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Wilson's disease (WD) and hypoceruloplasminemia are both autosomal recessive disorders associated with low-serum ceruloplasmin that can cause neurological symptoms. WD is due to a defect in copper transport and WD patients with neurological symptoms typically have copper deposits in the cornea [Kayser-Fleischer (K-F) rings]. Hypoceruloplasminemia, unlike WD, leads to iron accumulation in the CNS causing neurological symptoms and signs. We report a patient with predominant ataxia, low-serum ceruloplasmin and without K-F rings initially diagnosed with hypoceruloplasminemia who was later discovered to have WD.
A 35-year-old woman presented with 6 years of gradually progressive bilateral arm tremor, slurred speech, incoordination, gait imbalance, and difficulty multi-tasking in her job. There was no family history of ataxia or similar problems in her family. Examination revealed scanning speech and no obvious cognitive impairment. She had ocular dysmetria with overshoot and jerky saccades. Motor exam revealed mild bradykinesia and slight postural and action tremor in both arms, but no cogwheel rigidity. Coordination was impaired on finger-to-nose and heel-to-shin. She had truncal titubation and was unable to perform tandem gait. Deep tendon reflexes were symmetric and plantar responses were flexor.
Serum ceruloplasmin was 4.5 mg/dL (ref.
22.9-43.1) and serum ferritin was 13.5 ng/mL (ref. 7-282). Urinary copper, complete blood count, peripheral blood smear for acanthocytes, comprehensive metabolic profile, ANA screen, Vitamin E studies, heavy metal screen, screening for inborn errors of metabolism, and anti-gliadin antibodies were unrevealing. Commercially available genetic testing for mitochondrial diseases and Friedreich's ataxia as well as complete ataxia panel for spinocerebellar ataxias was also negative. slit lamp examination by two different ophthalmologists confirmed the absence of K-F rings.
MRI of the brain revealed generalized mild atrophy with increased signal on T1 weighted images in the bilateral thalami, posterior midbrain, and pons as well as decreased signal intensity in the globus pallidus and putamen bilaterally in T2-weighted sequences (Figure 1). MRI of the abdomen revealed no abnormalities of the liver at that time.
A presumptive diagnosis of hypoceruloplasminemia was made and the patient was treated with the iron chelator desferroxamine and then switched to trientine due to intolerable