OVERVIEW

What is aceruloplasminemia?

Aceruloplasminemia, also known as hereditary ceruloplasmin deficiency, was first described by Miyajima et al. in 1987. It is an autosomal recessive disorder caused by mutations in the ceruloplasmin (CP) gene.

Its characteristics include iron-deficient erythropoiesis and tissue iron overload. Clinical symptoms mainly involve extrapyramidal signs, dementia, insulin-dependent diabetes, visual impairment, retinal degeneration, and hypochromic anemia. The absence of serum ceruloplasmin and iron deposition in the liver and basal ganglia are its hallmark features.

Is aceruloplasminemia common?

Aceruloplasminemia is a rare neurogenetic disorder, with an estimated prevalence of approximately 1 in 2 million.

Is aceruloplasminemia the same as Wilson's disease?

Aceruloplasminemia and Wilson's disease are two distinct disorders.

Aceruloplasminemia is an autosomal recessive disorder caused by mutations in the ceruloplasmin gene, with clinical manifestations including extrapyramidal signs, dementia, insulin-dependent diabetes, visual impairment, retinal degeneration, and hypochromic anemia.

Wilson's disease (WD), also known as hepatolenticular degeneration, is a hereditary copper metabolism disorder leading to liver cirrhosis and degenerative brain changes primarily in the basal ganglia. Clinical symptoms include progressive extrapyramidal signs, liver cirrhosis, Kayser-Fleischer rings (K-F rings), psychiatric symptoms, and renal impairment.

SYMPTOMS

What are the common manifestations of ceruloplasmin deficiency?

Ceruloplasmin deficiency primarily presents with three classic symptoms: diabetes, retinal degeneration, and neurological disorders. Other abnormalities such as anemia and liver dysfunction may also occur. Specific manifestations include:

• Diabetes: Blood sugar abnormalities are often detected in young or middle-aged individuals, with typical diabetic symptoms (usually non-obese diabetes). Oral hypoglycemic drugs may be ineffective, requiring insulin therapy.

• Neurological disorders:

  • Movement disorders: Eyelid spasms, grimacing, facial and cervical dystonia, tremors, chorea;
  • Ataxia: Limb ataxia, gait ataxia (unsteady and uncoordinated walking), dysarthria, nystagmus;
  • Parkinsonism: Stiffness, akinesia, etc.;
  • Patients may also experience cognitive dysfunction such as apathy and forgetfulness, or even psychiatric symptoms like hallucinations and delusions, which can progress to dementia, impairing daily living and work capacity.

• Retinal degeneration: Characteristic and distinct from diabetic retinopathy. Early macular degeneration may be detected, but vision may remain unaffected or deteriorate later.

• Anemia: Typically iron-deficient microcytic anemia, often refractory to iron supplementation. Anemia may appear before age 20, manifesting as fatigue, dizziness, palpitations, shortness of breath, pallor, and tachycardia. Children may exhibit growth retardation, intellectual disability, stomatitis, dry and brittle hair, dull and fragile nails, etc. Severe anemia may lead to shock.

• Others: Abnormal liver function, heart failure, hypothyroidism, etc.

Which parts of the body are commonly affected by ceruloplasmin deficiency?

Ceruloplasmin deficiency often affects the nervous system, blood, pancreas, liver, and retina.

How does ceruloplasmin deficiency progress?

The onset of ceruloplasmin deficiency is insidious, with slow progression. Anemia often appears before age 20, possibly accompanied by developmental delay and cognitive decline. With age, liver dysfunction, retinal degeneration, neurological symptoms, and diabetes gradually emerge. As the disease advances, memory decline and loss of self-care ability may occur.

What complications can ceruloplasmin deficiency cause?

Complications include anemic heart disease, developmental delay, intellectual disability, diabetic complications (e.g., diabetic foot, diabetic peripheral neuropathy, diabetic retinopathy), liver dysfunction, liver failure, and neurological disorders leading to ataxia or movement disorders (increasing fall risks). Memory decline and dementia may eventually result in loss of independence.

CAUSES

What causes ceruloplasmin deficiency?

Ceruloplasmin deficiency is an autosomal recessive genetic disorder. Mutations in the ceruloplasmin (CP) gene lead to copper deficiency, which disrupts cellular iron transport, causing iron accumulation in the brain and other organs such as the liver, pancreas, and retina. This results in anemia, diabetes, retinal degeneration, and neurological disorders.

Is ceruloplasmin deficiency contagious?

Ceruloplasmin deficiency is a genetic disorder and is not contagious.

How is ceruloplasmin deficiency inherited?

Ceruloplasmin deficiency is a genetic disease, often with a family history. The parents of affected individuals each carry the disease-causing gene (though they may not show symptoms). During conception, both parents pass the defective gene to the child, leading to the disease. Siblings of the patient may also be affected, with equal likelihood in males and females.

DIAGNOSIS

How is ceruloplasmin deficiency diagnosed?

Diagnosis is based on typical clinical manifestations including iron deficiency anemia, diabetes, retinal degeneration, and neurological disorders, combined with family history, low plasma ceruloplasmin levels, and characteristic MRI findings. Liver biopsy or genetic testing may be performed if necessary.

What tests are needed for ceruloplasmin deficiency?

Common tests include blood tests (complete blood count, liver function, blood glucose, ceruloplasmin, ferritin, serum iron, serum copper, urinary copper, thyroid function), MRI of the head, liver ultrasound, cardiac ultrasound, thyroid ultrasound, fundus examination, and, if necessary, liver biopsy and genetic testing.

• Complete blood count (CBC): Assesses anemia, its type, and severity. Bone marrow biopsy may be performed to determine the cause of anemia and rule out other conditions.

• Liver function tests: Evaluates liver damage. Additional tests like liver ultrasound, CT, or hepatitis screening may be done to identify the cause of liver injury.

• Blood glucose tests: Includes fasting blood glucose, postprandial blood glucose, glucose tolerance test, glycated hemoglobin (HbA1c), and insulin levels to assess diabetes and pancreatic function.

• Ceruloplasmin, ferritin, serum iron, serum copper, urinary copper: Evaluates abnormalities in copper and iron metabolism.

• Head MRI: Identifies central nervous system damage and differentiates the cause of neurological symptoms.

• Fundus examination: Checks for retinal degeneration or other ocular abnormalities.

• Cardiac ultrasound, thyroid function tests, thyroid ultrasound: Assesses heart and thyroid function.

• Liver biopsy: Confirms liver damage and detects excessive iron deposition for definitive diagnosis.

• Genetic testing: Performed if clinical symptoms, family history, and other tests are inconclusive.

What should patients with ceruloplasmin deficiency pay attention to during these tests?

• Blood tests and liver ultrasound usually require fasting for at least 8 hours. Postprandial glucose and pancreatic function tests should be conducted as directed by the doctor.

• MRI scans can be noisy; earplugs may be helpful. The procedure is time-consuming, so patients should be prepared to cooperate.

Is liver biopsy or genetic testing mandatory for ceruloplasmin deficiency?

Liver biopsy is one diagnostic method and is generally low-risk. Doctors will recommend it based on clinical necessity.

Genetic testing confirms the disease at the genetic level, especially when other tests are inconclusive. It can also screen family members and assist in prenatal diagnosis. A negative result does not rule out the diagnosis.

What diseases can ceruloplasmin deficiency be confused with?

Patients with extrapyramidal symptoms may be misdiagnosed with Parkinson's disease or chorea. Memory decline may resemble Alzheimer's disease, vascular dementia, or Parkinson's dementia.

Anemia must be differentiated from other causes.

The most critical differential diagnosis is Wilson's disease, as both conditions involve liver damage, extrapyramidal symptoms, and psychiatric manifestations. Clinical evaluation and laboratory tests help distinguish them, with genetic testing as a final option.

TREATMENT

Which department should I visit for ceruloplasmin deficiency?

It is recommended to consult the neurology department.

Can ceruloplasmin deficiency resolve on its own?

No, systematic treatment is required.

How should ceruloplasmin deficiency be treated?

The treatment for ceruloplasmin deficiency primarily involves medication:

• Iron chelators such as deferoxamine, deferiprone, deferasirox, and zinc therapy:

  • Deferoxamine: For symptomatic patients with a blood hemoglobin concentration above 9 g/dL, deferoxamine treatment may be considered. It can reduce serum ferritin levels and iron content in the brain and liver, as well as prevent the progression of neurological signs/symptoms.

  • Deferiprone: Can prevent retinal and neurodegenerative degeneration.

  • Deferasirox: May be used for patients unresponsive to deferoxamine or fresh frozen plasma therapy. It can slightly improve cognitive function, gait, and balance, and prevent tissue damage, particularly in the liver and pancreas.

  • Others: Antioxidants such as vitamin E may be used alongside chelators or oral zinc to prevent tissue damage.

• Fresh frozen plasma: Intravenous infusion can reduce iron levels in the liver, and restorative therapy may improve neurological signs/symptoms.

• Standard treatment for diabetes and anemia is required. Blood transfusions are generally unnecessary, and there is no effective treatment for retinal degeneration.

• Neurological disease treatment: Under medical supervision, symptoms such as movement disorders, Parkinsonism, ataxia, cognitive impairment, and dementia should be addressed.

Does ceruloplasmin deficiency require hospitalization?

Hospitalization is usually unnecessary. However, initial iron chelator therapy requires inpatient monitoring. Severe anemia, poorly controlled diabetes, complications, or severe neurological conditions may necessitate hospitalization.

What are the side effects of iron chelator therapy?

Side effects of iron chelators include:

• Headache, blurred vision, hives, leg muscle tremors, diarrhea, and abdominal discomfort.
• Occasional hypotension, palpitations, seizures, or shock.
• Injection site pain.
• Possible bone changes and growth retardation.
• May trigger or worsen latent pyelonephritis and increase intestinal infections.
• Overdose may lead to tachycardia, hypotension, gastrointestinal symptoms, transient vision loss, aphasia, anxiety, headache, nausea, bradycardia, or acute kidney failure. Treatment should be discontinued immediately.
• Use with caution during pregnancy and breastfeeding.

Can ceruloplasmin deficiency be completely cured?

No.

DIET & LIFESTYLE

What should patients with ceruloplasmin deficiency pay attention to in their diet?

• For those with diabetes, follow dietary guidelines under the supervision of an endocrinologist and carry sugar cubes to prevent hypoglycemia.
• Increase intake of fruits and vegetables.
• Maintain a balanced diet with both meat and vegetables. Vegetarians should consume soy products to supplement protein. If tolerable, drink 300 mL of milk daily to avoid calcium deficiency.
• Avoid relying solely on refined grains; replace part of the staple food with legumes, potatoes, pumpkins, etc.
• Use less salt and high-sodium seasonings when cooking.
• Limit consumption of pickled vegetables and meats.
• Avoid alcohol as much as possible.

What should patients with ceruloplasmin deficiency pay attention to in daily life?

Engage in moderate exercise, combining aerobic and strength training without overexertion. Ensure sufficient sleep daily. Learn self-regulation techniques when experiencing high stress or emotional tension.

Does ceruloplasmin deficiency require follow-up tests? How?

Regular follow-ups are necessary, including blood tests (e.g., complete blood count, liver function, blood glucose, ceruloplasmin, ferritin, serum iron, serum copper, thyroid function), imaging (e.g., liver ultrasound, cardiac ultrasound, thyroid ultrasound, fundus examination), and periodic neurological evaluations by a specialist.

Does ceruloplasmin deficiency affect fertility?

Severe anemia, poorly controlled blood sugar, hypothyroidism, or heart failure may impact fertility. As this is a genetic disorder, patients should seek genetic counseling before pregnancy and undergo prenatal diagnosis if already pregnant.

Can patients with ceruloplasmin deficiency fly, engage in intense exercise, or travel to high-altitude areas?

Patients with uncontrolled neurological symptoms should avoid flying, intense exercise, or high-altitude travel. Those with cardiac insufficiency or heart failure must refrain from strenuous activities and flying to prevent acute heart failure. Diabetic patients should monitor energy intake during exercise to prevent hypoglycemia.

PREVENTION

Can ceruloplasmin deficiency be prevented? How to prevent it?

Ceruloplasmin deficiency is a genetic disorder and cannot be prevented. However, patients should seek genetic counseling before pregnancy, and prenatal diagnosis is necessary if already pregnant.

How can patients with ceruloplasmin deficiency prevent complications?

• Patients may experience falls due to unsteady walking or dizziness, so fall prevention measures should be taken.

• Diabetic patients may develop complications such as hypoglycemia, hyperglycemia, or diabetic foot. They should control their diet, adhere to regular hypoglycemic medication, monitor blood sugar levels, and visit an endocrinology specialist regularly.

• Patients with heart failure should rest, avoid overexertion, and refrain from intense exercise, as it may trigger heart failure.