Functional vitamin B12 deficiency in phenylketonuria patients and healthy controls: An evaluation with combined indicator of vitamin B12 status as a biochemical index

Abstract

Background Vitamin B12 deficiency frequently appears in phenylketonuria patients having a diet poor in natural protein. The aims of this study were to evaluate vitamin B12 status in phenylketonuria patients by using combined indicator of vitamin B12 status (cB12) as well as methylmalonic acid and homocysteine, more specific and sensitive markers, in comparison with healthy controls. Methods Fifty-three children and adolescents with phenylketonuria under dietary treatment and 30 healthy controls were assessed cross-sectionally. Serum vitamin B12 and folate concentrations were analysed by chemiluminescence immunoassay. Plasma methylmalonic acid and total homocysteine concentrations were measured by liquid chromatography-tandem mass spectrometry and liquid chromatography, respectively. cB12 was calculated by using a formula involving blood parameters. Results Methylmalonic acid and folate concentrations in phenylketonuria group were higher compared with controls. Methylmalonic acid concentrations were high in 56.5% of the patients and 26.7% of the controls with normal vitamin B12 concentrations. Based on cB12, a significant difference within the normal values was detected between the groups. However, although 24.5% of phenylketonuria patients and 13.3% of controls had decreased vitamin B12 status according to cB12, there was no significant difference. Conclusion Children and adolescents with phenylketonuria having a strict diet can be at risk of functional vitamin B12 deficiency. This deficiency can be accurately determined by measuring methylmalonic acid concentrations. Calculation of cB12 as a biochemical index did not provide additional information compared with the measurement of methylmalonic acid alone, but may be helpful for classification of some patients with increased methylmalonic acid as having adequate vitamin B12 status.

Homocysteine and methylmalonic acid in Phenylketonuria patients

“…There was no consistent relationship between metabolic control and MMA and Hcy levels, although there were significant correlations between serum vitamin B12 and Hcy, MMA, and metabolic control. Using a combined calculation of vitamin B12, Akış et al (2020 ) found lower vitamin B12 in 24.5% of PKU patients and 13.3% of controls, but this difference was not significant.…”

“…MMA levels did not differ significantly, with values within the normal range. Akış et al (2020 ) found higher MMA concentrations in a PKU group than controls. MMA concentrations were high in 56.5% of the patients and 26.7% of the controls with normal vitamin B12 levels.…”

Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis

“…The included studies were published from 1994 [38] to 2023 [39], and their characteristics are detailed in Table 1. Four studies were conducted in Greece [25,27,40,41], three in Turkey [31,42,43], three in Spain [32,44,45], two in Austria [26,46], two in Chile [39,47], two in Japan [29,30], two in the United Kingdom [48,49], two in the USA [38,50], and one each in Germany [51], France [52], Poland [28], and Switzerland [53]. All studies, except for one case-control study [26], were cross-sectional and compared individuals with PKU to healthy controls.…”

“…Five studies assessed children [25,27,28,31,40], one studied adolescents [43], children and adolescents were included in nine studies [26,32,38,41,42,45,46,50,51,53], six studies examined adults [29,30,39,48,49,52], and the remaining two studies had a mixed population [44,47]. Most studies included males and females [24,[26][27][28][29][30]37,38,[40][41][42]45,46,[49][50][51][52], and while it was not explicitly stated in other studies [25,27,40,44,45,48,49], they likely involved both male and female participants. Table 2<...…”

Is the clinical course of non-arteritic ischemic optic neuropathy associated with oxidative damage and the dynamics of the antioxidant response?

“…Plasma MMA analysis: Plasma samples were collected in tubes containing EDTA anticoagulant and were centrifuged immediately at 4°C and 2000xg for ten minutes. The concentration of MMA was measured by LC-MS/MS (Shimadzu Prominence UFLC, Japan and 4000 QTRAP, Applied Biosystems, Germany, respectively), as described previously [11]. Intra-and inter-day MMA precisions were <3.8% and <5.7%, respectively.…”