, and there is evidence that they occur in the wild as well. We have observed radically unique enzyme and metabolite profiles in normal rhinoceros erythrocytes compared to humans and other mammals, including marked deficiencies of intracellular adenosine triphosphate (ATP), catalase, adenosine deaminase, and other enzymes involved in glycolysis, glutathione cycling, and nucleotide metabolism. Minimal concentrations of ATP appear to impair effective acceleration of hexosemonophosphate shunt activity in response to oxidants by restricting substrate generation at the hexokinase step. Antioxidant defenses are further compromised by catalase deficiency, which may be a general characteristic of rhinoceros erythrocytes, perhaps related to the common occurrence of severe mucocutaneous ulcerative disease. It is proposed that erythrocyte ATP deficiency in rhinoceroses may be an evolutionary adaptation conferring selective advantage against common hemic parasites, comparable to the role of human glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in falciparum malaria.

Increased inflammation and decreased insulin sensitivity indicate metabolic disturbances in zoo-managed compared to free-ranging black rhinoceros (Diceros bicornis)

“…The worldwide ex situ population of $250 black rhinos (Emslie, 2012) also is under threat, chiefly due to a unique vulnerability to unusual disease syndromes. These maladies include hemolytic anemia (Miller and Boever, 1982;Paglia, 1993;Paglia et al, 1986), rhabdomyolysis (Murray et al, 2000), hepatopathy (Paglia and Tsu, 2012) and ulcerative skin disease (Munson et al, 1998), which contribute to morbidity and mortality (Carlstead et al, 1999;Dennis, 2004;Dennis et al, 2007). Iron overload, or hemosiderosis, is one of the most commonly reported conditions, commonly diagnosed by measuring serum ferritin and iron, total iron binding capacity and transferrin saturation (Kock et al, 1992).…”

Babesia bicornis sp. nov. and Theileria bicornis sp. nov.: Tick-Borne Parasites Associated with Mortality in the Black Rhinoceros ( Diceros bicornis )

“…However, the rhinoceroses Bahati (case 1) and Maggie (case 2) did not die in captivity and had been translocated to the Ngorongoro Conservation Area in Tanzania several years earlier. Other causes of anemia in black rhinoceroses, such as leptospirosis (8), trypanosomiasis (7), and autoimmune disorders (9), have also been described and should therefore be taken into account in any differential diagnosis (11,12). As far as other tick-borne diseases are concerned, serological evidence for exposure of black and white rhinoceroses to heartwater disease, transmitted by Amblyomma ticks, has been reported from Zimbabwe (5).…”

Red blood cell metabolism shows major anomalies in Rhinocerotidae and Equidae, suggesting a novel role in general antioxidant metabolism

“…These results leave a number of unresolved problems, including (1) how does tyrosine accumulate in rhinoceros red cells?, (2) what is the physiological role of heme with respect to oxidant production or removal?, (3) what is the explanation for the unusual dynamics of red cell urate production and destruction, and (4) do levels of red cell tyrosine, urate (and ORAC) vary under different dietary or exercise regimes, or in response to antioxidant treatments?…”

“…We have also demonstrated diminished erythrocyte glycolysis through the hexose monophosphate shunt [4], and this, together with the presence of Heinz bodies in erythrocytes of normal individual rhinoceroses [2], suggests that impairments in antioxidant capacity may contribute to the hemolytic tendency.…”

“…Despite extensive haematological investigation [1], the causes of this remained uncertain. However, the black rhinoceros does show some striking peculiarities in respect to its normal red cell biochemistry: many enzyme activities are very different, catalase especially being only about 2% of levels in human red cells, and ATP levels are remarkably low relative to other mammals [2,3].…”