Neuropsychologic Functions of Early Treated Patients with Phenylketonuria, on and off Diet: Results of a Cross-National and Cross-Sectional Study

Abstract

Twenty-two French patients with early treated phenylketonuria (PKU) off diet (no reduced phenylalanine, Phe) since their 5th birthday, 23 German patients on diet (reduced Phe), and 21 healthy control subjects from childhood to adulthood matched for age, sex, and IQ were investigated for visuomotor reaction time, sustained attention, and visual stimulus scanning. Determinations were made whether 1) the three groups showed different developmental trends in their reaction times, 2) the threshold of a Phe blood level of 360 mumol/L formulated in recent recommendations can be regarded as safe, 3) test performances are related to the quality of dietary control in the same way for all age groups, and 4) long-term elevated Phe levels result in aggravating effects of increasing differences between patients on and off diet and healthy controls. Results revealed that developmental trends were similar in all treatment groups. Only children with a mean Phe level below 360 mumol/L performed as well as control subjects. Differences between treatment groups decreased in adulthood, and no aggravating effect could be observed. Mean performance of patients with mild PKU off diet was in the same range as performance of patients with classical or mild PKU on diet, calling into question the benefit of treating these patients. It is concluded that it is preferably safer to maintain Phe blood levels below 360 mumol/L at least during the first 10 y of life.

Motor function under lower and higher controlled processing demands in early and continuously treated phenylketonuria.

“…However, myelin deficiencies may explain reduced processing speed as well (Bick et al, 1991;Cleary et al, 1994;Koester, 1991;Rowland, 1991). Reduced vigilance and sustained attention, which have consistently been reported for PKU patients (Burgard et al, 1997;, may also result in slower (mean) processing speed. Reduced levels of noradrenaline (metabolites), which is associated with vigilance and sustained attention (Posner, 1993;Robbins & Everitt, 1994), have been found in the cerebrospinal fluid and autopsied brains of PKU patients (Krause et al, 1985;Lou, Lykkelund, Gerdes, Udesen, & Bruhn, 1987;McKean, 1972).…”

“…Burgard et al, 1997). Impaired performance by PKU patients compared with control participants in the tracking and pursuit tasks showed deficiencies in motor control capacity.…”

Management of Phenylketonuria for Optimal Outcome: A Review of Guidelines for Phenylketonuria Management and a Report of Surveys of Parents, Patients, and Clinic Directors

“…Many reports have shown that optimum outcome occurs when dietary therapy is started early and continued indefinitely. 22,[25][26][27][28][29][30][31][32][33][34][35][36] As with other chronic illnesses, decreased compliance and poor dietary control increase with age, especially after 6 years of age. 17,25,37,38 Older individuals who have discontinued dietary therapy are at risk for developing loss of intelligence, magnetic resonance imaging findings consistent with white matter dysfunction, and occasionally acute demyelinating neuropathies.…”

Nutritional Changes and Micronutrient Supply in Patients with Phenylketonuria Under Therapy with Tetrahydrobiopterin (BH4)

“…Discontinuation of dietary treatment bears a high risk of nutrient deficiencies, cognitive and emotional dysfunction as well as behavioral problems. Therefore, lifelong diet is strongly recommended (Stemerdink et al 2000;Burgard et al 1997;Weglage et al 1992).…”