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Year : 2016  |  Volume : 5  |  Issue : 3  |  Page : 218-221

Bilateral xanthomas of tendoachilles in a patient of cerebro-tendinous xanthomatosis: A case report

Department of Orthopaedics and Traumatology, Osmania Medical College, Hyderabad, Andhra Pradesh, India

Date of Web Publication10-Oct-2016

Correspondence Address:
Vutukuru Sri Ravindranath
Plot No. 50, SrinivasaNagar Colony West, S. R. Nagar, Hyderabad - 500 038, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2277-8632.191851

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Cerebro-tendinous xanthomatosis is a very rare autosomal recessive disorder. An 18-year-old male presented to us with swellings of both tendoachilles, proved to be xanthomas. The diagnosis was confirmed by biochemical, clinical, and radiological studies. Such a rare and perplexing case of tendon xanthomas in this disorder should be kept as a differential diagnosis for the more common tendon swellings of this region as the conditions are treated differently. The mere postoperative recurrence in this case clearly proves that surgical excision is not the right treatment option for cerebro-tendinous xanthomatosis, which can be the primary tempting option.

Keywords: Bilateral xanthomas, cerebro-tendinous xanthomatosis, tendo achilis

How to cite this article:
Ravindranath VS, Sastry V, Sharma V, Sravanthi V L. Bilateral xanthomas of tendoachilles in a patient of cerebro-tendinous xanthomatosis: A case report. J NTR Univ Health Sci 2016;5:218-21

How to cite this URL:
Ravindranath VS, Sastry V, Sharma V, Sravanthi V L. Bilateral xanthomas of tendoachilles in a patient of cerebro-tendinous xanthomatosis: A case report. J NTR Univ Health Sci [serial online] 2016 [cited 2022 Nov 28];5:218-21. Available from: https://www.jdrntruhs.org/text.asp?2016/5/3/218/191851

  Introduction Top

Cerebro-tendinous xanthomatosis is an autosomal recessive disorder. It can manifest at any age from neonatal stage to sixth decade. The primary defect is in mitochondrial sterol 27-hydroxylase enzyme, which results in defective bile acid synthesis from cholesterol. This ultimately leads to deposition of cholesterol and cholestenol in the central nervous system, peripheral tendons, and muscles including the heart, lungs, and blood vessels, resulting in degenerative process which continues uninterruptedly over time unless it is treated with appropriate medication. The patients suffer from chronic diarrhea and cataract in early decades of life. They also present with painful swellings of tendoachilles of both the legs in the second decade. Full-blown disorder results in cerebral symptoms initially in the form of low intelligence which then progresses to dementia, convulsions, and abnormal movements. Out of all, the central nervous symptoms are more disabling and the situation continues to worsen further as they become older, making them completely dependent. Here we describe such a classical presentation of this rare disorder that has to be considered in the differential diagnosis of commonly occurring tendon xanthomas secondary to simple hyperlipidemic disorders, for which surgical excision may be the correct option. But the present condition recurs after surgery, and appropriate medical therapy soon after early diagnosis is the only option for retarding the disease progression without considering surgery.

  Case Report Top

An 18-year-old male presented with bilateral, firm, nodular, tender, slow-growing swellings involving both the achilles tendons, found since past 4 years [Figure 1], [Figure 2] and [Figure 7]. The intensity of pain and discomfort used to increase as he continued to walk, thus limiting his walking distance. Past history indicated that he was a normally delivered child with history of cataract surgery done 10 years ago, along with history of chronic diarrhea. He did not suffer from icterus or convulsions. Family history revealed that he was a child of a consanguineous marriage. His sibling, a girl, was normal.
Figure 1: Short-statured male with bilateral swellings of the tendoachilles region

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Figure 2: Bilateral swellings of the tendoachilles region

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Figure 7: Postoperative follow-up after 2 years revealing enlargement of the operated tendon

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He had short stature, was thin built, and slow cerebrated with low IQ. However, he was coherent and cooperative. No clubbing of the fingers was seen. Peculiarly, conjunctiva was yellowish. Hematological and biochemical investigations including liver function tests, lipid profile, thyroid function tests, and ultrasound examination of abdomen were normal. A special test measuring “blood cholestenol” level found it to be elevated to 43.7 µg/ml. Radiographs showed homogenous soft tissue shadow in the area of tendoachilles in both his lower legs. MRI showed homogenous hyperintense signals with fusiform swellings of tendoachilles [Figure 3] and [Figure 4]. Surgical excision of the swollen tendon was done, followed by reconstruction using peroneus brevis tendon [Figure 5] and [Figure 6]. Biopsy of the specimen revealed it to be a xanthoma with cholesterol crystals. Based on the clinical picture, radiological and pathological confirmation, the patient was found to have cerebro-tendinous xanthomatosis. Postoperative period was uneventful. The latest follow-up after a couple of years revealed reappearance of the swelling in the reconstructed tendon.
Figure 3: Radiographs showing homogenous shadow in the area of tendoachilles, fusiform in shape in both the legs

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Figure 4: MRI showing homogenous hyperintense signals with fusiform swelling of tendoachilles

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Figure 5: Excised piece of the affected tendon during surgery

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Figure 6: Cut section of the excised piece of the affected tendon during surgery

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  Discussion Top

Cerebro-tendinous xanthomatosis is a rare genetic metabolic disorder of cholesterol and bile acid metabolism that results in systemic and neurologic abnormalities. Typically, the disease begins in infancy with chronic diarrhea. Cataracts become evident in childhood or adolescence, and xanthomata develop in the second and third decades of life. Significant neurologic impairment also occurs, such as seizures, dementia, and extrapyramidal dysfunction, which typically begins in the third decade of life and progresses until death, if left untreated. Our patient showed all the typical features of the disorder, except seizures and symptoms of extrapyramidal dysfunction.

The primary enzymatic defect in cerebro-tendinous xanthomatosis is in mitochondrial sterol 27-hydroxylase, a key enzyme in the process of bile acid synthesis from cholesterol.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] Defects in the enzyme result in decreased synthesis of chenodeoxycholic acid (CDCA), leading to bile acid precursor accumulation in tissues. Deposition of cholestanol and cholesterol in the CNS (the brain and spinal cord), muscle (including the heart), blood vessels, and tendons results in a degenerative process that worsens over time unless treated. Causes of death reported in the literature include myocardial infarction and progressive mental deterioration with pseudobulbar palsies.

Morbidity begins with intractable diarrhea. Presenile cataracts result in vision abnormalities. Xanthomas can cause motor restriction and joint deformities, resulting in ambulation disabilities. Vascular abnormalities such as premature atherosclerosis (especially in the carotid and coronary vessels) can lead to stroke and myocardial infarction. The primary neurologic manifestations of the disease are associated with complications that range from treatable seizures to neurologic devastation. The severity of disease varies widely.

Chronic, sometimes intractable diarrhea occurs, with onset typically in infancy.[17],[18],[19],[20],[21],[22],[23] The diarrhea continues through adulthood, if left untreated.[12] Neonatal or infantile hepatitis and prolonged jaundice have been described.[13]

Juvenile cataracts may be a presenting sign.[14],[15],[16] Xanthomas are rarely seen before age 20 years, although an exaggerated phenotype may be observed in patients with heterozygous familial hypercholesterolemia and cerebro-tendinous xanthomatosis.[25] They are usually found on the achilles tendon, but may also be found on the patella, elbow, hand, and neck tendons. They have also been reported on the parenchyma of the lungs and brain, as well as in the bones.

In our patient, the lipid profile with high- and low-density lipoprotein as well as the cholesterol levels was within the normal range. The cholestanol level was typically 3-15 times higher than the mean plasma levels in unaffected individuals; the normal levels range from 1.3 to 15 mg/dl.[12] In our patient, the cholestanol level was 43.7 µg/ml. The cholesterol-to-cholestanol ratio is said to be a better indicator of disease than the cholestanol concentration alone.[24]

The radiographs revealed fusiform soft tissue swellings, which were found as hyperintense signals in those regions in the MRI. Surgical excision of the tendon was done and biopsy of the excised gross specimen confirmed the mass as a xanthoma. Keeping in view the significant past history, neurologic symptoms, and elevated blood cholestenol levels, a systemic disorder like cerebro-tendinous xanthomatosis should be kept in the differential diagnosis, and surgery should have been deferred since it results in significant morbidity in an already mentally retarded and uncooperative patient usually. Also, there are other systemic disorders that can cause tendoachilles swellings, such as inflammatory, autoimmune, neurologic, and neoplastic conditions. Some of them can be treated by medical therapies; surgery must be the last option, as proved by the recurrence of the swelling in the reconstructed tendon.

  Conclusion Top

There are different causes of tendon swellings, of which a rare but treatable cause is cerebro-tendinous xanthomatosis. Early recognition of this entity is important as it can be treated using an effective medical therapy that can even reverse the disease manifestations. Surgery should not be the option for tendon xanthomata without the confirmation of the cause, as it could be a part of a systemic pathology.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

  References Top

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Salen G. Cholestanol deposition in cerebrotendinous xanthomatosis. A possible mechanism. Ann Intern Med 1971;75:843-51.  Back to cited text no. 2
Salen G, Meriwether TW, Nicolau G. Chenodeoxycholic acid inhibits increased cholesterol and cholestanol synthesis in patients with cerebrotendinous xanthomatosis. Biochem Med 1975;14:57-74.  Back to cited text no. 3
Oftebro H, Björkhem I, Skrede S, Schreiner A, Pederson JI. Cerebrotendinous xanthomatosis: A defect in mitochondrial 26-hydroxylation required for normal biosynthesis of cholic acid. J Clin Invest 1980;65:1418-30.  Back to cited text no. 4
Clayton PT, Verrips A, Sistermans E, Mann A, Mieli-Vergani G, Wevers R. Mutations in the sterol 27-hydroxylase gene (CYP27A) cause hepatitis of infancy as well as cerebrotendinous xanthomatosis. J Inherit Metab Dis 2002;25:501-13.  Back to cited text no. 5
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.  Back to cited text no. 6
Sugama S, Kimura A, Chen W, Kubota S, Seyama Y, Taira N, et al. Frontal lobe dementia with abnormal cholesterol metabolism and heterozygous mutation in sterol 27-hydroxylase gene (CYP27). J Inherit Metab Dis 2001;24:379-92.  Back to cited text no. 7
Panzenboeck U, Andersson U, Hansson M, Sattler W, Meaney S, Björkhem I. On the mechanism of cerebral accumulation of cholestanol in patients with cerebrotendinous xanthomatosis. J Lipid Res2007;48:1167-74.  Back to cited text no. 8
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von Bahr S, Bjorkhem I, Van'tHooft F, Alvelius G, Nemeth A, Sjövall J, et al. Mutation in the sterol 27-hydroxylase gene associated with fatal cholestasis in infancy. J Pediatr Gastroenterol Nutr 2005;40:481-6.  Back to cited text no. 11
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Cruysberg JR, Wevers RA, Tolboom JJ. Juvenile cataract associated with chronic diarrhea in pediatric cerebrotendinous xanthomatosis. Am J Ophthalmol 1991;112:606-7.  Back to cited text no. 13
Cruysberg JR, Wevers RA, van Engelen BG, Pinckers A, van Spreeken A, Tolboom JJ. Ocular and systemic manifestations of cerebrotendinous xanthomatosis. Am J Ophthalmol 1995;120:597-604.  Back to cited text no. 14
Dotti MT, Rufa A, Federico A. Cerebrotendinous xanthomatosis: Heterogeneity of clinical phenotype with evidence of previously undescribed ophthalmological findings. J Inherit Metab Dis 2001;24:696-706.  Back to cited text no. 15
Monson DM, DeBarber AE, Bock CJ, Anadiotis G, Merkens LS, Steiner RD, et al. Cerebrotendinous xanthomatosis: A treatable disease with juvenile cataracts as a presenting sign. Arch Ophthalmol 2011;129:1087-8.  Back to cited text no. 16
Guyant-Marechal L, Verrips A, Girard C, Wevers RA, Zijlstra F, Sistermans E, et al. Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype. Am J Med Genet A 2005;139A:114-7.  Back to cited text no. 17
Huijgen R, Stork AD, Defesche JC, Peter J, Alonso R, Cuevas A, et al. Extreme xanthomatosis in patients with both familial hypercholesterolemia and cerebrotendinous xanthomatosis. Clin Genet 2012;81:24-8.  Back to cited text no. 18
Koyama S, Kawanami T, Tanji H, Arawaka S, Wada M, Saito N, et al. A case of cerebrotendinous xanthomatosis presenting with epilepsy as an initial symptom with a novel V413D mutation in the CYP27A1 gene. Clin Neurol Neurosurg 2012;114:1021-3.  Back to cited text no. 19
Dotti MT, Manneschi L, Federico A. Mitochondrial enzyme deficiency in cerebrotendinous xanthomatosis. J Neurol Sci 1995;129:106-8.  Back to cited text no. 20
Fujiyama J, Kuriyama M, Arima S, Shibata Y, Nagata K, Takenaga S, et al. Atherogenic risk factors in cerebrotendinous xanthomatosis. Clin Chim Acta 1991;200:1-11.   Back to cited text no. 21
Berginer VM, Shany S, Alkalay D, Berginer J, Dekel S, Salen G, et al. Osteoporosis and increased bone fractures in cerebrotendinous xanthomatosis. Metabolism 1993;42:69-74.  Back to cited text no. 22
Seyama Y. Cholestanol metabolism, molecular pathology, and nutritional implications. J Med Food 2003;6:217-24.   Back to cited text no. 23
Verrips A, van Engelen BG, Wevers RA, van Geel BM, Cruysberg JR, van den Heuvel LP, et al. Presence of diarrhea and absence of tendon xanthomas in patients with cerebrotendinous xanthomatosis. Arch Neurol 2000;57:520-4.  Back to cited text no. 24
Huijgen R, Stork AD, Defesche JC, Peter J, Alonso R, Cuevas A, et al. Extreme xanthomatosis in patients with both familial hypercholesterolemia and cerebrotendinous xanthomatosis. Clin Genet 2012;81:24-8.  Back to cited text no. 25


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]


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