RESUMEN
Introducción: El síndrome Sly (MPS VII) (MIM #2532209), es una enfermedad autosómica recesiva con afección multisistémica, grave y progresiva, caracterizada por presencia de hidrops fetal dentro de su espectro clínico. Es ocasionada por deficiencia de la enzima β-glucuronidasa codificada por el gen GUSB (7q11.21), cuya función es degradar dermatán-sulfato, condroitin-sulfato y heparán-sulfato. Se considera de las MPS menos frecuentes, con incidencia 1:2,000,000 recién nacidos vivos y 200 casos reportados a la fecha. Objetivo: Realizar el primer estudio en México para describir características sociodemográficas, clínicas y moleculares de pacientes con MPS VII. Material y Métodos: Previa autorización del Comité en Ética e Investigación, se realizó un estudio retrospectivo, transversal, multicéntrico de los pacientes con MPS VII diagnosticados en México. El análisis descriptivo de todas las variables encontradas se realizó mediante Excel y SPSS. Resultados: Se incluyeron 13 pacientes de 7 estados del país con MPS VII, detectándose 53.84% mujeres, con relación 1.16 mujeres: 1 hombre; 30.76% finados; edad promedio 11.4 años (rango 1-20 años); edad promedio diagnóstico 7.9 años (rango 2 meses -15 años); 30.76% consanguinidad, 30.76% endogamia, 38.46% antecedente de abortos en los padres, 53.80% hidrops fetal, 100% facies tosca, 75% discapacidad intelectual, 53.84% hepatoesplenomegalia, 46.15% opacidad corneal, 100% epicanto, 38.46% valvulopatía cardiaca, 61.53% talla baja, 100% con actividad enzimática baja, 53.84% presentaron la variante c.526C>T y se reportaron las variantes c.308G>A, c.383C>T, c.1192C>T, c.1222C>T, c.1232G>, c.1244C>T, c.1742T>C. Ningún paciente cuenta con trasplante de células madre y 30.76% se encuentran en terapia enzimática. Conclusiones: Primer estudio en describir características clínicas, bioquímicas y moleculares de 13 pacientes con MPS VII en México. Los hallazgos clínicos concuerdan con lo reportado en la literatura, ya que la facies gruesa, macrocefalia, cuello corto, puente nasal deprimido, pelo áspero, cejas pobladas, dientes espaciados, pectum carinatum, hepatomegalia, talla baja, disostosis múltiple, contracturas articulares, pérdida de amplitud de los movimientos y alteraciones neurológicas representan el mayor porcentaje del fenotipo característico de esta entidad; excepto mano en garra, disostosis múltiple y epicanto.
Palabras clave: MPS VII, Síndrome Sly, β-glucuronidasa, GUSB
ABSTRACT
Background: Sly syndrome (MPS VII) (OMIM #2532209), is an autosomal recessive disease with multisystem, severe and progressive disease, characterized by the presence of fetal hydrops within its clinical spectrum. It is caused by deficiency of the enzyme β-glucuronidase encoded by the GUSB gene (7q11.21), responsible for degrading dermatan-sulfate, chondroitin-sulfate and heparan-sulfate. It is considered one of the least frequent MPS, with incidence 1:2,000,000 live births and 200 cases reported to date. Objective: To conduct the first study in Mexico to describe sociodemographic, clinical and molecular characteristics of patients with MPS VII. Material and Methods: With the prior authorization of the Ethics and Research Committee, a retrospective, cross-sectional, multicenter study of patients with MPS 7 diagnosed in Mexico was conducted. The descriptive analysis of all the variables found was performed using Excel and SPSS. Results: A total of 13 patients from 7 states of the country with MPS VII were included, 53.84% of whom were women, with 1.16 women: 1 man; 30.76% deceased; mean age 11.4 years (range 1-20 years); mean age diagnosis 7.9 years (range 2 months -15 years); 30.76% consanguinity, 30.76% inbreeding, 38.46% history of parental miscarriages, 53.80% fetal hydrops, 100% facies tosca, 75% intellectual disability, 53.84% hepatosplenomegaly, 46.15% corneal opacity, 100% epicanthus, 38.46% valvular disease, 61.53% were short in stature, 100% had low enzyme activity, 53.84% had the c.526C>T variant and the variants c.308G>A, c.383C>T, c.1192C>T, c.1222C>T, c.1232G>, c.1244C>T, c.1742T>C. No patient has a stem cell transplant and 30.76% are on enzyme therapy.Conclusions: This is the first study to describe the clinical, biochemical and molecular characteristics of 13 patients with MPS VII in Mexico. The clinical findings are consistent with what has been reported in the literature, as the gross facies, macrocephaly, short neck, depressed nasal bridge, coarse hair, bushy eyebrows, spaced teeth, pectum carinatum, hepatomegaly, short stature, multiple dysostosis, joint contractures, loss of range of motion and neurological alterations represent the largest percentage of the characteristic phenotype of this entity; except clawed hand, multiple dysostosis and epicanthus.
Key words: MPS VII, Sly syndrome, β-glucuronidase, GUSB
