MATERNAL PROPIONIC AND METHYLMALONIC ACIDEMIA. HOW SHOULD FOLLOW UP BE DURING PREGNANCY? Bueno Delgado MA 1 , Delgado Pecellín C 1 , Lage S 2 , García Valdecasas MS 1 , Pérez Pérez M 1 1 Div Metab Dis, V. Rocio,Univ Child Hosp, Sevilla, Spain 2 Div Metab, Cruces Hosp, Barakaldo, Spain Background: Present experience in diagnosis and treatment of the organic acidemias and all Inherited Metabolic Diseases, has allowed that women, with these pathologies, consider being mothers. Fear of possible descompensations during pregnancy and/or childbirth, and the ignorance of sanitary personnel involved in the care of the patient, generates great anxiety to the patient in consdiering having a child. We report 3 successful pregnancies in women with organic acidemias. Methods: During each pregnancy profiles of amino acids, acylcarnitines, carnitine in plasma and organic acids in urine were performed. Patients sent samples of dry blood weekly for determination of amino acids and acylcarnitines and monthly for obstetric and diet evaluation and determination of urine organic acids. Results: We observed a great decrease of propionylcarnitine and total canitine. Oral carnitine supplement was required in three pregnancies. We also observed a decrease in maternal essential amino acids, but restricted protein diet was necessary all through the pregnancy. Changes in organic acids were not observed. Conclusions: We have observed a distinctive but common metabolic profile in 3 pregnancies. An exhaustive control of amino acids, acylcarnitines, carnitine and organic acids and diet management is essential for a good outcome in maternal organic acidemias. Molybdenum cofactor is essential for sulphite oxidase and xanthine dehydrogenase activities; and its deficiency is usually associated with devastating neurological manifestations. Although milder cases with later onset have been identified, the classical presentations are often fatal in the early age. We present a follow-up case of 23-year-old Caucasian female who was diagnosed at 11 years of age following similar diagnosis made in her younger sibling [1] . Biochemical profiles of her blood and fibroblast were consistent with the diagnosis. This was subsequently confirmed with MOCS2 gene analysis which showed compound heterozygous mutations. Despite a strikingly abnormal initial brain imaging, she was otherwise asymptomatic apart for mild lenses dislocation. Up until recently, she led a normal healthy life with stable employment and fully independence. Following recent serial family bereavements, she presented to a local neurology department with dramatic deterioration. She has marked apathy, dysarthria, dysphagia, associated with generalised dystonia but preserved comprehension. Serial brain imaging reveals significant progression in basal ganglia abnormalities and white matter changes. This case illustrates the dilemma in managing asymptomatic individuals over a prolonged period in this extremely rare condition. Late-onset Tay-Sachs (LOTS) is an autosomal recessive, neurodegenerative, lysosomal storage disease, caused by deficiency of ß-hexosaminidase A (Hex A). In vitro and in vivo studies suggest that Hex A activity can be partially rescued by the drug pyrimethamine. Here, four adult patients with LOTS were treated with different regimen of pyrimethamine for a total of 24 months. In vitro tests in patient fibroblasts prior to treatment shown a good response with 79 to 189% increase in basal Hex A activity. In vivo treatment response was assessed by repeated measures of Hex A activity in leukocytes. Although Hex A increased in all patients during the first four months of treatment, mirrored by some clinical improvement, prolonged inhibitory effect was observed in all patients after this initial period of time. This inhibitory effect was not reversed by decreasing the dosage of pyrimethamine, but only when the drug was reintroduced after at least two weeks of wash out. Attempts to reintroduce the drug at lower dosage (25 mg/d) resulted in the same inhibitory effect after 2-3 months. Finally, a cycle with continuous treatment for two months (25 mg/d) followed by two weeks of wash out resulted in the most sustained response.