Congenital ocular malformations (lens subluxation, pupillary displacement, cataract, myopia) and classic galactosaemia associated with Q188R and /or G1391A mutations

. Purpose: 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. Methods: 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). Results: 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 luxa‐tion, 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. Conclusions: 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