Reduced macular thickness and macular vessel density in early-treated adult patients with PKU.

PURPOSE: Macular structure is poorly evaluated in early-treated phenylketonuria (ETPKU). To evaluate potential changes, we aimed to examine retinas of PKU patients using optical coherence tomography (OCT) with additional OCT angiography (OCTA) and compare the results to healthy controls. METHODS: A total of 100 adults were recruited in this monocentric, case-control study: 50 patients with ETPKU (mean age: 30.66 ± 8.00 years) and 50 healthy controls (mean age: 30.45 ± 7.18 years). Macular thickness, vessel density and flow area of the right eye was assessed with spectral domain OCT angiography SD-OCT(A). Macular microstructural data between the ETPKU and control group was compared. In the ETPKU group, the relationship between visual functional parameters (best corrected visual acuity [VA], spherical equivalent [SE], contrast sensitivity [CS] and near stereoacuity) and microstructural alterations was examined. The dependency of OCT(A) values on serum phenylalanine (Phe) level was analysed. RESULTS: There was significant average parafoveal and perifoveal total retinal layer thinning in ETPKU patients compared to healthy controls (p < 0.016 and p < 0.001, respectively), while the foveal region remained unchanged in the ETPKU group. Whole macular and parafoveal superficial capillary plexus density was significantly decreased in ETPKU compared to controls (p < 0.001). There were no significant differences in the foveal avascular zone, nonflow area, macular superficial and deep capillary plexus between the groups. The temporal parafoveal inner retinal layer thickness was found to negatively correlate with individual Phe levels (r = -0.35, p = 0.042). There was no difference in vascular density and retinal thickness in the subgroup analysis of patients with good therapy adherence compared to patients on a relaxed diet. CONCLUSIONS: Durable elevation in Phe levels are only partially associated with macular retinal structural changes. However, therapy adherence might not influence these ophthalmological complications.

Intra-familiar discordant PKU phenotype explained by mutation analysis in three pedigrees.

Classical phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are two phenotypes of phenylalanine hydroxylase (PAH) deficiency with different degrees of severity. We have analyzed three families in which classical PKU, MHP and a normal phenotype occurred within each family due to the different combinations of three mutations segregating within the family. Indeed, sequence PAH analysis revealed three different alleles segregating in each family. This report suggests that when discordant phenotypes occur in a family, complete analysis of the PAH gene may be performed in order to support the diagnosis and assist in accurate genetic counseling and patient management. We further support the marked heterogeneity of hyperphenylalaninemia primarily due to allelic heterogeneity at the PAH locus.