Case 1:
A 64-year-old woman was referred to our movement disorder clinic with
four years history of bradykinesia and rigidity. She was born as a first
child of consanguineous parents and has history of diabetes mellitus,
myelodysplastic syndrome, and gout for 15 years.
On examination, she had generalized bradykinesia and rigidity without
tremor, slow saccadic eye movements, limbs dysmetria and ataxic gait.
Other neurological examination including, cognitive, sensory, and motor
function were unremarkable.
On follow-up, after 2 years, she became wheelchair-bound due to severe
gait freezing, cognitively declined (MOCA: 19), and tremor was added to
her clinical manifestations. In addition, at that time she had severe
aggression, agitation, and visual hallucination.
The evaluation showed microcytic anemia, low serum ceruloplasmin, copper
and transferrin saturation, and increased ferritin. (Table 1) Brain MRI
detected abnormal signal intensity of the cerebellum, basal ganglia, and
midbrain. (Figure A, B) According to imaging findings and other
laboratory assessments, the diagnosis of aceruloplasminemia was
suspected. Genetic analysis was requested. The direct DNA Sequencing
revealed homozygote pathogenic variant defined as
(c.2425+1G>C) in splice region of exon 13 of CP gene. DNA
was extracted from the patient sample using salting-out technique. PCR
was used to intensify the indicated exons plus extra flanking intronic
or other non-coding sequences. Subsequently cleaning of the PCR
supplies, cycle sequencing was carried out using the ABI Big Dye
Terminator v.3.0 kit. Products were resolved by electrophoresis on an
ABI 3130 capillary sequencer. Sequencing was accomplished separately in
both the forward and reverse directions.