Summary
Phenylketonuria (PKU) is caused by an autosomal recessive deficiency of the enzyme phelnylalanine hydroxylase leading to a failure to convert phenylalanine to tyrosine. To avoid irreversible neurological damage because of increased phenylalanine, treatment is instituted rapidly after birth. We examined 31 adult PKU patients living on a less protein-restricted diet. Theoretically, these PKU patients had an increased risk of developing vitamin B12 and B6 deficiency because of a limited intake of animal products. Besides laboratory tests (n = 31) we obtained clinical information (n = 30) and detailed information on food consumption (n = 28). Three-quarters of the patients had early biochemical signs of vitamin B12 deficiency. In spite of a normal folate status, 9 (29%) had a plasma homocysteine above 12 μmol/L. In accord with these findings, the food questionnaires indicated that 11 (39%) patients received less than the recommended daily vitamin B12, and 20 (71%) received less vitamin B6 than recommended. A significant association was found between reduced vitamin B12 intake and both reduced serum cobalamins (p = 0.04) and reduced serum transcobalamin saturation (p = 0.03). Eleven patients took a vitamin pill daily, and these patients had a significantly lower plasma homocysteine compared to the rest. The present study suggests that adult PKU patients were at increased risk of developing vitamin B12 deficiency, and their intake of vitamin B6 was below the recommended daily intake. In conclusion PKU patients need continuing dietary guidance throughout adult life, and considering the risks, costs and potential benefits, daily vitamin supplementation seems justified in these patients.
Similar content being viewed by others
References
Aung TT, Klied A, McGinn J, McGinn T (1997) Vitamin B12 deficiency in an adult phenylketonuric patient. J Inherit Metab Dis 20: 603–604.
Becker W, Konde ÅB, Ohlander E-M, et al (2004) 4th Edition of the Nordic Nutrition Recommendations. Nordic Council of Ministers.
Bor MV, Refsum H, Bisp MR, et al (2003) Plasma vitamin B6 vitamers before and after oral vitamin B6 treatment: a randomized placebo-controlled study. Clin Chem 49: 155–161.
Carmel R (2001) Cobalamin deficiency. In: Carmel R, Jacobsen DW, eds. Homocysteine in Health and Disease. Cambridge University Press, 289–305.
Dyck PJ (1988) Detection, characterization, and staging of polyneuropathy: assessed in diabetics. Muscle Nerve 11: 21–32.
Guldberg P, Rey F, Zschocke J, et al (1998) A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype. Am J Hum Genet 63: 71–79. [Erratum: 63(4): 1252.
Hanley WB, Feigenbaum A, Clarke JT, Schoonheyt W, Austin V (1993) Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Lancet 342: 997.
Hanley WB, Feigenbaum AS, Clarke JT, Schoonheyt WE, Austin VJ (1996) Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Eur J Pediatr 155(Suppl 1): S145–S147.
Healton EB, Savage DG, Brust JC, Garrett TJ, Lindenbaum J (1991) Neurologic aspects of cobalamin deficiency. Medicine (Baltimore) 70: 229–245.
Leklem JE (1992) Vitamin B6. Reservoirs, receptors, and red-cell reactions. Ann N Y Acad Sci 669: 34–41.
Leklem JE (1996) Vitamin B6. In: Ziegler EE, Filer LJ, eds. Washington: ILSI Press, 174–183.
Moats RA, Moseley KD, Koch R, Nelson M Jr (2003) Brain phenylalanine concentrations in phenylketonuria: research and treatment of adults. Pediatrics 112: 1575–1579.
Nexo E, Christensen AL, Petersen TE, Fedosov SN (2000) Measurement of transcobalamin by ELISA. Clin Chem 46: 1643–1649.
Nexo E, Christensen AL, Hvas AM, Petersen TE, Fedosov SN (2002) Quantitation of holo-transcobalamin, a marker of vitamin B12 deficiency. Clin Chem 48: 561–562.
Rasmussen K (1989) Solid-phase sample extraction for rapid determination of methylmalonic acid in serum and urine by a stable-isotope-dilution method. Clin Chem 35: 260–264.
Refsum, H, Smith AD, Ueland PM, et al (2004) Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 50: 3–32.
Robinson M, et al (2000) Increased risk of vitamin B12 deficiency in patients with phenylketonuria on an unrestricted or relaxed diet. J Pediatr 136: 545–547.
Schulz B, Bremer HJ (1995) Nutrient intake and food comsumption of adolescents and young adults with phenylketonuria. Acta Paediatr 84: 743–748.
Ulleland M, Eilertsen I, Quadros EV, et al (2002) Direct assay for cobalamin bound to transcobalamin (holotranscobalamin) in serum. Clin Chem 48: 526–532.
Weiss N, Hilge R, Hoffmann U, et al (2004) Mild hyperhomocysteinemia: risk factor or just risk predictor for cardiovascular diseases? Vasa 33: 191–203.
Zschocke J (2003) Phenylketonuria mutations in Europe. Hum Mutat 21: 345–356.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hvas, A.M., Nexo, E. & Nielsen, J.B. Vitamin B12 and vitamin B6 supplementation is needed among adults with phenylketonuria (PKU). J Inherit Metab Dis 29, 47–53 (2006). https://doi.org/10.1007/s10545-006-0108-3
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10545-006-0108-3