Effects of Diet and Behavior Therapy on Social and Motor Behavior of Retarded Phenylketonuric Adults: An Experimental Analysis

Abstract

Summarychanges in the central nervous system, when administered toThe effects of a low phenylalanine diet on six retarded phenylketonuric adults were assessed. An ABA individual-subject design was used in experiment I to assess the effects of a low phenylalanine diet on social and motor behavior. Following a baseline during which the subjects ingested a normal phenylalanine diet (phase A), a low phenylalanine diet (phase B) was administered in a double blind fashion. Finally, the baseline condition (phase A) was reinstated (normal diet). The low phenylalanine diet resulted in few significant behavioral changes for those subjects with which proper methodologic controls were employed. However, for two of six subjects motor behavior, including stereotypy and tremor, seem to have ameliorated. In experiment 11, applied behavior analysis techniques, including differential reinforcement of other behavior and time out, were combined to radically reduce the frequency of stereotypy and self-abuse exhibited by one of the six subjects of experiment I. SpeculationSingle-subject methodology borrowed from the experimental analy& of behavior revealed that a low phenylalanine diet was unsuccessful in producing significant desirable behavior changes in four adult retarded phenylketonuric subjects with ,proper experimental controls. ~o w e i e r , when behaiior therapy techniques were used with one of these same subjects, a rapid and dramatic reduction in stereotypy and self-abuse was observed.Classic phenylketonuria (PKU) is a recessively inherited disease which causes severe mental retardation in untreated patients. In Massachusetts, it occurs with an incidence of l in 15,000 births (30). The liver enzyme phenylalanine-hydroxylase which converts phenylalanine to tyrosine is absent in these individuals. Phenylalanine and related metabolites (e.g., phenylpyruvic acid, phenyllactic acid, and o-hydroxyphenylacetic acid) accumulate in the blood, spinal fluid, and urine of untreated patients (29). In these patients, structural changes occur in the central nervous system, particularly in myelination, severely affecting mental performance. IQ scores below 50 are common (38).PKU, when detected in infancy, is treated with a low phenylalanine diet with the amount of phenylalanine in the serum generally restricted to an amount below 10 mgldl (17). When initiated with children under 6 months of age, damage to the central nervous system may be totally prevented (8,18,26); even beginning a low phenylalanine diet as late as 2 years of age may be beneficial (12,15,33). However, when begun after 2 years of age, the low phenylalanine diet cannot prevent severe retardation (12, 50). Although diet treatment started after 2 years of age is ineffective in preventing or correcting structural older-PKU children and adults desirable changes in behavior have been reported (2,3,12,16,18,19,42,47).In perhaps the best controlled study, Frankenburg et al. (16) studied the social behaviors of 4-and 5-year-old PKU children not previously on any special diet. So...

Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria

“…Blood Phe concentrations changes were induced by introducing a Phe-restricted diet in untreated adults (M. C. Brown & Guest, 1999;Fitzgerald et al, 2000;Yannicelli & Ryan, 1995), by re-introducing a Phe-restricted diet in early-and late-treated adults who had discontinued diet (Bik-Multanowski et al, 2008;Finkelson, Bailey, & Waisbren, 2001;Gassió et al, 2003;Lee et al, 2009;Marholin et al, 1978;Schuett, Brown, & Michals, 1985), or by introducing a Phe load in early-treated adults (ten Hoedt et al, 2011). Effects on neuropsychiatric symptoms were generally based on clinical observations, not test scores.…”

“…Effects on neuropsychiatric symptoms were generally based on clinical observations, not test scores. Although most studies reported neuropsychiatric symptom improvement associated with better metabolic control, two blinded cross-over studies in late/untreated adults found little evidence of symptom reduction during low Phe periods (Lee et al, 2009;Marholin et al, 1978).…”

“…All seven single cohort intervention studies reported neuropsychiatric improvement upon introduction or resumption of a Phe-restricted diet. Of three blinded cross-over studies that assessed the effects of blood Phe, one study in early-treated PKU showed a significant worsening of mood state on Phe loading (ten Hoedt et al, 2011), while two studies in late/nevertreated adults found no significant change in the frequency of "challenging behaviors" upon resumption of a Phe-restricted diet (Lee et al, 2009;Marholin et al, 1978). The discrepancy between these results may reflect the Hawthorne effect that is the tendency of an individual to improve when followed through study participation.…”

Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997

“…In general, late treatment will have no eect on intellectual abilities, but in some cases neurological and behavioural symptoms can improve when Phe levels are brought below 600 lmol/L (10 mg/dL) for at least 3 months [23,24,27,40,74,90].…”

Psychopathology of patients treated early for phenylketonuria: results of the German collaborative study of phenylketonuria

“…It was demonstrated that even in untreated patients, introduction of a phenylalanine reduced diet alleviated behavioral problems, but there were also data showing that behavioral therapy might be more effective than a low phenylalanine diet in reducing behavioral disturbances (3). Second, studies in treated patients also reported introvert and extrovert symptoms as well as hyperactivity; apart from the biochemical explanations these articles also mentioned psychosocial factors and the special therapeutic situation as possible causes of the observed disturbances (4)(5)(6)(7).…”