2. Case presentation
A 31-year-old mentally retarded man was referred to our neurologic clinic with a progressive gait disorder, impaired balance, and repeated falling episodes. The patient was the third child of kinship marriage. He was delivered following a normal term pregnancy with normal birth weight and height. No history of atheromatous disease or intractable infantile-onset diarrhea was distinguished. At the age of five, he developed a blurred vision, which was diagnosed as a bilateral cataract. The patient was a school dropout due to intellectual and neuropsychiatric disability. He had developmental delays in the mental functioning and speech with a normal physical growth. At the age of 20, he developed bilateral tendinous swelling of the posterior part of the ankles that became worse over time. He complained of severe gait disturbance and ataxia since 3-4 years ago. He had frequent falling episodes resulting in multiple bone fractures. Gait disorder progressed gradually and he became non-ambulatory and wheelchair-bound. Physical examination demonstrated bilateral and symmetrical painless hypertrophy of the Achilles tendons (Fig.1). Neurological examination showed muscle weakness predominant in the distal muscles of upper and lower limbs (MRC score of 3 in the foot dorsiflexion and MRC score 2 in the finger adduction and abduction), hypertonia, brisk deep tendon reflexes, bilateral positive Babinski reflexes, and ankle clonus. The finger to nose was normal but the heel to shin was abnormal bilaterally. The laboratory results were normal for the thyroid, liver, and kidney function, serum electrolytes, and triglyceride and cholesterol level. A brain magnetic resonance imaging (MRI) discovered cerebral and cerebellar atrophy, high-intensity areas in the dentate nuclei, and symmetric hyperintensities in the cerebellar deep white matter and paraventricular white matter on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) images with corresponding hypointensities on T1-weighted (T1W) images (Fig. 2). Ultrasonography demonstrated focal areas of hypoechogenicity on the bilateral Achilles tendons measuring 3, 7, 9, 12, and 16 mm on the right and 8, 15, 11, and 14 mm on the left side. Whole exome sequencing identified a homozygous splicing mutation, NM_000784: exon3: c.465C>A; p. Tyr155* in CYP27A1gene compatible with a diagnosis of CTX. The patient was married but he was infertile. Sex hormones tests were normal. Testicular ultrasound showed that the size of the testes was in the lower limit of normal range with a normal epididymis and vein plexus. Semen analysis showed azoospermia. Analysis of the most common Y chromosome microdeletions using multiplex polymerase chain reaction and gel electrophoresis showed no microdeletions in AZFa, AZFb, and AZFc sub-regions of the long arm of chromosome Y.