AN INTERESTING CAUSE FOR ATAXIA ID NO: 1194

33 year old male patient, 1 st child of non consanguinous marriage c/o progressive unsteadiness while walking and frequent falls – from 10years of age H/o slurring of speech. H/o swelling over both ankle. No H/o seizure/sensory disturbance. No similar illness in the family.

Clinical examination: -Cerebellar signs +, -B/L immature cataract, -swelling over both achilles tendon, -Generalised wasting of muscles. MMSE: 19/30 Biochemical parameters: LIPID PROFILE: T.Cholesterol TGL HDL COMPLETE HEMOGRAM AND LFT: NORMAL ECHO AND TFT: NORMAL

Thickening and smooth symmetric hypoechoic infiltrationin achilles tendon USG

Enlarged Achilles tendon Hypointense with few linear hyperintensities

CT BRAIN Bilateral Symmetrical Hypodensities in Cerebral peduncle, medial thalamus, cerebellar white matter and dentate nucleus

MRI BRAIN

Bilateral symmetric T2, FLAIR Hyperintensities in thalamus, cerebral peduncle, periventricular white matter, cerebellar white matter and dentate nucleus

High ADC values and few foci of blooming in gradient

COMPANION CASE 36 year old man Complaints of Unsteadiness of gait Slurring of speech Cognitive decline Weakness of all four limbs

COMPANION CASE

T2, FLAIR Hyperintensities in B/L cerebellar white matter with a foci of hypointensity with it.

Foci of hypointensity in B/L Dentate nucleus representing calcification

Xanthoma in Achilles tendon and in Triceps

DIAGNOSIS CEREBRO TENDINOUS XANTHOMATOSIS (CTX)

DISCUSSION The incidence of CTX is estimated to be 3 to 5 per 100,000 people worldwide. Rare autosomal recessive condition caused by a deficiency of the mitochondrial enzyme sterol 27 hydroxylase, which normally catalyses the hydroxylation of cholestanol to bile acids. Molecular genetic analysis has revealed that this disease is associated with a mutation of the CYP 27A2 gene in chromosome 2q33. Its absence results in an accumulation of cholesterol and cholestanol in all tissues, giving rise to tendon xanthomas. These patients present with intractable diarrhea, cataracts, and psychomotor retardation (in infancy/childhood) followed by development of xanthomas after the second decade.

Achilles tendons is classically involved. Quadriceps, triceps, and finger extensor tendons may also be involved. These patients also often present with cerebellar ataxia, spasticity and peripheral neuropathy. Although blood cholesterol levels are normal in patients with CTX, the blood cholestanol levels are characteristically elevated.

IMAGING FEATURES Bilateral symmetric hyperintensity in cerebellar white matter, periventricular white matter, deep grey matter and mild cerebellar atrophy. Microcalcification in dentate nucleus. Enlarged perivascular spaces Tendon xanthoma

Achilles tendon xanthomas are classically hypointense on T1W and T2W images due to the deposition of free cholesterol and cholestanol rather than triglycerides and fatty acids (which are responsible for the normal hyperintense fat signal on T1W images). The MRI may reveal a reticular/speckled appearance due to interspersed areas of slightly high signal intensity, which are presumably due to secondary edema/inflammation.

Diagnosis is based on the typical clinical history and findings, the presence of normal or low cholesterol in association with raised cholestanol levels, and the characteristic MRI appearance. Clinically, CTX resembles the Marinesco-Sjogren syndrome, an autosomal recessive disorder characterized by the triad of cerebellar ataxia, congenital cataract, and mental retardation. The presence of tendon xanthomas helps differentiate CTX from this condition. This differentiation is important as CTX is a treatable condition. THANK YOU