2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-MEXICAN CLINICAL AND MOLECULAR REGISTRY OF MUCOPOLYSACCHARIDOSIS TYPE VII

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The Mexican Clinical and Molecular Registry of Type VII Mucopolysaccharidosis (MPS VII) is described in this document. MPS VII, also known as Sly syndrome, is a severe and progressive autosomal recessive disease caused by mutations in the GUSB gene, resulting in β-glucuronidase deficiency. The accumulation of abnormal glycosaminoglycans (GAGs) in lysosomes leads to cellular malfunction in different tissues. MPS VII can present as a severe early-onset disease or a milder late-onset phenotype with normal or near-normal intelligence. This study aims to describe the sociodemographic, clinical, and molecular characteristics of the first Mexican patient registry for MPS VII.<br /><br />The study conducted a retrospective, cross-sectional, multicenter analysis of MPS VII patients in Mexico. Excel and SPSS were used for descriptive analysis. The results show that MPS VII is a rare disease, with an incidence of 1:2,000,000 live births and approximately 200 reported cases to date. The registry includes 11 patients, with a sex ratio of 1.7:1 and an age range of 4-20 years. The age at diagnosis ranged from 2 days to 13 years.<br /><br />Some notable findings from the registry include two families with consanguinity and a history of recurrent abortions, with fetal hydrops diagnosis. Despite some patients being described as having "claw hand," radiographs did not show the characteristic dysostosis seen in other forms of mucopolysaccharidoses. The phenotype observed in the hand may be a neurological symptom rather than a skeletal deformity.<br /><br />Mutations found in the patient cohort included c.526C>T (54.5%), c.308G>A, c.383C>T, c.1192C>T, c.1222C>T, c.1232G>, c.1244C>T, and c.1742T>C. None of the patients have undergone stem cell transplantation, and only three are on enzyme therapy. The rest are awaiting a decision from their hospital Ethical Committee regarding a compassionate therapy program, as enzyme replacement therapy has not been approved by the Mexican Secretary of Health.<br /><br />Common clinical features observed in the registry include fetal hydrops, coarse facies, intellectual disability, hepatosplenomegaly, corneal opacity, and short stature. However, it is noted that the dysmorphology observed in the hand may be a neurological symptom rather than a skeletal deformity.<br /><br />The study aims to expand knowledge about clinical and molecular variability in MPS VII and hopes that the information provided will contribute to timely diagnosis and management in Mexico and other populations.

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Presenting Author - Ma Dolores Hernandez, MD, PhD; Co-Author - Jaime Asael Lopez Valdez, Dr, Clinical Geneticist; Co-Author - Cristian Mauritanya Muñoz Sánchez, Dr, Pediatrician; Co-Author - Estefania Duran Sanchez, Medical student; Co-Author - Maria Angelica Ramirez Hernandez, Dra, Master in Genetics; Co-Author - Alma Delia Vázquez de la Serna, Dr, Pediatrician; Co-Author - Adriana Ruiz Herrera, Dr, Clinical Geneticist; Co-Author - Claudia Rivera Acuña, Dr, Pediatrics Neurologist; Co-Author - Beatriz Adriana Llamas Guillen, Dr, Pediatrician; Co-Author - Luz María Sánchez Sánchez, Dr, Pediatric Neonatologist; Co-Author - Alondra Deras Martínez, Dr, Pediatrics Neurologist; Co-Author - Carmen Amor Avila Rejón, Dr, Clinical Geneticist; Co-Author - José Elias García Ortíz, Dr, Clinical Geneticist; Co-Author - Laura Flores, Dra, Clinical Geneticist;

Meta Tag

Biochemical genetics

Clinical History

Delineation of Diseases

Genotype-Phenotype Correlations

Metabolic Disorder

Natural History

Phenotypic delineation of disorders

Co-Author Jaime Asael Lopez Valdez, Dr, Clinical Geneticist

Co-Author Cristian Mauritanya Muñoz Sánchez, Dr, Pediatrician

Co-Author Estefania Duran Sanchez, Medical student

Co-Author Maria Angelica Ramirez Hernandez, Dra, Master in Genetics

Co-Author Alma Delia Vázquez de la Serna, Dr, Pediatrician

Co-Author Adriana Ruiz Herrera, Dr, Clinical Geneticist

Co-Author Claudia Rivera Acuña, Dr, Pediatrics Neurologist

Co-Author Beatriz Adriana Llamas Guillen, Dr, Pediatrician

Co-Author Luz María Sánchez Sánchez, Dr, Pediatric Neonatologist

Co-Author Alondra Deras Martínez, Dr, Pediatrics Neurologist

Co-Author Carmen Amor Avila Rejón, Dr, Clinical Geneticist

Co-Author José Elias García Ortíz, Dr, Clinical Geneticist

Co-Author Laura Flores, Dra, Clinical Geneticist

Presenting Author Ma Dolores Hernandez, MD, PhD

Keywords

Mexican Clinical and Molecular Registry

Type VII Mucopolysaccharidosis

MPS VII

Sly syndrome

GUSB gene

β-glucuronidase deficiency

abnormal glycosaminoglycans

lysosomes

early-onset disease

late-onset phenotype