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.