ABSTRACT
Cerebrotendinous xanthomatosis (CTX) is an uncommon autosomal recessive disease caused by deficiency of 27-sterol-hydroxylase that results in an accumulation of cholestanol in the central nervous system, eyes, tendons, and blood vessels. We report a 22-year-old woman with a history of cataract surgery at the age of 14, cholecystectomy due to cholelithiasis at the age of 17 and chronic diarrhea, who presented with a six months period of gait instability and frequent falls. Physical examination revealed a bilateral pyramidal and cerebellar syndrome, with no visible tendon xanthomas. Cerebral magnetic resonance imaging showed an increase of the signal intensity on the T2-weighted images in periventricular cerebral white matter, dentate nuclei and spinal cord. With a high suspicion of CXT, a genetic study was conducted identifying a pathogenic variant in the CYP27A1 gene. There is considerable variation in clinical characteristics and age of onset of this disease, including absence of tendon xanthomas, delaying the diagnosis. Early recognition and chronic chenodeoxycholic acid therapy can improve outcome and quality of life.
Subject(s)
Humans , Female , Young Adult , Chenodeoxycholic Acid/therapeutic use , Xanthomatosis, Cerebrotendinous/drug therapy , Xanthomatosis, Cerebrotendinous/diagnostic imaging , Vitamin D/therapeutic use , Magnetic Resonance Imaging , Cholestanol/blood , Xanthomatosis, Cerebrotendinous/genetics , Early Diagnosis , Cholestanetriol 26-Monooxygenase/geneticsABSTRACT
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease, caused by genetic deficiency of the 27-hydroxylase enzyme (encoded by CYP27A1). It plays a key role in cholesterol metabolism, especially in bile acid synthesis and in the 25-hydroxylation of vitamin D3 in the liver. Its deficiency causes reduced bile acid synthesis and tissue accumulation of cholestanol. Clinical manifestations are related to the presence of cholestanol deposits and include tendon xanthomas, premature cataracts, chronic diarrhea, progressive neurologic impairment and less frequently coronary heart disease, early onset osteoporosis and abnormalities in the optic disk and retina. An early diagnosis and treatment with quenodeoxycholic acid may prevent further complications, mainly neurological manifestations. This review summarizes cholesterol metabolism related to bile acid synthesis, physiopathology, biochemistry and treatment of cerebrotendinous xanthomatosis.
Subject(s)
Humans , Xanthomatosis, Cerebrotendinous , Chenodeoxycholic Acid/therapeutic use , Early Diagnosis , Xanthomatosis, Cerebrotendinous/diagnosis , Xanthomatosis, Cerebrotendinous/drug therapy , Xanthomatosis, Cerebrotendinous/genetics , Xanthomatosis, Cerebrotendinous/physiopathologyABSTRACT
La xantomatosis cerebrotendinosa (XCT) es un raro desorden del almacenamiento de los lípidos, que se transmite en forma autosómica recesiva y se caracteriza por el depósito de colesterol y colestanol en diferentes tejidos, con preferencia por los tendones, los cristalinos y el sistema nervioso central. El diagnóstico de la enfermedad se confirma con la presencia de βcolestanol en sangre y de alcoholes biliares en orina. Obedece a una mutación del gen CYP27A1 (responsable de la síntesis de la enzima esterol 27-hidrolasa) que mapea en el brazo largo del cromosoma 2. Se manifiesta clínicamente por un deterioro neurológico progresivo, además de la presencia de xantomas tendinosos, cataratas juveniles, arterioesclerosis y diarrea crónica. Las alteraciones aparecen en las primeras dos décadas de la vida, pero el diagnóstico definitivo suele hacerse tardíamente (entre la tercera y la cuarta décadas). La terapéutica consiste en la administración de ácido quenodesoxicólico asociado a pravastatina o simvastatina. El tratamiento temprano y prolongado podría detener la progresión de la enfermedad. Se presenta un paciente de 40 años con esta enfermedad y se hace una descripción actualizada de la misma.