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.