Neopterin: biopterin ratios in Down's syndrome


Journal of Neurology, Neurosurgery and Psychiatry 1989;52:1015-1016


Sir: Urinary neopterin:biopterin ratios are elevated in senile dementia of the Alzheimer type (SDAT) compared with age matched controls, due to a reduced conversion of dihydroneopterin triphosphate to tetra-hydrobiopterin.[1, 2] There is a similar elevated neopterin:biopterin ratio in Down's syn-drome, a condition producing a similar dementia to SDAT.

Morning urines were collected into ascor-bic acid (2% final concentration) from a group of 53 Downs sufferers of mixed sex aged between 1 to 70 years without any other disease and, following storage at - 20░C, the neopterin and biopterin levels were determined by HPLC after acid iodine oxidation [3]. Compared with a group of 35 healthy con-trols of mixed sex and aged 23 to 93 years, the neopterin:biopterin ratio was significantly elevated 3.44, 1.73 vs 1.12, 0.55 (mean, SD) p < 0.2% (table). Against a creatinine baseline biopterin levels were unaffected but the urin-ary neopterin levels were significantly increased (Table). No age trend was observed suggesting that these metabolic effects precede dementia onset. The elevated neopterin:biopterin ratio could be due to a disease related immune response causing stimulation of neopterin biosynthesis,[4] alth-ough all disease states known to produce such were absent and the rise is less pronoun-ced that in such conditions. It is known that there are disturbances in the immune system of Down's patients, [5] and it could be sugges-ted that these disturbances are causing the rise in urinary neopterin in a similar manner to viral and malignant disorders. However, it has been found that interferon gamma (IFNg) production is lower in Down's patients than in normal patients with infec-tion.[6] It is IFNg which stimulates the macrophages to produce neopterin in infectious disorders,[7] so any decrease in IFNg levels should result in similar or reduced levels of urinary neopterin and not the increased levels observed. A second possibility is the presence of greater levels of guanosinc triphosphate in the purine pool from an increased biosynthesis of purines as a result of the extra chromosome 21, which has the locus for some of the enzymes for purine biosynthesis.

The levels of neopterin and biopterin are measured against a creatinine baseline. In the Downs subjects creatinine clearance is repor-tedly lower, reflecting a reduced glomerular nitration rate,[8] and this could be causing a distortion in the results. However, creatinine clearance has a positive linear correlation with both neopterin and biopterin[9] so any reduction in the baseline will be compensated for by reduced pterin excretion. This would also account for the elevated levels of biopterins in the plasma of such subjects.[10]

There is a greater incidence of Alzheimer type changes in Down's syndrome patients than in the normal population,[11] and Down's syndrome has been suggested as a model for accelerated ageing.[12) However, there is no correlation between age and urinary N/B ratio in Down's syndrome from birth and not one acquired with age.

Table Neopterin and biopterin levels in Down's subjects and healthy controls
NNeopterin/Creatinine (mean, SD)Biopterin/Creatinine (mean, SD)Creatinine (mmol/l) (mean, SD)N:B (mean, SD)
Downs syndrome530.47, 0.320.17, 0.148.22, 5.33.44, 1.7
Control320.14, 0.170.11, 0.112.3, 11.81.12; 0.55
P< 0.2 %NSNS< 0.2 %
Units Ámol pteridine /mmol crealinine.



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12 Walford R, Barnett E. Fahey J. Gatti R. Grossman H. Hibrawi H, Motola M. Immunological and Biochemical Studies of Down's Syndrome as a Model of Accelerated Aging. In: Segre D, Smith L. eds. Immunological Aspects of Aging. New York: Marcel Dekker, 1981:479-532.