Saccadic reaction time and ocular findings in phenylketonuria

Susanne Hopf,Caroline Nowak,Irene Schmidtmann,Julia B Hennermann,Susanne Pitz,Norbert Pfeiffer

doi:10.1186/s13023-020-01407-7

Abstract

BackgroundPhenylketonuria (PKU) is an inherited metabolic disorder characterized by reduced activity of phenylalanine hydroxylase resulting in elevated blood phenylalanine (Phe) concentration. Despite some obvious ocular changes, the disorder has been poorly recognized by ophthalmologists. Neurophysiologic tests imply prolonged reaction time correlating with increased phenylalanine blood concentrations. We aimed to test saccadic reaction time in PKU patients in dependency of blood phenylalanine concentrations.MethodsNineteen biochemically diagnosed PKU patients and 100 controls completed comprehensive ophthalmologic and orthoptic examinations including saccadometry by infrared based video-oculography. Peak velocity, gain, and particularly latency of reflexive saccades were compared to controls, and regression analysis was performed.ResultsLatency of reflexive saccades was not associated with the current phenylalanine concentration. Although in 10 out of 19 patients phenylalanine concentrations were outside the age-related therapeutic range, latency differed little between PKU patients and the controls, as well as peak velocity and gain. Ocular findings occurred as partial hypopigmentation of the iris in one late diagnosed patient aged 36 years, and as bilateral cataracts (possibly due to steroid intake) with refractive amblyopia, strabismus, high myopia, and glaucoma in another late diagnosed patient aged 46 years. Visual acuity was reduced in eight PKU patients.ConclusionsSaccadometry, particularly saccadic reaction time, is not useful in the monitoring of phenylketonuria. Ophthalmic examination is recommended in PKU patients, as the occurrence of ocular pathologies was relatively high.

Highlights

Phenylketonuria (PKU) is an inherited metabolic disorder characterized by reduced activity of phenylalanine hydroxylase resulting in elevated blood phenylalanine (Phe) concentration
On the basis of reflexive saccades, we aimed to evaluate if saccadic latency could be a simple, non-invasive follow-up surrogate to the conventional phenylalanine blood test
A detailed clinical table of each patient including ophthalmic laboratory data is given in the additional file 2

Summary

Introduction

Phenylketonuria (PKU) is an inherited metabolic disorder characterized by reduced activity of phenylalanine hydroxylase resulting in elevated blood phenylalanine (Phe) concentration. We aimed to test saccadic reaction time in PKU patients in dependency of blood phenylalanine concentrations. Context and summary of the literature Phenylketonuria (PKU) is an inherited disease of amino acid metabolism, with a prevalence of 1:5,352 in Germany (148 new cases in 2016) [1]. We tested saccades as a potentially new parameter for therapy control, as saccades are under dopaminergic control, too [10, 11] This would be in line with the ocular motor findings in other metabolic diseases than PKU such as Morbus Gaucher type 3 and Niemann Pick Type C, which show disturbances in horizontal and vertical saccadic eye movements, respectively [12, 13]

Objectives

Methods

Results

Conclusion