Intelligence quotients and intelligence loss in patients with phenylketonuria and some variant states

Berman, Julian L.; Ford, Robin C.

doi:10.1016/s0022-3476(70)80233-5

Cited by 26 publications

(10 citation statements)

References 26 publications

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“…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).…”

Section: Speculationmentioning

confidence: 99%

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

et al. 1978

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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...

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Section: Speculationmentioning

confidence: 99%

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

et al. 1978

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“…However, abnormal amounts of aromatic acids can always be demonstrated after a phenylalanine load (1,17,24,28,30,35,36). Most patients, whether o n or off a diet, perform within the average range of intelligence (3).…”

Section: Speculationmentioning

confidence: 99%

Aromatic Acids in Urine of Healthy Infants, Persistent Hyperphenylalaninemia, and Phenylketonuria, before and after Phenylalanine Load

et al. 1974

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ExtractAromatic acids in urine were studied by gas chromatography and mass spectrometry in 3 premature and 7 full term healthy infants, in 2 patients with persistent hyperphenylalaninemia, and in 11 patients with phenylketonuria. Eleven aromatic acids were determined quantitatively.On a free diet, patients with phenylketonuria excreted large amounts of phenylacetic, mandelic, phenyllactic, o-OHphenylacetic, and phenylpyruvic acids ("phenylketonuria metabolites"), whereas the two patients with persistent hyperphenylalaninemia showed only a slightly abnormal excretion of these compounds. No or only very small amounts of phenylketonuria metabolites were found in healthy infants on normal diet, as well as in patients with persistent hyperphenylalaninemia or phenylketonuria on low phenylalanine diet.After an oral L-phenylalanine load (100 mg/kg) n o or only a slight increase of phenylketonuria metabolites was observed in the urine during the subsequent 24 h r in healthy infants o n normal diet, as well as in the two patients with persistent hyperphenylalaninemia o n low phenylalanine diet; in contrast, the concentration of these metabolites increased markedly in patients with phenylketonuria on low phenylalanine diet. This divergent response of the aromatic acids in urine to an oral phenylalanine load administered during a low phenylalanine diet probably represents a useful criterion for the differential diagnosis of these t w o conditions. SpeculationThe quantitative determination of the aromatic acids in urine before and after phenylalanine load can be considered as an indirect measurement of phenylalanine hydroxylase activity.after birth and remains subsequently mostly between 4 and 15 mg/100 ml. On a normal protein intake, it only rarely rises t o 20 or more mg/100 ml. The urine tests for aromatic acids (FeC13, DNPH, Phenistix) are usually negative and, with few exceptions (1,14,28,36), o-OH-phenylacetic acid as well as phenylpyruvic acid are not detectable by paper chromatography (12,17,29,30) or spectrophotometry (1). However, abnormal amounts of aromatic acids can always be demonstrated after a phenylalanine load (1,17,24,28,30,35,36). Most patients, whether o n or off a diet, perform within the average range of intelligence (3).Persistent hyperphenylalaninemia has t o be distinguished from other disorders of phenylalanine metabolism such as phenylalanine transaminase deficiency and transient hyperphenylalaninemia (see reviews in References 1 3 and 23). Patients with persistent hyperphenylalaninemia probably represent a biochemically and genetically heterogeneous group.In the present study, aromatic acids in urine were determined quantitatively by gas chromatography and identified by mass spectrometry. The investigation was performed in healthy infants, as well as in patients with persistent hyperphenylalaninemia and phenylketonuria, before and after a phenylalanine load. The patients were studied while on and off a low phenylalanine diet. SUBJECTS AND METHODSAromatic acid excretion in urine was studied in 3 h...

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“…1961, Bermanet af. 1966, Berman and Ford 1970, Hudson et af. 1970, Lonsdale and Foust 1970, Hanley et af.…”

Section: Introductionunclassified

Intellectual Development and Academic Achievement of Children Treated Early for Phenylketonuria

Berry¹,

O'Grady²,

Perlmutter³

et al. 1979

Develop Med Child Neuro

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SUMMARY Twenty early‐treated children with classical phenylketonuria (PKU), five early‐treated children with variant PKU and seven untreated children with hyperphenylalinemia were compared with non‐PKU family members in terms of intellectual development, and 14 school‐age PKU children were also compared for academic achievement. For the early‐treated children with classical PKU, mean IQ (98) was within the normal range, but nine of these 20 children had IQ scores more than ISD below those of family members. There was a significant negative correlation between phenylalanine concentrations at one to four years of age and later measured intelligence in these early‐treated children, but this was probably a consequence of poor dietary control in the early years. The early‐treated children with variant PKU and those with hyperphenylalaninemia had IQ scores consistent with those of unaffected family members, but untreated children with variant PKU had scores significantly lower than their own early‐treated siblings. Achievement scores of the early‐treated PKU children were consistent with their intellectual ability: they and their non‐PKU siblings had similar standard scores for reading and spelling, but arithmetic scores were significantly lower for the PKU children. Early‐treated children whose diet had been discontinued had achievement scores in all subjects below those predicted from their IQS. RÉSUMÉ Développement intellectuel et performances scolaires chez des enfants phénylcétonuriques précocement traités 20 enfants précocément traités avec phénylcétonurie classique (PCU), cinq enfants précocément traités avec PCU variante et sept enfants non traités avec hyper‐phénylalaninémie ont été compareés avec des membres de même famille non PCU en termes de développement intellectuel et 14 enfants PCU d' âge scolaire ont étéégalement compareés pour performances scolaires. Pour les enfants précocément traités avec PCU classique, le QI moyen (98) était dans les niveaux normaux, mais neuf de ces 20 enfants avaient un QI de plus de un écart‐type au‐dessous des membres de leur famille. Il y avait une corrélation négative significative entre les concentrations de phenylalanine de un à quatre ans et l' ‘intelligence appréciée ultérieurement chez ces enfants précocément traités, mais cela était probablement la conséquence d' un contrôle diététique médiocre dans les premiers âges. Les enfants précocément traités avec PCU variante et ceux avec hyperphénylalaninémie avaient des QI comparables à ceux des membres de leur famille indemnes mais les enfants non traités avec PCU variante présentaient des résultats significativement plus bas que ceux de leurs propres fréres ou soeurs traités précocément. Les performances scolaires des enfants PCU précocément traités correspondaient à leur capacityé intellectuelle = les scores standards pour la lecture et l'orthographe dtaient identiques à ceux des frères et soeurs non PCU mais les scores d' arithmétique étaient significativement plus bas pour les enfants PCU. Les enfants précocément traité...

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Intelligence quotients and intelligence loss in patients with phenylketonuria and some variant states

Cited by 26 publications

References 26 publications

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

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

Aromatic Acids in Urine of Healthy Infants, Persistent Hyperphenylalaninemia, and Phenylketonuria, before and after Phenylalanine Load

Intellectual Development and Academic Achievement of Children Treated Early for Phenylketonuria

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