Shield J P, Wadsworth E J, MacDonald A, Stephenson A, Tyfield L, Holton J B, Marlow N
Institute of Child Health, St Michael's Hill, Bristol, UK.
Arch Dis Child. 2000 Sep;83(3):248-50. doi: 10.1136/adc.83.3.248.
To evaluate the cognitive outcome of a cohort of children with galactosaemia in relation to genotype.
The cohort was drawn from children notified to the British Paediatric Surveillance Unit galactosaemia study which ran from 1988 to 1990. Cognitive outcome was assessed using the Wechsler Intelligence Scale for Children or the Wechsler Preschool and Primary Scale of Intelligence. Parents completed a questionnaire detailing educational status, and the attending paediatrician returned a questionnaire regarding age at diagnosis and biochemical outcome over the previous two years.
A total of 45 children were genotyped: 30 were homoallelic for the Q188R mutation, the remainder being heteroallelic for Q188R with K285N (n = 4), L195P (n = 4), or other mutations (n = 7). Psychometric evaluation was available in 34 cases: mean full scale IQ was 79, verbal quotient 79, and performance quotient 82. Genotype was not related to galactose-1-phosphate (Gal-1-P) concentrations. However, children homoallelic for the Q188R mutation had significantly lower IQ scores than those who were heteroallelic (73. 6 v 94.8). This difference was independent of social and demographic influences and Gal-1-P concentrations over the previous two years.
In children with galactosaemia, cognitive outcome appears to relate to genotype rather than metabolic control, as reflected by Gal-1-P concentrations. The value of measuring Gal-1-P concentrations routinely once successfully established on a galactosaemia diet is questionable as concentrations do not appear to affect outcome. In the UK population, homozygosity for the Q188R mutation is invariably associated with a poor outcome, and there is evidence that variability in neurocognitive outcome is at least part dependent on allelic heterogeneity.
评估一组半乳糖血症患儿的认知结局与基因型的关系。
该队列来自于1988年至1990年向英国儿科监测单位报告的半乳糖血症研究中的儿童。使用韦氏儿童智力量表或韦氏学前及初小儿童智力量表评估认知结局。家长填写一份详细说明教育状况的问卷，主治儿科医生返回一份关于诊断年龄和前两年生化结局的问卷。
共对45名儿童进行了基因分型：30名儿童为Q188R突变的纯合等位基因，其余儿童为Q188R与K285N（n = 4）、L195P（n = 4）或其他突变（n = 7）的杂合等位基因。34例有心理测量学评估结果：平均全量表智商为79，言语商数为79，操作商数为82。基因型与1-磷酸半乳糖（Gal-1-P）浓度无关。然而，Q188R突变纯合等位基因的儿童智商得分显著低于杂合等位基因的儿童（73.6对94.8）。这种差异独立于社会和人口统计学影响以及前两年的Gal-1-P浓度。
在半乳糖血症患儿中，认知结局似乎与基因型而非代谢控制有关，这一点由Gal-1-P浓度反映出来。一旦成功建立半乳糖血症饮食，常规测量Gal-1-P浓度的价值值得怀疑，因为浓度似乎不影响结局。在英国人群中，Q188R突变的纯合性总是与不良结局相关，并且有证据表明神经认知结局的变异性至少部分取决于等位基因异质性。
