OBJECTIVES@#To retrospectively analyze the variation and characteristics of
phenylalanine hydroxylase (PAH)
gene, and to observe the long-term
treatment effect and follow-up of
newborns with
PAH deficiency.@*
METHODS@#Clinical data,
treatment and follow-up results of 198
patients with
PAH deficiency diagnosed by
newborn screening in Jinan from 1996 to 2021 were collected. The genetic
analysis of 55
patients with
PAH deficiency diagnosed by
newborn screening in Jinan and 213
patients referred from the surrounding areas of Jinan were summarized.
Gene variations were checked by a customized Panel
gene detection method.
Blood phenylalanine-concentration and physical
development indicators including height and weight were regularly monitored. Intellectual development was assessed using a neuropsychological development scale for
patients aged 0-6 years and
academic performance, and
brain injury in
patients was assessed using
brain magnetic resonance imaging.@*RESULTS@#c.728G>A, c.158G>A, c.721C>T, c.1068C>A, c.611A>G variations were common in PAH
gene. The
genotype of c.158G>A variation is compound heterozygous variation, with mainly a mild hyperpheny-lalaninemia. 168
patients with
PAH deficiency who were followed-up regularly had normal physical development without
dwarfism or
malnutrition. Among the 33 preschool
patients who underwent mental development assessment, 2 were
mentally retarded and the initial
treatment age was older than 6 months. Nine
patients with an average age of (17.13±2.42) years completed
brain magnetic resonance imaging, one case was normal, and 8 cases were abnormal. There were patchy or patchy hyperintense foci near the bilateral
lateral ventricles on T2WI, and the intellectual development was normal. Compared with the other eight
patients, the
blood phenylalanine concentration of the normal
child was better and stably controlled within the ideal range.@*CONCLUSIONS@#c.728G>A, c.158G>A, c.721C>T, c.1068C>A, c.611A>G variations were common in PAH
gene. After standardized
treatment, most
patients with
PAH deficiency diagnosed by
screening can obtain normal
growth and intellectual development in
adolescence, but there are different degrees of organic lesions in the cerebral
white matter.