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Cognitive function in untreated subjects with mild hyperphenylalaninemia: a systematic review
Noushin Rostampour1,2, Rojin Chegini3, Silva Hovsepian4,5
1Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. rostampour_n@yahoo.com.
Background:
This systematic review study aims to evaluate the cognitive function of patients with mild hyperphenylalaninemia (mHPA) without treatment.
Methods:
A systematic literature search was done from the 1st of May to the 30th of July in 2021 on published studies. The search strategy was ((hyperphenylalaninemia) OR (phenylketonuria) AND (cognition)). We use PubMed, Scopus, and the Web of Science databases. Studies which reported their findings regarding the cognitive function of patients with mHPA (screening serum phenylalanine > 120 and < 600 μmol/L) were included and reviewed.
Results:
From initially retrieved 2805 studies, finally, 15 studies (10 on untreated patients with Phe levels below 360 μmol/L, 7 on untreated patients with Phe levels between 360 and 600 μmol/L, four 120-600 μmol/L) were selected. Most of the studies used the Wechsler Intelligence Scale for IQ evaluation, two (2/15) of them used the Stanford-Binet test and two used both tests. Four studies have reported a worse cognitive outcome compared to the control group, and in one study, relative defects in attention and working memory were reported. Other studies have reported normal IQ levels and no significant cognitive defects.
Conclusion:
It is suggested that Phe levels between 120 and 360 μmol/L are generally safe. Some studies showed that untreated patients with higher levels might show some degrees of cognitive impairment. In conclusion, current knowledge is insufficient to state that treatment is not required for HPA patients to preserve their cognitive status, especially in patients with Phe levels of 360-600 μmol/L. Further studies with a larger sample size and standardized cognitive function evaluation tools are needed.
Insights
Untreated mild hyperphenylalaninemia (mHPA) patients with phenylalanine levels between 120-360 μmol/L generally show safe cognitive function. However, higher levels (360-600 μmol/L) may indicate potential cognitive impairment, necessitating further research.
Area of Science:
- Biochemistry
- Neuroscience
- Genetics
Background:
- Mild hyperphenylalaninemia (mHPA) is a metabolic disorder characterized by elevated phenylalanine levels.
- Cognitive function in untreated mHPA patients requires further evaluation to determine safe phenylalanine thresholds.
Purpose of the Study:
- To systematically review and evaluate the cognitive function of patients with mild hyperphenylalaninemia (mHPA) who are not undergoing treatment.
- To assess the impact of different phenylalanine (Phe) levels on cognitive outcomes in untreated mHPA.
Main Methods:
- A systematic literature search was conducted across PubMed, Scopus, and Web of Science databases from May 1 to July 30, 2021.
- Included studies focused on patients with mHPA (serum phenylalanine 120–600 μmol/L) and reported cognitive function findings.
- The search strategy targeted studies combining "hyperphenylalaninemia" or "phenylketonuria" with "cognition".
Main Results:
- Fifteen studies were selected, analyzing cognitive function in untreated patients with phenylalanine levels ranging from 120 to 600 μmol/L.
- Four studies reported worse cognitive outcomes compared to controls, with one noting attention and working memory deficits.
- Most studies utilized the Wechsler Intelligence Scale for IQ assessment; others used the Stanford-Binet test or both.
Conclusions:
- Phenylalanine levels between 120–360 μmol/L appear generally safe for cognitive function in untreated mHPA.
- Higher phenylalanine levels (360–600 μmol/L) may be associated with cognitive impairment, suggesting treatment may be necessary.
- Current evidence is insufficient to conclude that treatment is unnecessary for all HPA patients; further large-scale studies with standardized tools are recommended.
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