Glucose phosphate isomerase (GPI) Tadikonda: Characterization of a novel Pro340Ser mutation.

After a thirty-year lag, we serendipitously reestablished contact with a patient with glucose phosphate isomerase deficiency and hydrops fetalis first reported in 1987. We now provide a clinical update and provide results of mutation analysis in this patient, from Southern India. The patient now an adult female of 36 years of age has moderate anemia but requires no transfusions except with some intercurrent illnesses. Exome sequencing studies showed a homozygous c.1018C>T (Pro340Ser) mutation in exon 12 of the glucose phosphate isomerase gene and later confirmed by direct sequencing. This mutation has not been previously described. To our knowledge, this is also the first known homozygous mutation in the hydrophobic core of the protein and is a highly deleterious mutation by in silico analysis and by clinical history in the family. Flow cytometry studies of band 3 content with eosin maleimide showed a unique tail of red cells on histograms, reflecting the dense red cells (presumably ATP depleted) seen on blood smears; similar findings were seen in patients with pyruvate kinase and phosphoglycerate kinase deficiency.

Iron storage disorders in captive wild mammals: the comparative evidence.

Excessive burden of iron, or iron storage disease (ISD), has been reported in a large variety of captive mammal species, including browsing rhinoceroses; tapirs; fruit bats; lemurs; marmosets and some other primates; sugar gliders; hyraxes; some rodents and lagomorphs; dolphins; and some carnivores; including procyonids and pinnipeds. This report collates the comparative evidence for species' susceptibility, recognizing that the data for mammal species are limited. Differences reported in the occurrence of ISD between facilities, or within facilities over periods that span management changes, have been reported in individual cases but are underused in ISD research. Given the species composition, the hypothesis that evolutionary adaptations to the iron content and availability in the natural diet determine a species' susceptibility to ISD (in the face of deviating iron content and availability in diets offered in captivity) seems plausible in many cases. But exceptions, and additional species putatively susceptible based on this rationale, should be investigated. Whereas screening for ISD should be routine in zoo animal necropsy, screening of live individuals may be implemented for valuable species, to decide on therapeutic measures such as chelator application or phlebotomy. Whatever the reasons for ISD susceptibility, reducing dietary iron levels to maintenance requirements of the species in question seems to be a logical, preventive measure.

Browse diversity and iron loading in captive sumatran rhinoceroses (Dicerorhinus sumatrensis): a comparison of sanctuary and zoological populations.

Iron storage disease (ISD) is now recognized as a serious clinical disorder acquired by two species of browsing rhinoceroses, the African black (Diceros bicornis) and the Asian Sumatran (Dicerorhinus sumatrensis) rhinoceroses, when displaced from their natural habitats. The most complete knowledge of ISD comes from studies of the black rhinoceros, but the Asian species is also at risk. Sumatran rhinoceroses housed in traditional zoological settings outside of range countries have suffered significant morbidity and mortality potentially related to ISD induced by diet and/or other confinement conditions. With so few animals in captivity, very little information exists on iron loading in the Sumatran rhinoceros. To better characterize the problem, we retrospectively compared captive management conditions of Sumatran rhinoceroses housed under traditional zoological care with those in two native sanctuary environments. In general, zoo rhinoceroses are offered a paucity of plants and browse species compared with their sanctuary and wild counterparts managed in native rainforest habitats. Iron analyte levels and limited histopathologic observations in these populations suggest variable tendencies to overload iron, dependent upon differences in managed diet and individual food preferences. More detailed investigation of these markedly dissimilar ex situ populations is warranted to better understand the role of nutrition and other conditions affecting iron loading in browser rhinoceroses.

Review of laboratory and necropsy evidence for iron storage disease acquired by browser rhinoceroses.

Necropsies of two browser rhinoceroses, African black (Diceros bicornis) and Sumatran (Dicerorhinus sumatrensis), often reveal extensive iron-pigment deposition in various tissues. This condition (hemosiderosis) has not been observed in species that are natural grazers, African white (Ceratotherium simum) and Asian greater one-horned (Indian; Rhinoceros unicornis), nor in any species free ranging in the wild. The causes, clinical significance, and consequences of captivity-acquired hemosiderosis have remained controversial despite two decades of compelling evidence that iron tends to accumulate logarithmically in all members of affected species in proportion to periods of expatriation; total-body iron loads can reach 10-fold in less than 3 yr and eventually exceed reference ranges by two to three orders of magnitude; iron overburdens are accompanied by laboratory and histopathologic evidence of cellular injury, necrosis and other clinical consequences characteristic of chronic pathologic iron storage [corrected] disorders (ISD) in humans and other species (hemochromatosis); and that ISD develops in many other exotic wildlife species displaced from their natural habitats. The historical evolution of evidence establishing the development of pathologic ISD in browser (but not in grazer) rhinoceroses and the possible relevance of ISD to other conditions affecting these two species will be reviewed. Evidence reviewed includes new as well as published data derived from quantitative measurements of iron analytes in sera and necropsy tissues and histopathologic evaluations of current and past necropsies of captive and free-ranging rhinoceroses of all four available species. The evolutionary, husbandry, and conservation implications of ISD in rhinoceroses are relevant to understanding ISD acquired by many other species of exotic wildlife when displaced from their natural environments.

Atypical hematological response to combined calorie restriction and chronic hypoxia in Biosphere 2 crew: a possible link to latent features of hibernation capacity.

Eight humans were isolated for 2 years in Biosphere 2, a sealed airtight habitat with recycled air, food, water, and wastes. A combination of conditions led to selective decline of oxygen (O2) in the internal atmosphere from 21% to 14%, inducing symptoms of high-altitude sickness but with little or no compensatory increase in red cell production. All crew members exhibited significant decreases in both erythrocyte 2,3-bisphosphoglycerate (2,3-BPG) concentrations and P50 [partial pressure of O2 for 50% hemoglobin (Hb) saturation] values, changes opposite those expected in adaptation to high-altitude hypoxia. Lower P50 with increased Hb-O2 affinity induced by low 2,3-BPG is a characteristic of hibernating species and could be advantageous in O2-impoverished environments. The mechanisms underlying these changes in the Biosphere 2 crew remain obscure but could be related to low-calorie diet (1750-2100 kcal/day). Because the combination of hypoxia and limited caloric intake is also characteristic of hibernation, this unusual response may represent a cross-adaptation phenomenon in which certain features of hibernation capability are expressed in humans.