Waisbren Susan E, Prabhu Sanjay P, Greenstein Patricia, Petty Carter, Schomer Donald, Anastasoaie Vera, Charette Kalin, Rodriguez Daniel, Merugumala Sai, Lin Alexander P
Boston Children's Hospital, 1 Autumn Street, #525, Boston, MA, 02115, USA.
Harvard Medical School, Boston, MA, USA.
JIMD Rep. 2017;34:77-86. doi: 10.1007/8904_2016_11. Epub 2016 Sep 28.
Researchers hypothesized that in phenylketonuria (PKU) high brain phenylalanine (Phe) levels and low brain tyrosine (Tyr) levels affect neuropsychological functioning. However, traditional magnetic resonance spectroscopy (MRS) yielded uncertain results of brain Phe and could not adequately measure brain Tyr. This pilot study examined the potential of correlated spectroscopy (COSY) to quantify these biomarkers and explain variability in neuropsychological functioning.
Nine adults with early treated classic PKU received magnetic resonance imaging (MRI) with COSY and a battery of neuropsychological tests. Brain Phe and Tyr in parietal white matter (PWM) were compared to results in gray matter of the posterior cingulate gyrus (PCG).
Brain Phe ranged from 101 to 182 (mean = 136.76 ± 23.77) μmol/L in PCG and 76 to 185 (mean = 130.11 ± 37.88) μmol/L in PWM. Brain Tyr ranged from 4.0 to 7.4 (mean = 5.44 ± 1.01) μmol/L in PCG and 4.1 to 8.4 (mean = 5.90 ± 1.48) μmol/L in PWM. Correlation coefficients were largest for brain Phe PWM and measures of auditory memory (rho = -0.79), anxiety (rho = 0.79), and executive functioning (rho = 0.69). Associations were in the expected direction, with higher brain Phe and lower brain Tyr related to poorer functioning. The two participants with severe structural MRI abnormalities had low brain Tyr levels in PCG and 3/5 of the participants with moderate to severe MRI abnormalities had higher than average brain Phe levels.
COSY has the potential to quantify brain Phe and Tyr at low concentrations and in specific brain regions. In this pilot study, these biomarkers were associated with indices of neuropsychological functioning. Additional studies are needed to validate the COSY results.
研究人员推测，在苯丙酮尿症（PKU）中，大脑苯丙氨酸（Phe）水平升高和酪氨酸（Tyr）水平降低会影响神经心理功能。然而，传统的磁共振波谱（MRS）对大脑Phe的检测结果不确定，且无法充分测量大脑Tyr。这项初步研究探讨了相关波谱（COSY）量化这些生物标志物以及解释神经心理功能变异性的潜力。
9名早期接受治疗的经典型PKU成年患者接受了COSY磁共振成像（MRI）检查以及一系列神经心理测试。将顶叶白质（PWM）中的大脑Phe和Tyr与后扣带回皮质（PCG）灰质中的结果进行比较。
PCG中的大脑Phe浓度范围为101至182（平均 = 136.76 ± 23.77）μmol/L，PWM中的浓度范围为76至185（平均 = 130.11 ± 37.88）μmol/L。PCG中的大脑Tyr浓度范围为4.0至7.4（平均 = 5.44 ± 1.01）μmol/L，PWM中的浓度范围为4.1至8.4（平均 = 5.90 ± 1.48）μmol/L。大脑Phe PWM与听觉记忆指标（rho = -0.79）、焦虑指标（rho = 0.79）和执行功能指标（rho = 0.69）的相关系数最大。关联方向符合预期，大脑Phe水平越高、大脑Tyr水平越低，功能越差。两名患有严重结构MRI异常的参与者PCG中的大脑Tyr水平较低，五分之三患有中度至重度MRI异常的参与者大脑Phe水平高于平均水平。
COSY有潜力在低浓度和特定脑区量化大脑Phe和Tyr。在这项初步研究中，这些生物标志物与神经心理功能指标相关。需要进一步的研究来验证COSY的结果。
