RESUMO
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a low-prevalence pathology mainly associated with pathogenic variants of the UMOD gene. It is characterized by the progressive deterioration of renal function, associated with hyperuricemia and accompanied by a family history of gout or hyperuricemia. Often, clinical variability and a lack of molecular testing results in diagnostic failure to determine the ADTKD-UMOD association. Case presentation: We describe the case of a 14-year-old male who presented to the nephrology service with hyperuricemia, renal ultrasonographic changes, and progression to chronic kidney disease in 4 years. He had a family history of hyperuricemia. A probable genetic disease with an autosomal dominant inheritance pattern was considered, confirmed by the presence of a probably pathogenic variant of the UMOD gene, not previously reported in the literature. Conclusion: The investigation of this case led to the identification of a new variant in the UMOD gene, broadening the spectrum of known variants for ADTKD-UMOD. In addition, in this case, a comprehensive anamnesis, that takes into account family history, was the key point to carry out genetic tests that confirmed the diagnosis suspicion. Directed Genetic tests are currently an essential diagnostic tool and should be performed as long as they are available and there is an indication to perform them.
Assuntos
Gota , Hiperuricemia , Doenças Renais Policísticas , Masculino , Humanos , Adolescente , Uromodulina , Gota/genética , Testes Genéticos/métodos , Doenças Renais Policísticas/genética , MutaçãoRESUMO
El Síndrome de Mowat - Wilson (SMW), es una rara enfermedad genética con prevalencia desconocida, hasta el año 2010 habían sido descritos 180 casos en la literatura mundial indexada. Los pacientes con SMW presentan un fenotipo característico dado por: frente amplia y abombada, hipoplasia mediofacial, hipertelorismo ocular, nariz y columnela prominentes, asociado a compromiso neurológico (epilepsia, retardo en neurodesarrollo y mental) y enfermedad de Hirschsprung, que ha sido descrita solo en algunos casos. (1,2) El SMW se origina por mutaciones puntuales en el gen ZEB2 y hasta en el 17% de los casos se presenta por deleciones submicroscópicas que comprometen la región cromosómica 2q22.3 donde se localiza este gen (3). El gen ZEB2 es determinante en la diferenciación de las células derivadas de la cresta neural y sistema nervioso central lo cual explicaría el fenotipo neurológico. Los autores describimos el primer caso de SMW en población Colombiana, causado por microdeleción de novo de la región cromosómica 2q22.2, resaltando así la importancia de un completo estudio citogenético molecular para pacientes con alta sospecha de síndromes de microdeleción (1,3).
Mowat Wilson Syndrome (MWS), is a rare disease the prevalence is currently unknown approximately 180 cases had been reported until 2010. MWS patients exhibit a characteristic phenotype given by, high forehead, frontal bossing, midface hypoplasia, ocular hypertelorism, prominent nose and columella associated with neurological involvement (epilepsy and moderate to severe intellectual deficiency) and Hirschsprung disease, which has been described only in some cases (1,2). MWS is caused by mutations in the gene ZEB2 and up to 17% of the cases presented by submicroscopic deletions that compromise 2q22.3 chromosomal region where this gene is located (3). ZEB2 is critical for the differentiation of cells derived from the neural crest and central nervous system which would explain the neurological phenotype. We describe the first case of MWS in Colombian caused by de novo microdeletion of chromosome 2q22.2 region, We highlighted the importance of a complete cytogenetic and molecular study in patients with high suspected of microdeletion syndromes (1,3).