Clinical relevance of heterozygosis for aceruloplasminemia

Aceruloplasminemia is a rare form of brain iron overload of autosomal recessive inheritance that results from mutations in the CP gene, encoding the iron oxidase ceruloplasmin. Homozygous aceruloplasminemia causes progressive neurodegenerative disease, anemia, and diabetes, and is usually diagnosed...

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Bibliographic Details
Published in:American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2019-06, Vol.180 (4), p.266-271
Main Authors: Borges, Marina Dorigatti, Albuquerque, Dulcineia Martins, Lanaro, Carolina, Costa, Fernando Ferreira, Fertrin, Kleber Yotsumoto
Format: Article
Language:English
Subjects:
Adult
Anemia
Autosomal recessive inheritance
Ceruloplasmin
Ceruloplasmin - deficiency
Ceruloplasmin - genetics
CP gene
Diabetes mellitus
Female
Ferritin
Genetic counseling
genetic mutation
Genetics
Genotypes
Genotyping
Heredity
Heterozygote
Heterozygotes
Humans
Iron
Iron Metabolism Disorders - genetics
Iron Metabolism Disorders - pathology
Male
Movement disorders
Mutation
Mutation - genetics
neurodegeneration
Neurodegenerative diseases
Neurodegenerative Diseases - genetics
Neurodegenerative Diseases - pathology
Peripheral blood
Young Adult
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Summary:Aceruloplasminemia is a rare form of brain iron overload of autosomal recessive inheritance that results from mutations in the CP gene, encoding the iron oxidase ceruloplasmin. Homozygous aceruloplasminemia causes progressive neurodegenerative disease, anemia, and diabetes, and is usually diagnosed late in life upon investigation of anemia, high ferritin, or movement disorders, but its heterozygous state is less characterized and believed to be silent. Here we report two heterozygotes for new mutations causing aceruloplasminemia from whom peripheral blood samples were collected for complete blood counts, iron studies, and genotyping by automated sequencing. We then performed a systematic review of preview reports of heterozygotes with data on genotype and clinical findings. Heterozygosity for aceruloplasminemia invariably causes reduced ceruloplasmin levels, and similarly to previews reports in the literature, our cases did not present with anemia. Mild hyperferritinemia was found only in two reports. Nevertheless, 5 out of 11 variants have been associated with significant neurological symptoms despite the presence of one wild‐type alelle. This review contributes to better genetic counseling of heterozygotes for CP gene variants and supports that measuring ceruloplasmin levels may be useful when investigating patients with movement disorders or rare cases of unexplained high ferritin.
ISSN:1552-4841
1552-485X
DOI:10.1002/ajmg.b.32723