Deficient Children

UNINTENDED CDNSEQUENCES OF GENE THERAPY Immune Deficient Children 

In 2000, French researchers announced the first gene therapy cure in nine children with X-linked severe combined immune deficiency (X-SCID). This rare condition is caused by the inherited loss of a protein that is part of the docking site for critical immune system signal proteins. Because of this defect, children with X-SCID have no mature, working lymphocytes—critical immune system cells. 

As a result, they are so susceptible to viral and bacterial infections that they rarely survive infancy. In the French scientists research, blood stem cells were removed from an affected child, treated with a retroviral vector carrying a normal docking protein gene, and returned to the child. Nine out of ten children treated in this way developed functional, mature immune system cells, which provided them with protection against infections. News articles proclaimed that a cure had been found. 

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The antibody response to yellow fever vaccine was impaired in protein-deficient children with kwashiorkor compared to the well-nourished controls. Polio antibody production was normal in the malnourished children, all of whom also responded in the normal fashion to smallpox vaccination. They had no evidence of disseminated vaccinia (B8). In Guatemala, on the other hand, smallpox vaccination of children who had fully recovered from severe protein-calorie malnutrition led to a drop in their nitrogen retention with the added complication of disseminated vaccinia (V3). 

Vitamin A deficiency is worldwide one of the most prevalent nutrition-dependent deficiency diseases. It leads to changes of the respiratory epithelium, which result in repeated infections of the respiratory tract, the main cause of death in vitamin A-deficient children. The difficulty in supplying the respiratory epithelium with vitamin A is that the affected children frequently suffer as well from infections of the gastrointestinal tract with subsequent reduction of the absorption of fat-soluble vitamins. Nutritargeting can in these cases avoid the problems of malabsorption and ensure the micronutrient supply. 

Kaplan, S.L., L.E. Underwood, G.P August, J.J. Bell, S.L. Blethen, R.M. Blizzard, D.R. Brown, T.P Foley, R.L. Hintz, N.J. Hopwood, et al.. Clinical studies with recombinant-DNA-derived methionyl human growth hormone in growth hormone deficient children. Lancet, 1986.1(8483) 697-700. 

Thyroid function tests are often altered by somatropin because of increased conversion of T4 to T3, but this is clinically insignificant at low doses (SEDA-21, 453). One child with Prader-Willi syndrome had a fall in serum thyroxine concentration during somatropin therapy and needed thyroxine replacement (33). Hypothyroidism developed in 11 of 46 growth hormone-deficient children treated with somatropin (34). Prior abnormalities in hypothalamic-pituitary function and alterations in thyroid hormone metabolism, probably both, contributed to the high incidence of hypothyroidism, which was similar to that in previous studies. 

Crepaz R, Pitscheider W, Radetti G, Paganini C, Gentili L, Morini G, Braito E, Mengarda G. Cardiovascular effects of high-dose growth hormone treatment in growth hormone-deficient children. Pediatr Cardiol 1995 16(5) 223-7. 

The evidence for a pterin-substituted 1,2-enedithiolate was first reported by Raja-gopalan, Johnson, and coworkers, who isolated pterins from the oxidative decomposition of molybdenum-bound MPT, Figure 4 [7,49,55,56], In complementary work, Taylor and coworkers confirmed the structure of several of the pterin decomposition products by direct synthesis (see Section V. A) [30,57-59], Urothi-one, first isolated in 1940 from human urine [60], was shown to be a metabolic degradation product of MPT [37], Other isolated pterin-containing decomposition and/or derivatized products from molybdenum enzymes include Form A, Form B (a urothione-like product), and camMPT (Figure 4) [7], Two other pterins, Form Z and the MPT precursor, can be obtained from molybdenum deprived organisms, N. crassa Nit-1, and oxidase-deficient children, neither of which pro-... 

Growth hormone 16 Evaluate Abs in children treated with rh-GH and met-GH 46 GH-deficient children treated for at least 12 months (20 naive and 26 previous treatment with pituitary extracted GH) RIA Abs generated in 75% of treatment naive group within 1 year 12% of the pretreated group (only in the second year). Abs remained through duration of treatment with met-GH, but decreased and eventually become undetectable in subjects receiving rh-GH. Abs did not affect clinical efficacy... 

Massa G,Vanderschueren-Lodeweyckx M, Bouillon R Five year follow up of growth hormone antibodies in growth hormone deficient children treated with recombinant human growth hormone. Clin. Endocrinol. (1993) 38(2) 137-142. 

Rougeot C, Marchand P, Dray F, Girard F, Job JC, Pierson M, et al. Comparative study of biosynthetic growth hormone immunogenicity in growth hormone deficient children. Hormone Res. (1991) 35(2) 78-81. 

Plasma Retinol Binding Protein Measurement of plasma concentrations of RBP may give some additional information. Indeed, it has been suggested that because retinol is susceptible to oxidation on storage of blood samples, measurement of RBP may be a better indication of the state of vitamin A status. In adequately nourished subjects, about 13% of immunologi-caUy reactive RBP in plasma is present as the apo-protein, whereas in vitamin A-deficient children, the proportion of apo-protein may rise to 50% to 90% of... 

Melon T, Forteleoni G, Ogana A, Franca V. Aspirin-induced acute haemolytic anaemia in glucose-6-phosphate dehydrogenase-deficient children with systemic arthritis. Acta Haematol 1989 81(4) 208-9. 

GH has been recognixed as an effective replacement therapy for GH-deficient children. The supply of GH. however, was very limited because its source was the pituitary glands of human cadavers, and several reports of deaths in children with Creut/fcldt-Jakob disease (caused by viral contamination of GH) baited the di.stribution of GH in 1977. Both of these problems were. solved with the application of rDNA technology in the commercial production of somatrem and snmatmpin. 

Sveger T. The natural history of liver disease in alpha 1-antitrypsin deficient children. Acta Paediatr Scand 1988 77 847-51. 

Blethen SL, Bapitista J, Kuntze J, et al. Adult height in growth hormone (GH)-deficient children treated with biosynthetic GH. J Clin Endocrinol Metab 1997 82 418 20. 

PirazzoU P, Cacciari E, Mandini M, et al. Eollow-up of antibodies to growth hormone in 210 growth hormone-deficient children treated with different commercial preparations. Acta Paediatr 1995 84 1233-1236. 

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