RESUMEN
BACKGROUND: Activin A has been shown to enhance osteoclast activity and its inhibition results in bone growth. The potential role of activin A as a marker of chronic kidney disease-mineral bone disease (CKD-MBD) and its relationship with other markers has not been studied in children with CKD. METHODS: A cross sectional study was conducted among 40 children aged 2 to 18 years with CKD (Stage 2 to 5; 10 in each stage) and 40 matched controls. Activin A, cathepsin K, FGF-23, PTH, serum calcium, phosphorous and alkaline phosphatase in both groups were measured and compared. The correlation of activin A and markers of CKD-MBD was studied. A p value of < 0.05 was considered significant. RESULTS: The mean age of children with CKD was 9.30 ± 3.64 years. Mean levels of activin A in cases were 485.55 pg/ml compared to 76.19 pg/ml in controls (p < 0.001). FGF-23 levels in cases were 133.18 pg/ml while in controls it was 6.93 pg/ml (p < 0.001). Mean levels of cathepsin K were also significantly higher in cases as compared to controls. There was a progressive increase in activin A and cathepsin K levels with increasing stage of CKD. Activin A had a significant positive correlation with serum creatinine (r = 0.51; p < 0.001). CONCLUSIONS: Activin A levels progressively rise with advancing CKD stage. These findings suggest that activin A can be a potential early marker of CKD-MBD in children.
Asunto(s)
Activinas , Biomarcadores , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos , Insuficiencia Renal Crónica , Humanos , Niño , Activinas/sangre , Factor-23 de Crecimiento de Fibroblastos/sangre , Biomarcadores/sangre , Femenino , Estudios Transversales , Masculino , Adolescente , Preescolar , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Factores de Crecimiento de Fibroblastos/sangre , Catepsina K/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/diagnóstico , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/etiología , Estudios de Casos y Controles , Hormona Paratiroidea/sangre , Calcio/sangre , Fosfatasa Alcalina/sangre , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/diagnósticoRESUMEN
TRAPPC4-related neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (MIM# 618741) is a recently described TRAPPopathy with clinical findings of developmental delay, seizures, postnatal microcephaly, spasticity, facial dysmorphism, and cerebral and cerebellar atrophy. Muscle involvement, a frequent finding in TRAPPopathies, was observed in one individual with TRAPPC4-related disorder previously. Only a single variant, an in-frame deletion in one family has been reported outside a recurrent disease-causing variant. We report three individuals from two Indian families harboring novel bi-allelic missense variants c.191T>C and c.278C>T (NM_016146.6) in TRAPPC4 with classic clinical presentation in one and milder and later onset in the other family. We provide further evidence for muscle involvement and review the detailed phenotypic findings in individuals reported with this disorder till date.