Clinical Guidance

No clear genotype-phenotype correlation exists for aceruloplasminemia.

Source: GeneReviews — "Aceruloplasminemia"

Diagnostic Criteria

Aceruloplasminemia is characterized by iron accumulation in the brain and viscera.

Suggestive Findings

Aceruloplasminemia should be suspected in individuals with characteristic MRI findings, more than one of the following clinical findings, and typical results on laboratory testing. MRI. Abnormal low intensities in the liver as well as the striatum, thalamus, and dentate nucleus of the brain on T1- and T2-weighted images are consistent with iron deposition and support a diagnosis of aceruloplasminemia .

Clinical findings

Source: GeneReviews — "Aceruloplasminemia"

Differential Diagnosis

Table 4.

Disorders to Consider in the Differential Diagnosis of Aceruloplasminemia

Disorder | Gene(s) | MOI | Clinical Features

Overlapping | Distinguishing (in aceruloplasminemia)

Other types of slowly progressive

NBIA with later onset1

Atypical pantothenate kinase-associated neurodegeneration (PKAN) | PANK2 | AR | Radiographic evidence of focal iron accumulation in brain, usually basal ganglia | • Iron accumulation in several visceral organs as well as brain

• Development of diabetes retinopathy

Neuroferritinopathy

| FTL | AD

Copper metabolic disorder

Wilson disease2,3 | ATP7B | AR | Ceruloplasmin deficiency | • Radiographic evidence of iron accumulation in basal ganglia, especially thalamus

• Iron accumulation in several visceral organs as well as brain

Iron metabolic disorder

Source: GeneReviews — "Aceruloplasminemia"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with aceruloplasminemia, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Iron deposition. Serum ferritin concentration; brain and abdomen MRI findings

• Neurologic findings. Brain MRI

• Diabetes mellitus. Glucose tolerance test; blood concentrations of insulin and HbA1c

• Retinal degeneration. Examination of the optic fundi and fluorescein angiography

• Anemia. Complete blood count

• Other. Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Note: Individual case reports indicate the effectiveness of treatment in individuals with aceruloplasminemia; however, no large series of symptomatic persons treated with iron chelators and zinc is available and there is no universally accepted treatment regimen. A systematic review/analysis of studies designed to evaluate the clinical effectiveness of desferrioxamine, deferiprone, deferasirox, and zinc as monotherapy for the initial treatment of various clinical presentations of aceruloplasminemia is needed. Desferrioxamine. Treatment with iron chelating agents (i.e., desferrioxamine) can be considered for symptomatic individuals whose blood hemoglobin concentration is higher than 9 g/dL.

Source: GeneReviews — "Aceruloplasminemia"

Clinical Guidance

Iron supplements. Individuals with aceruloplasminemia erroneously diagnosed as having iron deficiency anemia and treated with iron supplements had accelerated iron accumulation.

Source: GeneReviews — "Aceruloplasminemia"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Aceruloplasminemia"

Surveillance Guidelines

Marked accumulation of iron in parenchymal tissues including the liver, pancreas, heart, and thyroid can result in diabetes mellitus, cardiac failure, and hypothyroidism.

• All affected individuals should have an annual glucose tolerance test starting at age 15 years to evaluate for the onset of diabetes mellitus.

• Cardiac evaluation should be performed early in the course of the disease and repeated every year.

• Evaluation of thyroid and liver function and complete blood count are indicated annually starting at the time of diagnosis.

Source: GeneReviews — "Aceruloplasminemia"