Rheumatology Advance Access originally published online on April 27, 2007
Rheumatology 2007 46(7):1212-1213; doi:10.1093/rheumatology/kem081
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Achilles tendon enlargement and unsteady gait
Department of Internal Medicine, Vall d'Hebron General Hospital, Passeig Vall d'Hebron N° 119-139. Barcelona – 08035, Spain
Correspondence to: Dr Albert Selva-O’Callghan, C/Siracusa N° 12 bis "A", Barcelona –08012, Spain E-mail: aselva{at}vhebron.net
SIR, In September 2006, a 33-year-old woman was seen in our Department with a 6-month history of unsteady gait and frequent falls after long periods of standing. She also reported recurrent pain in the Achilles tendon over the previous 10 yrs at a rate of about four to six episodes per year. The patient had been visited by various specialists who were unable to establish a diagnosis or relieve the symptoms. During this 10-year period, both Achilles tendons had been growing and measured 7 cm at our first examination (Fig. 1). An appointment was made with an orthopaedic surgeon to assess the feasibility of surgical resection of the Achilles tendon tumours.
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At our consulting room, the patient was asked about prior health problems and daily habits. In the previous 2 years she had experienced increasing visual loss secondary to bilateral cataracts that required phaquectomy, and increased intestinal rhythm (five to seven liquid faeces a day) since early childhood. When the family was interviewed, all members spontaneously related a progressive change in the patient's mood in the last 1 or 2 years.
We established a presumptive diagnosis and performed a neurologically oriented examination that showed brisk tendon reflexes of the lower limbs, bilateral Babinski signs, and sustained ankle clonus. Complementary biochemical testing was solicited, and the laboratory findings confirmed our suspicion of cerebrotendinous xanthomatosis: cholestanol results were 4–6-fold the normal blood concentration (78.4 µmol/l, normal values: 2.0–12.6 µmol/l). A battery of neuropsychological tests demonstrated mild cognitive impairment with a predominantly frontal component, as well as asymmetrical psychomotor slowing. Magnetic resonance imaging of the brain showed bilateral hyperintensity of the nucleus dentatus on T2-weighted sequences (Fig. 2). A concurrent brain SPECT demonstrated generalized cortical hypoperfusion. Treatment with chenodeoxycholic acid 750 mg/day was started.
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One of the most characteristic signs of cerebrotendinous xanthomatosis is the remarkable tendon enlargement due to fat deposition (xanthomas); the Achilles tendon is frequently affected (Fig. 1). A history of chronic diarrhoea and cataracts has been reported in previous published cases; hence, cerebrotendinous xanthomatosis should be ruled out in young patients presenting with these two clinical manifestations [1]. Frontal dementia has also been described in cerebrotendinous xanthomatosis [2], usually together with other neurological findings (pyramidal signs, seizures, mental retardation, and cerebellar ataxia).
Cerebrotendinous xanthomatosis is a rare recessive autosomal disease caused by mutations of the sterol 27-hydroxylase gene (CYP27) that lead to reduced synthesis of bile acids, particularly chenodeoxycholic acid [3]. Absence of the negative feedback mechanism of cholic acid and chenodeoxycholic acid on 7
-hydroxylase, which is a rate-limiting enzyme in bile acid synthesis, increases the activity of this enzyme and results in an accumulation of cholesterol and cholestanol in various tissues, which is the cause of the clinical manifestations. Long-term treatment with chenodeoxycholic acid, which influences the negative feedback of cholesterol and acid bile synthesis and decreases serum cholestanol levels, can arrest or even reverse progression of the disease.
We stress the value of early diagnosis to halt the progressive neurological deterioration associated with this condition. Rheumatologists should be conscious of the existence of cerebrotendinous xanthomatosis. Clinical recognition is not difficult if one is aware of this rare disease.
The authors have declared no conflicts of interest.
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 Top References |
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- Moghadasian MH, Salen G, Frohlich JJ, Scudamore CH. Cerebrotendinous xanthomatosis: a rare disease with diverse manifestations. Arch Neurol (2002) 59:527–9.
[Abstract/Free Full Text] - Guyant-Marechal L, Verrips A, Girard C, et al. Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype. Am J Med Genet A (2005) 139:114–7.[Medline]
- Gallus GN, Dotti MT, Federico A. Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene. Neurol Sci (2006) 27:143–9.[CrossRef][Web of Science][Medline]
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