RESUMEN
Basel-Vanagaite-Smirin-Yosef syndrome is a recently described autosomal recessive intellectual disability syndrome caused by variants in the MED25 gene. While it was originally identified in Brazil, it was further described in Israel by authors who are now the namesake of the condition. A 2018 publication further contributed to its delineation, but the patient's phenotype was complicated by a dual diagnosis. More recently, an article describing a set of affected siblings was published. We describe three, previously unreported, patients showing clinical variability for this newly defined syndrome. The major features determined by "reverse phenotyping" include significant to profound developmental delays/intellectual disability with absent or delayed speech, epilepsy, ocular abnormalities, cleft lip and/or palate, congenital heart disease, urogenital anomalies, skeletal abnormalities, brain malformations and/or microcephaly, failure to thrive, and dysmorphic features. The authors suggest the delineation of an acronym using the gene name and common features seen across the majority of patients reported so far. This new nomination, MED-DOCS, may help clinicians to recognize, suspect, and remember this novel syndrome.
Asunto(s)
Anomalías Múltiples/genética , Predisposición Genética a la Enfermedad , Discapacidad Intelectual/genética , Complejo Mediador/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/fisiopatología , Brasil/epidemiología , Preescolar , Labio Leporino/genética , Labio Leporino/fisiopatología , Femenino , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/fisiopatología , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/fisiopatología , Israel/epidemiología , Masculino , Microcefalia/diagnóstico , Microcefalia/genética , Microcefalia/fisiopatología , Fenotipo , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
We hypothesized that gut motility likely plays a critical role in the metabolic stability in propionic acidemia (PA). Therefore, 4 known patients with PA (aged 47 months to 185 months) were prospectively studied over 7 days in the Clinical Research Center at Children's Hospital, Boston. Determinations of ammonia, bicarbonate, and amino acids in blood; organic acids and propionylglycine in urine; and a lactulose breath test were conducted under two study conditions: on regular therapy (for 4 days) and on regular therapy plus Senekot (Purdue Frederick Company, Norwalk, Conn), an intestinal motility agent (for 3 days). The total gastrointestinal transit time was calculated using 20 nonabsorbable, inert, radio-opaque markers. The addition of an intestinal motility agent resulted in a significant decrease in blood ammonia, urinary excretion of propionylglycine, and a rise in the ratio of free to total carnitine over baseline. We concluded that enhancement of gut motility can improve metabolic stability in patients with PA.