Objective: Hyperphenylalaninemia (HPA) is an inborn error of metabolism in which the hydroxylation of phenylalanine (Phe) to tyrosine is disturbed. Accumulation of Phe leads to severe mental and psychomotor retardation. (1)H magnetic resonance spectroscopy ((1)HMRS) is a novel non-invasive method to quantitate the brain metabolites besides Phe concentration in HPA patients. And it could be acquired conveniently on clinical MRI routine scanners. This study aimed to investigate the correlation between blood Phe ([Phe](blood)) and [Phe](brain), the characteristics of blood-brain Phe metabolism and its impacts on mental retardation.
Method: Totally 32 untreated patients diagnosed with HPA were studied, including 18 boys and 14 girls (age ranging from 33 days to 13 years). The patients were divided into two groups: elder than 4 months old (n = 22) and younger than 4 months old (n = 10). (1)HMRS were performed in all patients. [Phe](brain) were measured by absolute [Phe](brain) using Creatinine as an internal reference. [Phe](blood) were measured and developmental quotient (DQ) or intelligence quotients (IQ) were evaluated.
Result: (1) [Phe](brain) measured by (1)HMRS ranged from 0.0640 to 0.6296 (M = 0.1542) while the [Phe](blood) was from 0.3804 to 2.5140 mmol/L (M = 1.5210 mmol/L) in all the 32 cases of HPA patients. (2) There was a positive linear correlation (r = 0.6103 (P < 0.01)) between [Phe](blood) and [Phe](brain). And there were interindividual differences in [Phe](brain) in several patients. (3) Variable mental retardation were observed in 23/32 cases in this study. (4) There was a negative correlation between [Phe](blood) and [Phe](brain) to the mental retardation (r(blood) = -0.5045, r(brain) = -0.6471 (P < 0.01)) in 22 cases of the HPA patients older than 4 months. And [Phe](brain) had more significant correlation with mental development than [Phe](blood).
Conclusion: The [Phe](blood) could correspondingly represent the [Phe](brain) in most HPA patients. The Phe concentration could reflect the degree of mental retardation substantially in 22 cases with HPA older than 4 months. And the [Phe](brain) could more accurately illustrate it. (1)HMRS can be used to quantitate intracerebral Phe concentrations non-invasively in HPA patients. Preliminary findings suggest that interindividual variations in the kinetics of Phe uptake and metabolism do exist. (1)HMRS has great clinical significance in understanding the mechanism of HPA patient's mental retardation, providing proper objective standards for better diagnosis and treatment of HPA patients.