The Impact of the First 2020 COVID-19 Lockdown on the Metabolic Control of Patients with Phenylketonuria

Abstract

The present study assessed patients’ metabolic control of phenylketonuria (PKU) during the first 2020 COVID-19 lockdown in Poland. Blood (phenylalanine) Phe results of the tests of 535 patients, performed in 2019 and in the first months of 2020, were analysed. The six-week lockdown period was compared to the preceding six-week period as well as to the two corresponding periods of 2019 (three non-lockdown periods). More patients failed to perform Phe tests in the lockdown period (32.7%) than in non-lockdown periods (15.6%, 15.1%, 17.2%; p < 0.001 for all). The median Phe levels for those patients who performed testing in all the four periods did not differ between periods. However, these patients tended to perform only one test during the lockdown (ORs: 1.43 to 1.60; 95% CI: from 1.01–2.04 to 1.11–2.30, p-value 0.02 to 0.005). Patients who did not take blood during the lockdown (46.7%) performed significantly fewer blood tests in the remaining periods (median <IQR>: 1 <0–1> vs. 2 <1–4>; p < 0.001). In conclusion, direct assessment of patients’ compliance based upon Phe levels during the pandemic lockdown was not possible. Pre-pandemic non-compliant patients frequently failed to perform the test during the lockdown, whereas the previously compliant ones were more likely to perform only one test. This strongly suggests that metabolic control might have worsened.

Phenylketonuria Patients’ and Their Caregivers’ Perception of the Pandemic Lockdown: The Results of a National Online Survey

“…These changes affected all the studied groups of patients. In a recent study [ 9 ], we documented decreased frequency of blood tests in paediatric PKU patients in the pandemic lockdown. Phe concentrations obtained by patients during the lockdown did not become higher; rather the subjects previously identified as non-compliant more often failed to do tests during the assessed period, while those subjects who earlier showed compliance more often performed one test only.…”

Protein substitutions as new-generation pharmanutrition approach to managing phenylketonuria

“…34) Evidence from both systematic reviews also shows that BH4 effectively reduces blood Phe concentrations, increases Phe tolerance among PKU patients responsive to sapropterin dihydrochloride, and appears to help improve the diet therapy of patients. 19,31) For example, the SPARK extension study found that, in children under 4 years of age, long-term sapropterin treatment alongside a Phe-restricted diet maintained a boosted dietary Phe tolerance that can last for more than 3.5 years. 43) A randomized-controlled (RCT) trial evaluating BH4 therapy reported that it did not appear to affect Phe variation in a small sample of BH4-responsive PKU patients.…”

“…47) Overall, it appears to be a moderately favorable shortterm effect of BH4 on decreasing Phe levels and enhancing metabolic control in various PKU groups; the possible long-term impacts of BH4 on cognition and/or quality of life remain unknown, and research continues. 31)…”

“…58) LNAA is considered a new protein substitute because the transport of Phe between the intestinal mucosa and BBB can reduce Phe concentrations through competitive inhibition by LNAA type 1, which has a high affinity for Phe expressed in the brain. 31,48) All LNAA carried by this transporter contain branched-chain amino acids (valine, leucine, and isoleucine), aromatic amino acids (Phe, Tyr, and Trp), and other amino acids, including histidine, threonine, and methionine, which are indispensable for protein synthesis in PKU. 31) There is limited evidence to confirm the ability of LNAA supplementation to reduce blood Phe levels and improve cognitive outcomes.…”

“…31,48) All LNAA carried by this transporter contain branched-chain amino acids (valine, leucine, and isoleucine), aromatic amino acids (Phe, Tyr, and Trp), and other amino acids, including histidine, threonine, and methionine, which are indispensable for protein synthesis in PKU. 31) There is limited evidence to confirm the ability of LNAA supplementation to reduce blood Phe levels and improve cognitive outcomes. 41) Owing to insufficient evidence regarding the long-term effects of LNAA therapy, it is now considered a short-term therapy option.…”