Evaluation of Treatment Begun in First Three Months of Life in 184 Cases of Phenylketonuria

Hudson, F. P.; Mordaunt, V.; Leahy, I.

doi:10.1136/adc.45.239.5

Cited by 60 publications

(17 citation statements)

References 9 publications

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“…1967;F uller and Shuman, 1969;H udson et al, 1970]. These early treated patients are generally of slightly lower intelligence than the normal population, but they are educated at normal schools and differ strikingly from most untreated or late treated PKU children [Aminogran booklet, 1971], The successful management of a PKU child depends on early di agnosis, monitoring of phenylalanine serum levels, skilled medical and dietetic advice and a high degree of cooperation and motivation on the part of the parent.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Dental Caries in Phenylketonuric Children

Winter¹,

Murray²,

Goose³

1974

Caries Res

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Phenylketonuria is a rare inherited metabolic defect in which there is a deficiency of the liver enzyme phenylalanine hydroxylase. Unless this condition is diagnosed within the first few weeks of life, and treated with special diets which have a high carbohydrate content, but which are very low in phenylalanine, severe mental deficiency can result. 105 phenylketonuric (PKU) children, aged 10 months to 16 years, were examined to determine whether this special diet had any effect on the prevalence of caries in PKU children. It was concluded that caries experience in the PKU children examined was of the same order as that reported in normal children of comparable age.

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Section: Discussionmentioning

confidence: 99%

Prevalence of Dental Caries in Phenylketonuric Children

Winter¹,

Murray²,

Goose³

1974

Caries Res

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“…When begun early and consistently maintained, this diet averts the most severe consequences of PKU. Neither gross structural brain damage nor global cognitive impairments are found (e.g., Bickel et al, 1954;Hudson et al, 1970;Williamson et al, 1981). Unfortunately, recent data indicate that there are deficits in the cognitive abilities dependent on frontal cortex even in children who have been on a restricted diet since birth, if those children have three-to fivefold elevations in plasma Phe (e.g., Welsh et al, 1990;A.…”

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confidence: 99%

An animal model of early-treated PKU

et al. 1994

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Phenylketonuria (PKU) is a genetic disorder in which the hydroxylation of phenylalanine (Phe) to tyrosine is severely disrupted. If PKU is left untreated, severe mental retardation results. The accepted treatment is to restrict dietary intake of Phe. It has generally been thought that cognitive impairments are prevented if levels of Phe in plasma are maintained at or below five times the normal level. However, we recently documented that children treated early and continuously for PKU or children mildly hyperphenylalaninemic, who have levels of Phe in plasma approximately three to five times normal, still have cognitive impairments. These impairments are specific to the functions of frontal cortex (A. Diamond, W. Hurwitz, E. Lee, W. Grover, and C. Minarcik, unpublished observations). To investigate the mechanism underlying these cognitive deficits, an animal model of this condition was developed and characterized. Thirty-six rat pups were divided into three groups. The first group was treated pre- and postnatally with Phe and alpha-methylphenylalanine (a phenylalanine hydroxylase inhibitor). The second group was injected postnatally with Phe and alpha- methylphenylalanine. The third group received postnatal control injections. The mild plasma Phe elevations in the two experimental groups produced significant behavioral and neurochemical effects. Both experimental groups were impaired on a task dependent on frontal cortex, delayed alternation. Levels of dopamine, homovanillic acid (HVA), norepinephrine, and 5-hydroxyindole acetic acid (5-HIAA) were measured in medial prefrontal cortex, anterior cingulate cortex, striatum, and nucleus accumbens. The largest neurochemical reductions observed were in HVA and were in the two frontal cortical areas (medial prefrontal cortex and anterior cingulate cortex). There were modest reductions in HVA in the nucleus accumbens but no significant changes in HVA, or in any other metabolite or neurotransmitter, in the striatum. The levels of 5-HIAA were also reduced in all brain regions examined. There was no effect on norepinephrine in any of the four regions examined. Reduced levels of HVA in medial prefrontal cortex were the only neurochemical effect that significantly correlated with every measure of performance on the delayed alternation task. This study provides evidence of deleterious effects from mild elevations in the levels of Phe in plasma previously considered small enough to be safe. These effects include impaired performance on a cognitive task dependent on frontal cortex and reduced HVA levels in frontal cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…There is widespread agreement that normal intellectual development can only be achieved when therapy begins very early and is strictly maintained during childhood [7,8,21,27,30,34], although normalization of serotonin levels can be achieved by the initiation of treatment at any age. However, certain therapeutic improvements of motor behavior have been reported, even when therapy was started late in infancy or during childhood, e.g., increased ability of locomotion, decrease of muscle tone and excitability, increased awareness of the surroundings, disappearance of seizure activity both clinically and in the EEG [4,9,12,26,43,44,67].…”

Section: Sleep Spindles Brain Development and Effect Of Dietary Trementioning

confidence: 99%

Sleep Patterns in Hyperphenylalaninemia: A Lesson on Serotonin to be Learned from Phenylketonuria

et al. 1973

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ExtractSleep behavior and bioelectric brain development have been studied by means of polygraphic recordings (respiration, eye movements, muscle activity, and electroencephalogram (EEG)) in 22 infants and young children with phenylketonuria (PKU). The EEGs were analyzed by a special visual pattern recognition program as well as by means of computer spectral analysis. The distribution between rapid eye movement (REM) or active and non-REM (NREM) or quiet sleep was not found to be different from control infants of the same age. Quite contrary to current theories on the biochemical regulation of sleep as derived from acute animal experiments, our results indicate that, under chronic conditions, a normal sequence of quiet and active sleep can be maintained despite a severe lack of blood and cerebrospinal fluid serotonin as it occurs in hyperphenylalaninemia. In the EEG of subjects with PKU the development of a rhythm or sleep spindle (12-16 cps) activity was enhanced and already abnormal as early as 5 weeks after term birth. The frequency of a waves as well as of hypnagogic, monomorphic, 6 activity was shifted toward higher values. Dietary treatment of 4-6 weeks duration and normalization of blood phenylalanine levels did not significantly change the abnormal bioelectric phenomena. SpeculationThe increase in high frequency regular rhythmic activity in the sleep EEG of subjects with PKU can be explained by decreased concentrations of inhibitory synaptic transmitters such as serotonin and 7-aminobutyric acid. The developmental course in the expressivity of sleep spindles during the 1 st year of life, together with reliable methods of quantified EEG analysis, seems to be a rather sensitive indicator of normal or abnormal brain maturation. Introductionshould be, in theory, alterations of sleep behavior be-

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Evaluation of Treatment Begun in First Three Months of Life in 184 Cases of Phenylketonuria

Cited by 60 publications

References 9 publications

Prevalence of Dental Caries in Phenylketonuric Children

Prevalence of Dental Caries in Phenylketonuric Children

An animal model of early-treated PKU

Sleep Patterns in Hyperphenylalaninemia: A Lesson on Serotonin to be Learned from Phenylketonuria

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