Functional Biomarkers of Vitamin B12 Status, Diet, and Metabolic Control in Women with Phenylketonuria (P24-005-19)

Abstract

ObjectivesMetabolic control in Phenylketonuria (PKU) requires a protein-restricted diet, which elevates the risk of vitamin B12 deficiency. Neurological sequelae driven by suboptimal B12 status in PKU may be overlooked due to concomitant elevations in phenylalanine and B12 monitoring techniques that lack sensitivity. The aim of this analysis was to assess the effectiveness of functional biomarkers of B12 status, methylmalonic acid (MMA) and total homocysteine (tHcy), in the early identification of B12 deficiency in PKU. MethodsDiet and blood measures (plasma amino acids, B6; serum B12, folate, MMA, tHcy) were assessed in 31 females with PKU who attended the Emory Metabolic Camp in 2012 (N = 14) or 2018 (N = 17). The prevalence of functional B12 deficiency (MMA > 378 nmol/L and B12 < 914 pg/mL) was determined, and Spearman rank correlations between dietary intake, metabolic control, and biochemical indicators of B12 status were assessed (SAS 9.4, α = 0.05). ResultsAll characteristics were similar for 2012 and 2018 participants except tHcy, which was higher among females in 2012 (P = 0.01). Median age was 20 years (IQR: 16–24) and mean BMI was 29.6 ± 8.3 kg/m2. Of the 31 participants, 13 (41.9%) were on a phenylalanine-lowering medication (Kuvan). Five females (16%) had low B12 concentrations (<230 pg/mL), and one of these five had elevated MMA. Dietary consumption of B12 was below the RDA in seven females (22.6%), five of which also had suboptimal consumption of B6 and folate. Low B12 was associated with increased MMA (r = −0.49, P = 0.01) and tHcy (r = −0.42, P = 0.02) levels. Whereas, higher serum B12 was associated with elevated plasma B6 (r = 0.86, P < 0.01), dietary compliance (r = 0.41, P = 0.03), and increased intake of B12 (r = 0.63, P < 0.01), B6 (r = 0.47, P = 0.01), folate (r = 0.46, P = 0.01), and total protein (r = 0.43, P = 0.02). ConclusionsVitamin B12 has a moderate correlation with MMA and tHcy in females with PKU. Functional B12 deficiency, however, is not prevalent in this sample. This may reflect the regular consumption of fortified medical food among the females in this sample. Monitoring MMA and tHcy, regardless of B12 levels, may still have utility in this population for the detection of early deficiency. Funding SourcesNational Center for Advancing Translational Sciences of the NIH, private donations.