Neurological improvement following reinstitution of a low phenylalanine diet after 20 years in established pnenylketonuria

Abstract

SUMMARYA 41-year-old woman had meaningful functional improvement following reinstitution of a low phenylalanine diet. She was diagnosed at birth with phenylketonuria and followed strict dietary adherence till the age of 16. Thereafter the diet was discontinued. She subsequently presented with subacute profound visual loss, cognitive dysfunction and paraparesis such that she was bed bound requiring full nursing care. Following dietary intervention there was meaningful improvement such that she was no longer demented and while her vision remains poor she is now independent for activities of daily living. This case report suggests that consideration of reimplementation of dietary intervention is warranted even after a prolonged period of time. BACKGROUND

Saccadic reaction time and ocular findings in phenylketonuria

“…On the other hand, there was a third study participant with missed newborn screening, who presented normal eye findings. Our results are in line with the few case reports on eye findings in patients with phenylketonuria during the twentieth century [4][5][6], in which cataract development was not directly related to PKU, but rather due to blunt trauma (often selfinduced, and unilaterally), or due to high dosages of thioridazine (bilateral cataract) [4,18]. Before the era of the newborn screening however, deficient pigmentation leading to blond hair and pale blue irides was common, with photophobia as a frequent result.…”

“…Ocular findings in patients with phenylketonuria comprise a broad range of findings such as photophobia, ocular hypopigmentation, cataract, corneal clouding [4], subluxation of the lens [5], pallor of the optic disc and eventually even bilateral vision loss [6]. All of them occurred in rare cases.…”

The outcome of white matter abnormalities in early treated phenylketonuric patients: A retrospective longitudinal long-term study

“…Thereafter similar alterations were detected in untreated, late-treated and also in early and continuously treated PKU patients that did not show any neurological symptom [1,6,7]. Curiously, after the few initial cases, no further PKU patients experiencing neurological deterioration have been reported in the literature so far apart from three subjects suffering a progressive visual loss that was reversed by diet restoration (see Rubin et al 2013 [8], Anwar et 2013 [9] and Leuzzi unpublished case). This is a puzzling aspect considering that the discovery of MRI white matter alterations in PKU patients played a role in favor of the option of diet for life at the end of the '80ies.…”

Neuropsychological outcomes in phenylketonuria.

“…In our own review of within-participant studies, all studies but one showed results in this direction. Following diet initiation, late-treated CwPKU demonstrated improved compliance and increased interest in their surroundings (e.g., Schuett et al, 1985) as well as reduced levels of self-injury, irritability, and aggression (e.g., Dion et al, 2001;Fitzgerald et al, 2000); early-treated CwPKU showed improved mood and behavior (Douglas et al, 2013); and early-treated AwPKU showed decreased levels of fatigue, depression, and distress (Anwar et al, 2013;Bik-Multanowski et al, 2008;ten Hoedt et al, 2011). It should be pointed out, however, that effects on well-being have been measured with questionnaires (N = 4), observations (N = 9), and caregivers' reports (N = 4), which are more susceptible to placebo bias than direct performance measures.…”