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Decreased bone mineralization in children with phenylketonuria under treatment
L Hillman1, C Schlotzhauer, D Lee
1Department of Child Health, Columbia, MO 65212, USA.
Insights
Children with phenylketonuria (PKU) experience reduced bone mineralization and lower bone formation markers, despite adequate protein intake. The exact cause, whether the disease or its treatment, remains unclear.
Area of Science:
- Biochemistry
- Pediatrics
- Metabolic Disorders
Background:
- Phenylketonuria (PKU) is a genetic disorder requiring a strict low-phenylalanine diet.
- Patients often rely on specialized elemental formulas for nutrition, impacting mineral intake.
- Bone health in children with PKU is a concern due to dietary modifications.
Purpose of the Study:
- To investigate the effects of PKU and its dietary management on bone mineralization in children.
- To compare bone mineral homeostasis and mineralization parameters between children with PKU and healthy controls.
Main Methods:
- Compared 11 children with PKU to a large group of normal children and an age/sex-matched subset.
- Assessed serum calcium, magnesium, phosphorus, zinc, copper, vitamin D metabolites, and parathyroid hormone.
- Measured bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA).
- Analyzed bone formation and resorption markers (e.g., bone alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase).
Main Results:
- Children with PKU had lower serum calcium and magnesium levels.
- Increased phosphorus tubular reabsorption suggested reduced intake or absorption.
- BMD was decreased in the lumbar spine and lower extremities in children with PKU.
- Markers of bone formation (bone alkaline phosphatase, osteocalcin, P1NP) were significantly lower.
- No differences were observed in bone resorption markers.
Conclusions:
- Children with PKU exhibit impaired bone mineralization and reduced bone formation.
- These deficits may be linked to the PKU disease process or its phenylalanine-restricted diet.
- Further research is needed to elucidate the specific etiology and guide interventions.
Abstract:
Children with phenylketonuria (PKU) obtain a great deal of their protein and mineral intakes from synthetic elemental formulae devoid of phenylalanine. To assess the effect of such diets and/or the disease on bone 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 compared 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 lower serum calcium (9.1 +/- 0.9 vs 10.4 +/- 1.9 mg/dl P < 0.01) amd magnesium (1.67 +/- 1.4 vs 2.07 +/- 0.16 mg/ dl, P < 0.001) but normal values for phosphorus, zinc, and copper. The percentage tubular reabsorption 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 protein intake was adequate. In the 11 pairs, a decreased bone mineral density 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 controls, decreases were seen in markers of bone formation; bone alkaline 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 carboxyterminal propeptide. No differences were seen in the bone resorption markers tartrate resistant acid phosphatase and urine Ca/Cr. The changes noted could not be related after age correction to serum phenylalanine levels, protein intake, or mineral intakes. It is unclear whether deficits in bone mineralization relate to the disease process itself or its treatment.