Sistatyonin Beta-Sentaz Eksikliğine Bağlı Homosistinüri Hastalarında Klinik, Biyokimyasal, Moleküler Bulguların Belgelenmesi ve Genotip-Fenotip Ilişkisinin Araştırılması

Abstract

Hospital files of cystathionine beta-synthase (CBS) deficiency patients were reviewed retrospectively. Twenty-six patients from 20 families were diagnosed between 1981-2012. Patients were reviewed under three clinical groups: 46.2% neurological (mental retardation), 23.1% thrombosis (thromboembolic; TE event) and 19.2% connective tissue (normal IQ, without thrombosis). Median ages at diagnosis were 8 years, being higher in thrombosis (10 years) and connective tissue (11 years) groups than the neurological group (7.5 years). Mental retardation (77%), lens ectopia (77%), osteopenia (58%), marfanoid features (54%), psychiatric disorders (27%), TE events (23%), seizures (23%), epilepsy (15%), mitral valve prolapsus (15%), pectus excavatum (11%) were the major clinical findings. Half of the patients (54%) were pyridoxine responsive. All of the pyridoxin non-responsive patients were mentally retarded. A patient was diagnosed while he was investigated for hepatosteatosis. Another patient has presented with diabetic ketoacidosis, which was a novel association. A newborn with Rh isoimmunization was diagnosed through selective screening at hospital. Two patients were complicated with severe megaloblastic anemia due to folate depletion. Factor V Leiden (n=1), low ATIII and high Factor VIII levels (n=2) were detected in thrombosis group. A total of 17 different CBS mutations, four being novel, were detected. Novel CBS mutations were p.Asn93Tyr, p.Leu251Pro, IVS7-2A>T, and p.Asp281Val. Mutation p.Gly259Ser was the most common (%15) detected primarily in neurological group, while p.Gly85Arg, p.Arg125Trp, p.Pro145Leu, p.Ile278Thr, p.Ser349Asn were detected in the thrombosis group. The distribution of MTHFR c.677C>T, MTHFR c.1298G>A and PAI-I 4G/5G was not different between groups. New TE events were not reported throughout a 190 patient-years follow-up period. One patient has developed leukoencephalopathy following betaine treatment.