Diagnosing aceruloplasminemia: navigating through red herrings
Zeni Kharel1, Himal Kharel2, Pradyumna D Phatak3
1Division of Hematology/Oncology, Department of Medicine, Rochester General Hospital, Rochester, NY, USA. zeni.kharel@rochesterregional.org.
Annals of Hematology
|April 18, 2024
Summary
Aceruloplasminemia, a rare iron overload disorder, presents with hyperferritinemia, anemia, and neurological decline. Early biochemical and neuroimaging clues can aid diagnosis, differentiating it from other iron storage diseases.
Area of Science:
- Neurobiology
- Genetics
- Metabolic Disorders
Background:
- Inherited iron overload disorders are a heterogeneous group of conditions characterized by excessive iron accumulation in various organs.
- Aceruloplasminemia is a rare autosomal recessive disorder caused by mutations in the CP gene, leading to iron dysregulation and neurodegeneration.
Observation:
- A 58-year-old female presented with hyperferritinemia, normocytic anemia, and hepatic iron deposition, initially suspected as a different iron overload condition.
- Progressive neurocognitive decline and brain MRI findings suggestive of metabolic deposition disease prompted further investigation.
- Severely low serum copper and ceruloplasmin levels were identified, leading to the consideration and eventual diagnosis of aceruloplasminemia.
Findings:
- The patient exhibited a biochemical triad of hyperferritinemia, low-normal transferrin saturation, and microcytic anemia, which are key indicators for suspecting aceruloplasminemia.
- Liver biopsy revealed significant hepatic iron deposition, predominantly in hepatocytes, which is atypical for ferroportin disease.
- Neuroimaging revealed characteristic iron deposition in the basal ganglia, midbrain, and cerebellum, supporting a neurodegenerative process linked to iron dysmetabolism.
Implications:
- Aceruloplasminemia should be considered in the differential diagnosis of unexplained iron overload, especially when accompanied by neurological symptoms.
- The combination of anemia, hyperferritinemia, and neurological manifestations necessitates a thorough investigation beyond typical iron overload syndromes.
- Early diagnosis of aceruloplasminemia is crucial for initiating appropriate management and potentially slowing disease progression, although treatment options remain limited.
