DECREASED BONE MINERALIZATION IN CHILDREN WITH PHENYLKETONURIA UNDER TREATMENT

Children with phenylketonuria (PKU) obtain a great deal of their prote in and mineral intakes from synthetic elemental formulae devoid of phe nylalanine. To assess the effect of such diets and/or the disease on b one mineralization, children with PKU were compared to normal children for many parameters of mineral homeostasis and bone mineralization. A total of 11 children with PKU of mean age 10.9 +/- 4.2 years were com pared to a large group of normal control children mean age 11.4 +/- 4. 2, and an age and sex matched subset (n = 11). Children with PKU had l ower serum calcium (9.1 +/- 0.9 vs 10.4 +/- 1.9 mg/dl P < 0.01) and ma gnesium (1.67 +/- 1.4 vs 2.07 +/- 0.16 mg/dl, P < 0.001) but normal va lues for phosphorus, zinc, and copper. The percentage tubular reabsorp tion of phosphorus was increased in PKU (93 +/- 3% vs 88 +/- 6%, P < 0 .05) suggesting a lower phosphorus intake and/or absorption. Serum 25- hydroxyvitamin D, parathyroid hormone and 1,25 dihydroxyvitamin D were similar in PKU and control children. Serum albumin and lean body mass by dual energy X-ray absorption were not different suggesting that pr otein intake was adequate. In the 11 pairs, a decreased bone mineral d ensity was seen for the lumbar spine (0.61 +/- 0.15 vs 0.72 +/- 0.24 P < 0.05), and lower extremities (1.56 +/- 0.30 vs 1.87 +/- 0.56 P < 0. 05) by paired t-test. Compared to the total controls and the paired co ntrols, decreases were seen in markers of bone formation; bone alkalin e phosphatase, (72 +/- 30 vs 126 +/- 43 P < 0.001), osteocalcin (10.7 +/- 3.4 vs 13.1 +/- 2.0 P < 0.05) and procollagen type I carboxytermin al propeptide. No differences were seen in the bone resorption markers tartrate resistant acid phosphatase and urine Ca/Cr. The changes note d could not be related after age correction to serum phenylalanine lev els, protein intake, or mineral intakes. It is unclear whether deficit s in bone mineralization relate to the disease process itself or its t reatment.