University of Freiburg Eye Clinic (Universitäts-Augenklinik), Freiburg, Germany.
Acta Ophthalmol. 2011 Aug;89(5):489-94. doi: 10.1111/j.1755-3768.2009.01691.x. Epub 2010 Mar 10.
Observations of multiple ocular malformations together with heterozygosity for galactosaemia in siblings and homozygosity in one child are highly unusual. In these case histories, a series of investigations in one family are reported.
Members of a family of two brothers and one sister and their children were pre- and post-surgically examined over several years. Blood examination was carried out in a laboratory specializing in investigation into genetic diseases (Dr Podskarbi, Munich).
Two brothers and one sister suffered from cataract-induced visual deterioration at 38, 34 and 35 years of age, respectively. All three siblings reported having had bilateral poor vision since early childhood. The three siblings' parents had no congenital ocular malformations, nor was there any parental consanguinity. One child, the 10-year-old son of the 35-year-old sister, exhibited classic galactosaemia and normal ocular findings. This sister's other child was healthy. All three siblings presented congenital lens luxation, axial myopia, cataract and iridodonesis. In addition, the 34-year-old brother showed unilateral right corectopia and left coloboma adjacent to the optic disc. The 38-year-old brother revealed myopic fundus changes, but no coloboma. The three siblings experienced a distinct increase in visual acuity after cataract surgery. Both eyes of the patients were partially or distinctly amblyopic, respectively. We assume an autosomal-recessive transmission. Molecular genetic examination of the 10-year-old child with classic galactosaemia showed homozygosity for the mutation Q188R with a complete galactose-1-phosphate-uridyltransferase (GALT) deficiency. Because of his galactose-free diet, the child showed normal values for galactose-1-phosphate. The 35-year-old mother showed compound heterozygosity for Q188R and G1391A (D2/G). The 10-year-old boy's father also revealed heterozygosity for galactosaemia caused by GALT deficiency. The two children of the 38-year-old brother were heterozygous for G1391A. They did not show any clinical abnormality. None of the family members had clinical signs of Marfan's syndrome or homocysteinuria. The three siblings' parents were not consanguineous.
Patients with worsening cataracts occurring at a pre-senile age should be examined for galactosaemia. We describe for the first time the molecular genetic findings in congenital ectopia lentis et pupillae. Early treatment in conjunction with a galactose-free diet is mandatory in patients with galactosaemia. Members of a family with heterozygosity for galactosaemia should be advised to attend a human genetic consultation.
兄弟姐妹中同时存在多种眼部畸形和半乳糖血症杂合子，以及一个孩子纯合子的情况非常罕见。在这些病例中，报告了一个家庭的一系列调查。
对一个由两个兄弟和一个姐妹及其子女组成的家庭的成员进行了多年的术前和术后检查。血液检查在一家专门从事遗传疾病研究的实验室（慕尼黑的 Podskarbi 博士）进行。
两个兄弟和一个姐妹分别在 38、34 和 35 岁时因白内障导致视力恶化。这三个兄弟姐妹都报告说从小就有双侧视力不佳。这三个兄弟姐妹的父母没有先天性眼部畸形，也没有任何近亲结婚。一个孩子，即 35 岁姐妹的 10 岁儿子，患有典型的半乳糖血症和正常的眼部发现。这位姐妹的另一个孩子是健康的。这三个兄弟姐妹都有先天性晶状体脱位、轴性近视、白内障和虹膜后粘连。此外，34 岁的兄弟表现为单侧右眼中心异位和左侧视盘旁的视网膜缺损。38 岁的兄弟表现为近视性眼底改变，但没有视网膜缺损。这三个兄弟姐妹在白内障手术后视力明显提高。患者的双眼均分别部分或明显弱视。我们假设为常染色体隐性遗传。对患有典型半乳糖血症的 10 岁儿童进行分子遗传学检查显示，Q188R 突变纯合子，完全半乳糖-1-磷酸尿苷转移酶（GALT）缺乏。由于他的无半乳糖饮食，孩子的半乳糖-1-磷酸值正常。35 岁的母亲表现为 Q188R 和 G1391A（D2/G）的复合杂合子。10 岁男孩的父亲也表现为 GALT 缺乏引起的半乳糖血症杂合子。38 岁兄弟的两个孩子均为 G1391A 杂合子。他们没有任何临床异常。没有一个家庭成员有马凡综合征或高半胱氨酸尿症的临床体征。这三个兄弟姐妹的父母没有近亲结婚。
对于早发性白内障的患者，应检查是否患有半乳糖血症。我们首次描述了先天性晶状体异位和瞳孔的分子遗传学发现。对于半乳糖血症患者，早期治疗结合无半乳糖饮食是强制性的。对半乳糖血症杂合子的家庭成员，应建议他们进行人类遗传咨询。
