Okur I 1 , Aydin HI 1 , Akin R 2 1 Div Metab Dis, Dep Ped, Gulhane MMF, Ankara, Turkey 2 Div Ped Neu, Dep Ped, Gulhane MMF, Ankara, Turkey Background: Hexosaminidase A deficiency results in a group of inherited neurodegenerative disorders characterized by impaired lysosomal catabolism of ganglioside GM2. Tay Sachs disease corresponds to deficiency of the alpha-subunit of beta-hexosaminidase. The infantile form of Tay-Sachs disease presents with progressive weakness, loss of motor skills, decreased attentiveness, and increased startle response beginning between three and six months of age with progressive evidence of neurodegeneration. More than 100 mutations have been described in HEXA gene which encodes the alpha subunit of beta-hexosaminidase. We here report a novel mutation in HEXA in a patient with infantile Tay-Sachs disease. Case Report: 34 month-old male patient, appeared to be completely normal at birth, presented with progressive weakness, severe psychomotor retardation, myoclonic jerks, an exaggerated startle reaction, and retinal cherry red spots. Leukocyte beta-hexosaminidase A activity in patient was profoundly low (1.72 nmol/h/mg protein of patient). The diagnosis of hexosaminidase A deficiency confirmed by a novel mutation (homozygote c.A1306G;I436V) in HEXA gene. Conclusions: The great majority of specific mutations described in the alpha subunit of the HEXA gene are associated with the acute infantile form. We here report a novel mutation associated with infantile form of Tay-Sachs disease. Background: Inborn errors of sialic acid metabolism include three lysosomal storage disorders: sialic acid storage disease (SASD), sialidosis and galactosialidosis. The phenotypical spectrum of these three diseases ranges from severe forms, which may present as hydrops fetalis, to relatively mild forms. Screening can be performed by determination of free (FSA) and conjugated (CSA) sialic acid in urine or amniotic fluid supernatant (AFS). Diagnosis of SASD can be performed by quantification of FSA in cultured fibroblasts. Objective: To develop simple quantitative procedures to determine FSA as well as CSA in AFS, and FSA in cultured fibroblasts, using isotope dilution LC-MS/MS. Results: In 6 SASD AFS samples FSA was 2-9-fold elevated compared to normal controls. CSA levels in AFS of 3 sialidosis and 4 galactosialidosis cases were all higher than the reference samples. The method was also validated for determination of FSA in fibroblast homogenates. In SASD fibroblasts FSA was clearly elevated compared to normal controls. Conclusion: We report simple quantitative procedures to determine FSA and CSA in AFS as well as FSA in fibroblasts, improving both prenatal diagnostic efficacy for sialic acid disorders and confirmatory testing in cultured fibroblasts following initial screening in urine or AFS. Introduction: α-Mannosidosis is a rare lysosomal storage disorder caused by deficiency of α-mannosidase. Characteristic symptoms of a-Mannosidosis are hearing loss in early childhood, skeletal abnormalities, immunodeficiency and mental retardation. Patients and Results: We investigated 31 patients, aged 3-44 years, with a-Mannosidosis. Common mutations found in 28 non-related patients were c.2248 C>T (9/ 56) and c.1830+1 G>C (6/56) in homozygous or heterozygous form. Mean age of onset was 1.5 years. Diagnosis was confirmed on average with 6.4 years. Most common first symptom was hearing loss, followed by skeletal abnormalities and development delay. Patients suffer from recurrent infections of upper airways in childhood and purulent infections of teeth and skin. 30 patients developed ataxia. 10 patients need a wheelchair. 6 patients showed psychiatric symptoms. Inguinal or umbilical hernia, mental retardation, amblyopia, gingivahyperplasia, mild hepatomegaly or splenomegaly can also be found in patients with a-Mannosidosis. Conclusion: Combination of hearing loss, recurrent infections, skeletal abnormalities and development delay are characteristic manifestations of a-Mannosidosis. A phase II-trial with enzyme replacement therapy for a-Mannosidosis is currently in process. Experience with other enzyme replacement therapies revealed that early diagnosis is important for efficacy of this therapy.