A suspicion index for early diagnosis and treatment of cerebrotendinous xanthomatosis.
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 < 0.01).


CONCLUSIONS
Our suspicion index provides a simple and inexpensive diagnostic tool allowing diagnosis and treatment of CTX before neurological disability occurs.
Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100, Siena, Italy.
Andrea
A
Mignarri
Gian Nicola
GN
Gallus
Maria Teresa
MT
Dotti
Antonio
A
Federico
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D004083:Cholestanol / Q000097:blood; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D019294:Xanthomatosis, Cerebrotendinous / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000628:therapy
D004083:Cholestanol; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase