Evaluation of adenosine deaminase and other purine salvage pathway enzymes in horses with combined immunodeficiency

Abstract

Foals with combined immunodeficiency had normal levels of purine salvage pathway enzymes, including adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase.Functional studies of primary immunodeficiency disorders have increased our understanding of these conditions, but have not provided a molecular basis for the disorders. In one syndrome, severe combined immunodeficiency (CID), approximately half of the children examined lacked adenosine deaminase (ADA), which converts adenosine to inosine in a purine salvage pathway (reviewed in references 12 and 14). Most CID children with ADA deficiency had an autosomal recessive mode of inheritance, whereas normal ADA levels were associated with sex-linked CID (3,5,6,(12)(13)(14)(15).CID in young horses is similar to severe CID of children (9-11). Affected foals have lymphopenia, absence of serum immunoglobulin M, decrease of B lymphocytes, absence of specific antibody response to challenge, decreased lymphocyte proliferation to phytolectins, absence of organized lymphoid structures in the spleen and lymph nodes, and thymic hypoplasia. Af-fected foals die before 4 to 5 months of age from a variety of infectious diseases, notably, though not exclusively, adenoviral and Pneumocystis carinii pneumonias. The defect occurs in Arabian and part-Arabian foals and appears to be inherited as an autosomal recessive trait. We felt it was important to determine whether ADA deficiency or deficiency of other enzymes (nucleoside phosphorylase [NPI or xanthine oxidase [XO]) of the same purine salvage pathway was associated with CID in foals.Tissue (4), erythrocyte, lymphocyte (2), and platelet preparations were prepared from five CID foals (four males and one female) and five normal foals. Lymphocyte counts in the five CID foals ranged from 76 to 580/m3, whereas the normal range was 1,150 to 8,570/mm'. ADA was measured by adenosine conversion to inosine by recording the decrease in optical density at 265 nm (8). Another ADA assay was a coupled reaction requiring the addition of 70 ,ug of TABLE 1. Amounts of ADA in tissues from normal and CID foals CID Normal Tissue No. exam-M No. examined Mean Range ined Mean Range Lymph node 5 93" 43-153

Reference values for amino acids and acylcarnitines in peripheral blood in Quarter horses and American Miniature horses

“…Reference ranges for these compounds have been established for obese rats, adult canines and even for plants by tandem mass spectrometry (MS/MS) [ 3 – 5 ] and atypical myopathies have been identified in horses ( Equus caballus ) using this technology [ 6 ]. Metabolic disorders are common in horses, and can be categorized as disorders of carbohydrate metabolism [ 7 ], lipid disorders [ 8 ], purine disorders [ 9 ], and primary disorders of electrolytic flux [ 10 ]. Diet [ 11 ] and metabolic disorders are important factors affecting amino acid and acylcarnitine concentrations in horses [ 12 ].…”