Atypical Phenylketonuria With Borderline or Normal Intelligence

Abstract

In the past, it was believed that nearly all patients afflicted with this disorder were mentally retarded. In a survey covering all published cases, Jervis 1 found that only three out of 330 phenylketonuric children (0.9%) had an intelligence quotient above 70. In 1960, Knox2 reported that there were 20 known untreated patients with phenylketonuria having "high grade" intelligence. Of these, eight patients had IQs between 60 and 69; six patients had IQs between 70 and 79; three patients had IQs between 80 and 89; and three patients had IQs over 90. More recently, Knox3 has expressed the view that no single factor can account for the relatively mild intellectual defect in these "atypical" phenylketonuric children. He believes that some of these have a biochemical defect which is often as severe as in the usual patient with phenylketonuria. But there appears to be a second group of patients with lower plasma phenylalanine levels; a few also have mildly affected relatives.The widespread screening for phenyl¬ ketonuria among newborn infants has led to the recognition that not all instances of hyperphenylalanemia are caused by

Phenylketonuria: a review

“…These infants have elevated serum phenylalanine levels of 4-20 mg per 100 ml, but the levels are not as high as those reached in classical phenylketonuria (Hsia, O'Flynn & Berman, 1968). On a normal diet, phenylpyruvic acid and orthohydroxyphenylacetic acid appear intermittently in the urine, but they nearly always appear with phenylalanine loading.…”

Can untreated PKU patients escape from intellectual disability? A systematic review

“…Classical symptomatology of untreated or late-treated classical PKU consists of severe to global developmental delay, seizures, psychiatric disorders, and profound ID, with IQ declining to 40 or lower at one year of age [ 24 ]. Early natural history and cohort studies, however, also showed that this severe clinical picture does not apply to all PKU patients, postulating that approximately 1–2% of the total PKU population would somehow have escaped from ID [ 10 , 25 ]. However, based on the number of identified PKU patients born before the introduction of neonatal screening with severe ID that seems to be far less than would be expected from the current prevalence of classical PKU patients found at neonatal screening [ 26 ], the incidence of such “unusual” PKU may be higher than previously thought and many “unusual” PKU patients seem to have remained unidentified.…”

Heterogeneity of phenylketonuria at the clinical, protein and DNA levels

“…The phenotype of phenylalanine hydroxylase (PAH, EC 1.4.16.i) deficiency has been known to be variable since the advent of the Guthrie and other tests allowed the study of large numbers of individuals with elevated serum and urinary phenylalanine and metabolites (McKusick 26160). This heterogeneity was detected first at the clinical level where some patients developed normally despite serum phenylalanine levels of greater than 20 #g//d (Hsia et al, 1968) and some individuals had intermediate phenylalanine levels (O'Flynn et al, 1967) now referred to as hyperphenylalaninaemia (HPA).…”