Abstract
Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Although dietary and, in some cases, pharmacological treatment has been successful in preventing intellectual disability in PKU patients who are treated early, suboptimal outcomes have been reported, including bone mineral disease. In this systematic review, we summarize the available evidence on bone health in PKU patients, including data on bone mineral density (BMD) and bone turnover marker data. Data from cohort and cross-sectional studies of children and adults (up to 40 years of age) were obtained by searching the MEDLINE and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For each selected study, quality assessment was performed applying the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS I) tool. We found that mean BMD was lower in PKU patients than in reference groups, but was within the normal range in most patients when expressed as Z-score values. Furthermore, data revealed a trend towards an imbalance between bone formation and bone resorption, favoring bone removal. Data on serum levels of minerals and hormones involved in bone metabolism were very heterogeneous, and the analyses were inconclusive. Clinical trials that include the analysis of fracture rates, especially in older patients, are needed to gather more evidence on the clinical implications of lower BMD in PKU patients.
Highlights
Phenylketonuria (PKU, OMIM 261600) is an inborn error of phenylalanine (Phe) metabolism caused in most cases (98%) by an inherited deficiency in l-phenylalanine-4-hydroxylase (PAH; EC 1.14.16.1)activity, leading to elevated levels of Phe in body fluids [1]
We present a comprehensive overview of evidence from cohort and cross-sectional studies assessing bone status in PKU patients, including bone mineral density (BMD), bone turnover markers, and serum levels of minerals and hormones implicated in bone metabolism
We observed a trend towards an imbalance between bone formation and bone resorption, suggesting that bone turnover may be skewed in favor of bone removal
Summary
Phenylketonuria (PKU, OMIM 261600) is an inborn error of phenylalanine (Phe) metabolism caused in most cases (98%) by an inherited deficiency in l-phenylalanine-4-hydroxylase (PAH; EC 1.14.16.1)activity, leading to elevated levels of Phe in body fluids [1]. The success of treatment has, led to the discovery of secondary issues in the life-long outcome of PKU patients, including nutritional deficiencies in minerals, vitamins, and long chain polyunsaturated fatty acids [10,11,12,13], behavioral impairment [13,14], and mineral bone disease [15,16]. Such micronutrient nutritional deficiencies will be highly dependent on the compliance to the treatment
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