A suspicion index for early diagnosis and treatment of cerebrotendinous xanthomatosis

• Published in: Journal of inherited metabolic disease 2014-05, Vol.37 (3), p.421-429
• Main Authors: Mignarri, Andrea, Gallus, Gian Nicola, Dotti, Maria Teresa, Federico, Antonio
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biochemistry; Biological and medical sciences; Child; Child, Preschool; Cholestanetriol 26-Monooxygenase - genetics; Cholestanol - blood; Early Diagnosis; Errors of metabolism; Female; Human Genetics; Humans; Infant; Internal Medicine; Lipids (lysosomal enzyme disorders, storage diseases); Male; Medical genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Original Article; Pediatrics; Xanthomatosis, Cerebrotendinous - blood; Xanthomatosis, Cerebrotendinous - complications; Xanthomatosis, Cerebrotendinous - diagnosis; Xanthomatosis, Cerebrotendinous - therapy
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-013-9674-3

Background Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder characterized by a heterogeneous presentation and a broad spectrum of clinical manifestations. Since early diagnosis and replacement therapy with chenodeoxycholic acid can prevent clinical deterioration, our aim was to develop a diagnostic tool to identify and treat CTX patients at an initial stage of the disease. Methods We devised a suspicion index, composed of weighted scores assigned to indicators such as family history characteristics and common systemic and neurological features, on the basis of a pooled analysis of selected international CTX series. The indicators were classified as very strong (score 100), strong (50) or moderate (25). The suspicion index was then applied retrospectively to our CTX population. Results Early systemic signs such as cataract, diarrhea and neonatal cholestatic jaundice were considered strong indicators, together with neurological features such as intellectual impairment, psychiatric disturbances, ataxia, spastic paraparesis and dentate nuclei abnormalities at MRI. Tendon xanthomas were regarded as very strong indicators, as was an affected sibling. A total score ≥ 100 warranted serum cholestanol assessment. Elevated cholestanol or a total score ≥ 200, with one very strong or four strong indicators, warranted CYP27A1 gene analysis. In our patients, age at diagnosis was 35.5 ± 11.8 years (mean ± standard deviation), whereas with the diagnostic tool it became 10.6 ± 9.8 years ( p