Prevention is the Best Therapy: The Geneticist's Approach.

Abstract During the last two decades prenatal genetic screening and diagnosis has become the cornerstone of medical care for family planning to prevent genetic disease. Carrier screening programs for genetic disorders that are prevalent in various populations identify couples and pregnancies at risk of having an affected child. These couples can proceed with a choice of invasive prenatal diagnosis tests of the fetus (chorionic villous sampling and amniocentesis), or non-invasive prenatal testing of free fetal DNA circulation in the maternal blood which has emerged within the last few years and is currently available for fetal sexing for X Linked disorders. Despite the advances in prenatal diagnosis, couples found to have a fetus affected with a genetic disorder may need to face the dilemma of pregnancy termination. Preimplantation genetic diagnosis (PGD) is an alternative to preempt risk of having a child affected with a life-altering genetic disorder. This technique allows biopsy and genetic diagnosis of embryos obtained from in vitro fertilization by analysis of the genetic material from one or a few embryonic cells. Only unaffected embryos are returned to the mother to establish the pregnancy. We present our experience using PGD for four Lysosomal storage disorders: Tay Sachs, Gaucher type 1, Hunter and Fabry disease with some of the couples being carriers of more than one genetic disorder. PGD is applicable to most disorders for which the gene and the familial mutation are known and should be presented to couples as an alternative to invasive prenatal testing.

Fabry disease: immunocytochemical characterization of neuronal involvement.

Fabry disease is an X-linked glycosphingolipid storage disease caused by deficiency of alpha-galactosidase. Storage of globotriaosylceramide, also known as ceramide trihexoside, is maximal in blood vessels but also occurs in neurons. We performed neuropathological histochemical studies on the brains and spinal cords of 2 patients with confirmed Fabry disease. Luxol fast blue-positive deposits were found in blood vessels throughout the central and peripheral nervous system and within selected neurons in spinal cord and ganglia, brainstem, amygdala, hypothalamus, and entorhinal cortex. Regions adjacent to involved neuronal groups, including nucleus basalis, striatum, globus pallidus, and thalamus, were spared. Electron microscopy showed lamellar cytoplasmic neuronal inclusion bodies. Using a monoclonal antibody reactive with ceramide trihexoside, we found more extensive neuronal deposition than evident by Luxol-fast blue staining and new areas of neuronal storage in the spinal cord and cerebral cortex. Blood vessels throughout the nervous system were strongly immunoreactive. The highly selective pattern of neuronal involvement we found suggests that glycosphingolipid exposure, uptake, or catabolism varies greatly with respect to neuronal morphology and distribution. The degree of toxicity to neurons and the clinical significance of this neuronal storage remains to be defined.