The Manton Center for Orphan Disease Research, Division of Genetics, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Mol Genet Metab. 2012 May;106(1):7-11. doi: 10.1016/j.ymgme.2012.03.007. Epub 2012 Mar 21.
Classic galactosemia is an autosomal recessive disorder of carbohydrate metabolism, due to a severe deficiency of the enzyme, galactose-1-phosphate uridyltransferase (GALT), that catalyzes the conversion of galactose-1-phosphate and uridine diphosphate glucose (UDPglucose) to uridine diphosphate galactose (UDPgalactose) and glucose-1-phosphate. Upon consumption of lactose in the neonatal period, the affected infants develop a potentially lethal disease process with multiorgan involvement. Since the advent of newborn screening (NBS) for galactosemia, we rarely encounter such overwhelmingly ill newborns. After ascertainment that the positive NBS indicates the possibility of galactosemia due to GALT deficiency, the critical question for the physician is whether the infant has the classic or a variant form of GALT deficiency, as classic galactosemia is a medical emergency. However, there are over 230 GALT gene mutations that have been detected around the world. Yet, most positive NBS tests are due to the Duarte biochemical variant condition or a simple false positive. In order to make the correct decision as well as provide informative counseling to parents of infants with a positive NBS, I utilize a relatively simple classification scheme for GALT deficiency. There are three basic forms of GALT deficiency: 1) classic galactosemia; 2) clinical variant galactosemia; and 3) biochemical variant galactosemia. The classic genotype is typified by Q188R/Q188R, the clinical variant by S135L/S135L and the biochemical variant by N314D/Q188R. In classic galactosemia, the erythrocyte GALT enzyme activity is absent or markedly reduced, the blood galactose and erythrocyte galactose-1-phosphate levels are markedly elevated, and the patient is at risk to develop potentially lethal E. coli sepsis, as well as the long-term diet-independent complications of galactosemia. Patients with the clinical variant form require treatment but do not die from E. coli sepsis in the neonatal period. If the clinician suspects galactosemia, even if based on clinical findings alone, then the infant should be immediately placed on a lactose-restricted diet. The purpose of this review is to help the clinician make the correct therapeutic decision after an NBS test has returned positive for galactosemia.
经典型半乳糖血症是一种常染色体隐性遗传性碳水化合物代谢紊乱，由酶半乳糖-1-磷酸尿苷酰转移酶（GALT）严重缺乏引起，该酶催化半乳糖-1-磷酸和尿苷二磷酸葡萄糖（UDPglucose）转化为尿苷二磷酸半乳糖（UDPgalactose）和葡萄糖-1-磷酸。在新生儿期摄入乳糖后，受影响的婴儿会出现多器官受累的潜在致命疾病过程。自从新生儿筛查（NBS）用于半乳糖血症以来，我们很少遇到如此病重的新生儿。在确定阳性 NBS 表明由于 GALT 缺乏而有可能发生半乳糖血症后，医生的关键问题是婴儿是否患有经典或变异形式的 GALT 缺乏症，因为经典半乳糖血症是一种医疗急症。然而，全世界已经检测到超过 230 种 GALT 基因突变。然而，大多数阳性 NBS 测试是由于杜阿尔特生化变异情况或简单的假阳性。为了做出正确的决策，并为 NBS 阳性婴儿的父母提供信息丰富的咨询，我使用相对简单的 GALT 缺乏分类方案。GALT 缺乏症有三种基本形式：1）经典半乳糖血症；2）临床变异半乳糖血症；3）生化变异半乳糖血症。经典基因型以 Q188R/Q188R 为特征，临床变异型以 S135L/S135L 为特征，生化变异型以 N314D/Q188R 为特征。在经典半乳糖血症中，红细胞 GALT 酶活性缺失或明显降低，血液半乳糖和红细胞半乳糖-1-磷酸水平明显升高，患者有发生潜在致命性大肠杆菌败血症的风险，以及半乳糖血症的长期非饮食相关并发症。临床变异型患者需要治疗，但在新生儿期不会因大肠杆菌败血症而死亡。如果临床医生怀疑半乳糖血症，即使仅基于临床发现，也应立即让婴儿限制乳糖饮食。本综述的目的是帮助临床医生在 NBS 测试对半乳糖血症呈阳性后做出正确的治疗决策。
