3. Discussion
Cerebrotendinous xanthomatosis is a rare autosomal recessive genetic
disorder in which cholesterol cannot be converted into bile acids due to
mutations in the CY27A1 gene that encodes the mitochondrial enzyme
sterol 27-hydroxylase 3. Half of the mutations in
CYP27A1 have been detected in exons 6–8, 16% in exon 2, and 14% in
exon 4 10,11. The mean age at onset of clinical
manifestations has been reported 19 years, but most patients are
diagnosed late (about 35 years) 12. In our case, the
patient had developmental delays in mental functioning and speech with
neuropsychiatric disorders in childhood. In terms of clinical symptoms,
patients with CTX often manifest non-neurological and neurological
symptoms such as chronic diarrhea, cataracts, tendon xanthomas, ataxia,
corticospinal tract involvement, and mental disorder. The initial
presentation of non-neurological symptoms in our patient was a cataract
that was revealed at the age of 5 years. In this patient, a CYP27A1
mutation was identified in exon 3. The characteristic brain MRI findings
are T2/FLAIR hyperintensities in the bilateral dentate nuclei, adjacent
cerebellar white matter, basal ganglia, spinal cord, and periventricular
white matter as well as cerebellar atrophy. Our patient had T2/FLAIR
hyperintensities in the bilateral dentate nuclei, white matter
alternations, and cerebellar atrophy 13–15. One of
the symptoms in our case was infertility, which was not reported in
previous studies. The cause of infertility in this patient was
non-obstructive azoospermia due to a lack of spermatogenesis in the
testicles. The sex hormones, prolactin, and testosterone levels were
normal. Co-occurrence of azoospermia in CTX patients may be due to the
accumulation of cholesterol in the scrotum sac affecting spermatogenesis
and the function of the male reproductive system. Cholesterol has been
revealed to cause a reduction in sperm kinetics and has negative effects
on Leydig and Sertoli cells secretory capacity in rabbits. Previous
studies found that changed lipid metabolism in seminal plasma plays a
role in male infertility 16–18. Accumulation of
cholesterol in tissues is one of the obvious symptoms of CTX, but the
resultant functional abnormalities are unknown. The relationship between
infertility and cholesterol should be further investigated since it has
not been addressed so far.