Sanfilippo A Syndrome Genetic Studies in the Patient from Azerbaijan Republic

Abstract

First time in the patient from Azerbaijan Republic, genetics of Mucopolysaccharidosis Type III - Sanfilippo A syndrome was identified and studied. In order to study Sanfilippo A genetics, authors used complex of modern molecular-genetic methods and techniques. During patient’s medical-genetic consultation with doctor pediatrician and doctor geneticist in the Central Hospital of Gyanja City, a patient, originated from Lachin region of the Republic, was identified as an affected one relied on the clinical manifestations. Parents had a consanguineous marriage first cousins. Clinical studies showed cognitive changes, speech disorder, aggressiveness, hyperactivity, autistic signs, troubles in motions, hepatomegaly, failure in gaining weight, and physical development lag. For diagnostics capillary and venous blood samples were used. Blood from the patient was sampled into 2 ml-tubes with anticoagulant and absorbed to DBS (Dry Blood Spot) cards. Urine analysis was carried out with thin-layer chromatography. Enzyme activity was valued with mass spectrometry technique, and the DNA level analysis for SGSH gene was conducted with NGS technique. Urine analysis results allowed us to diagnose provisionally Sanfilippo syndrome MPS III based on increased values of heparan sulfate and keratan sulfate. Specification of Sanfilippo syndrome type (A, B, C or D) was conducted with activity evaluation of all four lysosomal enzymes: N-sulfoglucosamine sulfohydrolase (for TypeА), alpha-N-acetyl-D-glucosea-minidase (for Type В), heparan acetyl-CоА-glucoseaminide-N-acetyltransferase (for Type C), N-acetylglucoseamine-6-sulfatase (for Type D). We have got N-sulfoglucosamine sulfohydrolase 0 activity specific for Sanfilippo А syndrome. Molecular analysis identified mutation c.7_16del, р.Cys3ProfsTer8 of SGSH gene: (NM_000199.5) in homozygous state. Taking into account reproductive age of parents, fetus prenatal diagnostics is being planned for the next pregnancies.