Aceruloplasminemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Aceruloplasminemia is a disorder in which iron gradually accumulates in the brain and other organs. Iron accumulation in the brain results in neurological problems that generally appear in adulthood and worsen over time.

People with aceruloplasminemia develop a variety of movement problems. They may experience involuntary muscle contractions (dystonia) of the head and neck, resulting in repetitive movements and contortions. Other involuntary movements may also occur, such as rhythmic shaking (tremors), jerking movements (chorea), eyelid twitching (blepharospasm), and grimacing. Affected individuals may also have difficulty with coordination (ataxia). Some develop psychiatric problems and a decline of intellectual function (dementia) in their forties or fifties.

In addition to neurological problems, affected individuals may have diabetes mellitus caused by iron damage to cells in the pancreas that make insulin, a hormone that helps control levels of blood sugar, also called blood glucose. Iron accumulation in the pancreas reduces the cells' ability to make insulin, which impairs blood glucose regulation and leads to the signs and symptoms of diabetes.

Iron accumulation in the tissues and organs results in a corresponding shortage (deficiency) of iron in the blood, leading to a shortage of red blood cells (anemia). Anemia and diabetes usually occur by the time an affected person is in his or her twenties.

Affected individuals also have changes in the light-sensitive tissue at the back of the eye (retina) caused by excess iron. The changes result in small opaque spots and areas of tissue degeneration (atrophy) around the edges of the retina. These abnormalities usually do not affect vision but can be observed during an eye examination.

The specific features of aceruloplasminemia and their severity may vary, even within the same family.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the CP gene cause aceruloplasminemia. The CP gene provides instructions for making a protein called ceruloplasmin, which is involved in iron transport and processing. Ceruloplasmin helps move iron from the organs and tissues of the body and prepares it for incorporation into a molecule called transferrin, which transports it to red blood cells to help carry oxygen.

CP gene mutations result in the production of ceruloplasmin protein that is unstable or nonfunctional, or they prevent the protein from being released (secreted) by the cells in which it is made. When ceruloplasmin is unavailable, transport of iron out of the body's tissues is impaired. The resulting iron accumulation damages cells in those tissues, leading to neurological dysfunction, and the other health problems seen in aceruloplasminemia.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Aceruloplasminemia has been seen worldwide, but its overall prevalence is unknown. Studies in Japan have estimated that approximately 1 in 2 million adults in this population are affected.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal enzyme/coenzyme activity · Very frequent (99-80%)

Concentration or activity of an enzyme is above or below the limits of normal in the blood circulation.

Abnormality of the nervous system · Very frequent (99-80%)

An abnormality of the nervous system.

Aceruloplasminemia · Very frequent (99-80%)

Absence of ceruloplasmin in the blood.

Hypochromic microcytic anemia · Very frequent (99-80%)

A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes and lower than normal size of the erythrocytes.

Increased circulating ferritin concentration · Very frequent (99-80%)

Increased concentration of ferritin in the blood circulation.

Refractory anemia · Very frequent (99-80%)

Abnormality of retinal pigmentation · Frequent (79-30%)

Any deviation from the normal pigmentation of the retina.

Ataxia · Frequent (79-30%)

Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Other findings in the same source

From: Orphanet

Additional reported features include Chorea (Frequent (79-30%)); Cognitive impairment (Frequent (79-30%)); Decreased circulating ceruloplasmin concentration (Frequent (79-30%)); Decreased circulating copper concentration (Frequent (79-30%)); Decreased serum iron (Frequent (79-30%)); Diabetes mellitus (Frequent (79-30%)); Dysarthria (Frequent (79-30%)); Dystonia (Frequent (79-30%)); Elevated hepatic iron concentration (Frequent (79-30%)); Gait ataxia (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Aceruloplasminemia is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Aceruloplasminemia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.