Molecular genetics of mucopolysaccharidosis type I: mutation analysis among the patients of the former Soviet Union.

Mucopolysaccharidosis type I (MPS-I) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of the lysosomal protein alpha-l-iduronidase (IDUA). Patients present within a broad spectrum of phenotypes from severe (Hurler syndrome) to clinically less severe (Scheie syndrome). Since 1982 a special program for the diagnosis and prevention of lysosomal storage diseases has operated in the former Soviet Union (FSU).

Postnatal and prenatal diagnosis of lysosomal storage diseases in the former Soviet Union.

Diagnosis and prevention of lysosomal storage diseases (LSD) in the former Soviet Union (FSU) is based on the interaction of various local counselling units with the Department of Inherited Metabolic Diseases (DIMD) at the Research Center of Medical Genetics (RAMS). Work began in 1982 using standard, as well as newly developed biochemical techniques. 25 different LSD were diagnosed in 445 patients from 404 families.

First-trimester enzyme exclusion of Farber disease using a micromethod with [3H]ceramide.

Farber disease was diagnosed in a patient with typical features and ceramide accumulation in lipogranulomatous nodules. [3H]Ceramide with high specific activity was prepared and used to confirm diagnosis in the patient after her death and for prenatal studies in this family. A micromethod was developed for ceramidase assay in chorionic villi.

Four novel mutant alleles of the arylsulfatase B gene in two patients with intermediate form of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).

Mucopolysaccharidosis type VI (MPSVI, Maroteaux-Lamy syndrome) is a lysosomal storage disease for which multiple clinical phenotypes have been described. A deficiency of the enzyme arylsulfatase B (ASB, N-acetylgalactosamine-4-sulfatase) is the cause of this autosomal recessively inherited disorder. The genotypes of two patients with an intermediate form of MPSVI have been determined by polymerase chain reaction (PCR) amplification of the entire open reading frame of the ASB gene and subsequent direct sequencing of both strands of the PCR fragments by an automated nonradioactive approach.

High-resolution loading tests in the study of genetic heterogeneity in gangliosidosis fibroblasts.

GM1- and GM2-gangliosides were isolated from brain and radiolabelled. The labelled moieties were localized by hydrolysis with lysosomal enzymes, followed by thin-layer chromatography of the products. High-resolution loading tests with labelled gangliosides were developed and found to differentiate infantile and juvenile forms of GM1- and GM2-gangliosidoses as well as the identification of B, O and AB types of GM2-gangliosidosis.

Distribution of Gd- alleles in some ethnic groups of the USSR.

A population study of Gd- allele distribution was made in similar (age-sex) samples of schoolchildren and students from different ethnic groups: Russians, Ashkenazi Jews, and Azerbaijanians. Both the frequency and the spectrum of the Gd- alleles were quite different. The Gd- frequency in Russians (Kostroma region) was 0.