Objective: To describe two familiar cases of hypoceruloplasminemia presenting with movement disorders

Background: Aceruloplasminemia is a metabolic disorder caused by mutations in the ceruloplasmin (CP) gene, associated with neurological and systemic features and biochemical abnormalities, including low to absent ceruloplasmin and high ferritin blood levels.

Although aceruloplasminemia is a recessive disorder, neurological disorders and milder biochemical alterations have been reported in a few subjects carrying a single variant on CP. This condition has also been called “hypoceruloplasminemia”.

Method: The proband, a 14-year-old girl, presented at 10 with subacute onset of gait ataxia and upper limbs dystonic posturing. Her parents were healthy, but an asymmetrical resting and postural hand tremor affected the mother’s brother.

Over the years, the girl experienced progressive neurological deterioration with head titubation, worsening of gait ataxia, axial jerky movements, and behavioural disorders.

Serial brain MRI examinations disclosed cerebellar atrophy. Biochemical and metabolic work-up showed a mild decrease of ceruloplasmin as the only alteration.

Results: NGS panel for movement disorder revealed a single c.2684G>C (p.G895A) variant in the CP gene that was also present in her healthy mother and her affected uncle. This variant was already reported in a patient with ataxia and dystonia associated with hypoceruloplasminemia. Low levels of blood ceruloplasmin were further confirmed and detected in the mother’s symptomatic brother. WES failed to find any other abnormalities. Based on previous observations, zinc administration was started with stabilization of clinical phenotype.

Conclusion: Hypoceruloplasminemia is controversial, as many heterozygotes for CP variants are asymptomatic. However, nearly 30 cases have been reported so far, with many of them presenting with movement disorders, such as ataxia, dystonia, myoclonus, and tremor. The pathogenesis of this phenotype is unknown. On the clinical ground, hypoceruloplasminemia is a diagnostic biomarker shared with Wilson disease. A timely diagnosis is required for both these conditions because they are potentially treatable diseases.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/progressive-myoclonus-ataxia-and-resting-tremor-in-hypoceruloplasminemia/