Patient with Lesch Nyhan disease

The patient, a 29-month-old boy with severe Lesch-Nyhan disease (HPRT activity less than 3 pmol inositic acid/mg protein/h) was withdrawn from allopurinol therapy over 5 days. Blood and urine were obtained at 0830 h and 1630 h. After baseline studies for 3 days, the patient was treated with 100 U of XOD artificial cells via a nasogastric tube twice a day (0900 and 1200 h) for 10 days. A sample of his cerebrospinal fluid was obtained at 1630 h before treatment and on the final day of therapy.

Purines were measured by high-performance liquid chromatography and uric acid and creatinine were measured enzymatically and colorimetrically, respectively.

After withdrawal of the allopurinol, uric acid excretion rose rapidly; baseline uric acid/creatinine ratios at 0900h ranged between 3.5

UA: uric acid HX: hypoxanthine INO: inosine XAN: Xanthine

Before

After 10 days of oral enzyme artificial cells

Fig. 6.7. Effect of oral XOD artificial cells on cerebral spinal fluid concentrations of uric acid, hypoxanthine, inosine and xanthine (modified from Palmour et a/., 1989).

and 4.1. With the introduction of XOD artificial cells, the morning and afternoon ratios fell to normal within 3 days. During a febrile episode of otitis media the ratios rose transiently. Urinary hypoxanthine excretion also responded promptly to the XOD treatment, the pattern of transient escape during the febrile illness being repeated. The CSF hypoxanthine levels fell by 25% after 10 days of XOD artificial cell administration (Fig. 6.7) and the CSF inosine levels fell by 32% (380 to 260 ng/ml). The levels of CSF xanthine and uric acid, both normal, remained unchanged.

The effect of XOD on plasma inosine was rapid (Fig. 6.8) and within 3 days, the plasma inosine levels had fallen to below 5 ^g/ml. There was a reduction in plasma xanthine levels after day 6. The hypoxanthine levels manifested wide diurnal fluctuations but a regression line indicated a gradual decrease.

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Musiknoten Zum Ausmalen

_Pre Px 1 Oral xanthine oxidase artificial cells (days) 10

start

Fig. 6.8. Plasma xanthine and inosine levels before and after administration of oral XOD artificial cells on day 1 shown as "start" in the figure. Hypoxanthine levels, not shown here, manifest wide diurnal fluctuations but a regression line indicates a gradual decrease (modified from Palmour etal.; Chang, 1989).

_Pre Px 1 Oral xanthine oxidase artificial cells (days) 10

start

Fig. 6.8. Plasma xanthine and inosine levels before and after administration of oral XOD artificial cells on day 1 shown as "start" in the figure. Hypoxanthine levels, not shown here, manifest wide diurnal fluctuations but a regression line indicates a gradual decrease (modified from Palmour etal.; Chang, 1989).

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