First results of the newborn screening for phenylketonuria as a part of an expanded neonatal screening in the Krasnodar region

Introduction. Since 01/01/2023, expanded neonatal screening (ENS) has been carried out in the Russian Federation, where blood is collected from newborns in the first 24-48 hours of life; to diagnose phenylketonuria, instead of the previously used fluorimetric method, the tandem mass spectrometry (TMS) method has been used.

Purpose. To evaluate the results of screening newborns for PKU in relation to earlier blood sampling and a different method of determining blood phenylalanine (Phe).

Methods. An analysis of the results of examinations for PKU of children born in the Krasnodar region from 1 January 2023 to 31 July 2024 was carried out. Capillary blood sampling was carried out in the first 24-48 hours of life in full-term newborns and on the 7th day in premature infants. The concentration of Phe, tyrosine (Tyr) in the blood and the Phe/Tyr ratio were determined by TMS on a QSight 225MD Screening System (Finland) using NeoBase 2 kits.

Results. During this period, 81,383 children were born in the region, 81,193 (99.8%) were examined within the framework of the ENS. 32 children with hyperphenylalaninemia (HPA) and 3 heterozygous carriers of pathogenic variants in the PAH gene were identified, the frequency of the disease was 1:2537, which is 2.9 times higher than the frequency of PKU previously determined according to neonatal screening (NS). The threshold level of Phe was determined to be 20-97 μM/l, the Phe/Tyr ratio was 0-2.2. Of the 32 children with hyperphenylalaninemia (HPA), 13 were diagnosed with classic PKU, and 19 were diagnosed with mild HPA. During examination in maternity hospitals, the blood Phe level in identified patients ranged from 96 to 602 μM/l, the Phe/Tyr ratio – from 0.9 to 14.0. According to the results of the molecular genetic study, 2 children (6.3%) were identified with 2 mild mutations in the PAH gene, 16 (50%) with 1 mild and 1 severe mutation, 7 (21.9%) with two severe mutations, 7 (21.9%) – with 1 or 2 mutations of uncertain severity.

Conclusions. Examination of newborns for PKU as part of the ENS allows for the timely identification of children not only with classic PKU, but also with mild forms of HPA. Changing the timing of newborn screening during ENS requires careful consideration of threshold  levels of Phe and the Phe/Tyr ratio to prevent missing children with HPA.

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