Vitamin/mineral and micronutrient status in patients with classical phenylketonuria

Strict low-phenylalanine diet is associated with an increased risk of developing micronutrient deficiencies in patients with phenylketonuria (PKU). The primary objective of this single-center, case-control study was to assess the nutritional parameters of patients with PKU on strict low-phenylalanine diet without vitamin and mineral supplementation compared to a healthy control group. Secondary objective was to identify the adequacy of vitamin/mineral supplementation in phenylalanine-free (Phe-free) amino acid formulas.

A total of 112 age- and sex-matched patients with PKU and 36 controls who did not take vitamin or mineral supplementation at least for the last 6 months were enrolled in the study. Biochemical and hematological markers including hemoglobin, serum vitamin B12, folic acid, iron, ferritin, transferrin saturation, copper, prealbumin, albumin, total protein, phosphorus, calcium, 25-hydroxy vitamin D, zinc, vitamin A and vitamin E levels were screened from fasting morning blood samples.

One hundred and twelve patients with classical PKU (53 females, 47.3%) and 36 healthy controls (18 females, 50.0%) were enrolled in the study. The mean age of patients with PKU was 136.8 ± 82.1 months (18-377). Median serum vitamin B12 level of patients with PKU was found to be higher than the control group (p = 0.002). Vitamin B12 deficiency was 15.2% and 30.6% in patients with PKU and healthy controls, respectively (p = 0.040). Mean serum folic acid level was higher in patients with PKU than the control group (p < 0.0001). In 55.4% of patients with PKU, and 2.8% of the control group, serum folic acid level was above the reference range (p < 0.0001). The frequency of ferritin and prealbumin values above the reference range was found to be higher in patients with PKU compared to the control group (44.4% vs 16.9%, p = 0.001; 38.8% vs 22.1%, p = 0.020, respectively). 25-Hydroxy vitamin D deficiency was detected in 53.6% and 47.2% of patients with PKU and the control group, respectively. Mean serum copper level was higher in the well-controlled (114.3 ± 26.7 μg/dL) group than the poorly controlled group (101.0 ± 29.1 μg/dL) (p = 0.022).

Phe-free amino acid formulas provide adequate vitamin A and zinc levels in patients with PKU, and result in excess folic acid, vitamin B12, copper and vitamin E values that are higher than required levels. Our results demonstrate a high percentage of vitamin D deficiency in patients with classical PKU and also in healthy controls in Turkey.