Aceruloplasminemia: Causes, Symptoms, Complications, And Treatment

Aceruloplasminemia, also known as familial apoceruloplasmin or hereditary ceruloplasmin deficiency, can be described as a rare genetic disorder in which there is an abnormal accumulation of excess iron in the brain and other internal organs. Mainly, it affects neurological symptoms like cognitive impairment and movement disorders followed by retina degradation and in some cases diabetes.

Aceruloplasminemia is a genetic disorder that is inherited by the patient's autosomal recessive pattern, which means it needs to be received by one or both of the parents carrying the mutated genes. The root cause of the illness is the abnormal change in the pattern of the ceruloplasmin (CP) gene.

Autosomal recessive disease is a pattern of inheritance where the affected individual possesses two copies of the mutant gene. This disorder is only passed when both of the parents have the same genetic mutation. This can also happen if one copy of the gene is dominant and one copy is recessive.

The chances of getting affected by the genetic mutation can be different, for example, there is a 25% chance that a child may turn out to be normal with no mutation whatsoever or become get affected with two recessive genes, but in this case, there is a 50% chance that the offspring will become a carrier of the disease with no such medical condition.

The effects of the mutation show its effects in the later stages of adulthood between 20 and 60 years.

Mutation in the ceruloplasmin (CP) gene is the root cause of aceruloplasminemia. And as mentioned earlier, the inheritance of the disorder will be in an autosomal recessive pattern, which means genetic diseases have been developed by the combination of mutated genes.

Recessive genetic disorders, formed with a particular trait of chromosomes received from the mother and/or the father. When an offspring gets a non-working gene from each parent, there is the highest probability of getting affected. In other cases where an individual gets a normal working gene and a mutated non-working gene from their parents, they end up being a carrier of the disease without any specific medical condition.

Furthermore, when two individuals who are the carrier of the non-working gene consummate, the chances of passing the non-working gene with an adverse medical condition to the descendants is 25% or passing the non-working gene with no medical effects is 50% with each pregnancy.

Working genes are those which are mutated and have shown their effects on the receiver, on the other hand, non-working genes are the type of gene where there is a mutation but it does not show any adverse effect on the inherent or the receiver. In that case, the person becomes the carrier of the disease. However, in most cases, the carrier of the aceruloplasminemia may show problems coordinating movements or cerebellar ataxia in the affected individual.

CP or ceruloplasmin gene is responsible for encoding an enzyme called ceruloplasmin. Ceruloplasmin is a ferroxidase enzyme produced in the liver that is responsible for major copper-carrying protein flow in the blood along with regulating iron metabolism. Mutation in the ceruloplasmin gene decreases the level of iron in the bloodstream making it difficult for blood to transport the optimum level of iron to internal organs, which ultimately results in the accumulation of iron in the brain and other organs of the body.

Iron plays an important role in the overall functioning of the body. It helps in the function and growth of almost all the body organs. Iron accumulation damages internal organs by breaking the tissues making them fragile and causing symptoms that are associated with aceruloplasminemia.

For instance, most of the patients with aceruloplasminemia get affected in the brain, especially in the basal ganglia, which is a part of the brain that contains three clusters of brain cells known as neurons. The key role of basal ganglia is to process information associated with the coordination, movements, and cognition of the body. Iron deficiency causes an imbalance in the basal ganglia causing involuntary movements which is one of the most common signs seen in aceruloplasminemia.

Another adverse effect of iron deficiency is diabetes, which is caused when the pancreas does not get enough iron to produce the optimum level of insulin in the body to maintain a healthy blood sugar level. Also, iron deficiency in other body parts like retinas causes degradation resulting in impaired vision and other visionary abnormalities.

One of the most common effects of iron deficiency in the body is anemia, which hinders the level of oxygen flow in the body making it difficult for the body to function properly. It also causes weakness and fatigue making it difficult to conduct the daily routine activity.

Physical symptoms that are associated with aceruloplasminemia are:

• Mild anemia
• Iron deposition around retina and pancreas
• Diabetes

These physical symptoms may cause further physical complications like:

• Fatigue.
• Excessive thirst and urination.
• Weakness.
• Shortness of breath.
• Pale skin.
• Degeneration of the retinas.
• Damage to the pancreas leads to diabetes mellitus.

Basic neurological symptoms may include:

• Slurred speech or difficulty speaking (dysarthria)
• Behavioral changes
• Cognitive impairment
• Voluntary movements (ataxia)

Further psychological effects may include:

• Parkinsonism ( symptoms identical to Parkinson's disease)
• Dementia
• Emotional changes like depression

Movement disorders include:

• Chorea (rapid, involuntary, jerky movements)
• Tremors
• Dystonia (involuntary muscle contractions forcing body organs into abnormal)
• Slowness of movement
• Unable to a balanced position

The severity of symptoms may vary in each case, even amongst the ones who are sharing the same DNA ( family members). They also vary in terms of age as they can be spontaneous and occur anywhere between the 20s and 60s.

Scientists have witnessed that, Aceruloplasminemia is not the only medical condition that can possess these sets of signs and symptoms. Here are some of the following disorders that can show identical effects to those of aceruloplasminemia. These comparisons will aid your medical profession to diagnose and come up with an accurate result. maybe useful for a differential diagnosis.

• Identical to aceruloplasminemia, neurodegeneration with brain iron accumulation (NBIA) is also a rare genetic disorder that can be described as the accumulation of iron in the brain followed by a set of identical disorders like basal ganglia and neurological abnormalities. These disorders may develop during early childhood or adulthood. What makes it different from aceruloplasminemia is the presence of medical conditions like pantothenate kinase-associated neurodegeneration ( Hallervorden-Spatz disease) and infantile neuroaxonal dystrophy (Seitelberger disease) which are recessive in nature.
• Wilson’s disease is a rare genetic disorder that is identical to aceruloplasminemia as they both lead to excess copper stored in various body tissues particularly in the internal organs like the liver, brain, and corneas of the eyes. If not treated on time it may show symptoms like nervous system dysfunction and hepatic or liver disease making it identical to aceruloplasminemia. The amount of copper or iron in the body may determine the difference between the two.
• Similar to aceruloplasminemia, Iron overload disorder is the accumulation of iron in the body, especially in the liver and heart. It is a group of disorders that include hemochromatosis, neonatal hemochromatosis, astransferrinemia that does not affect the brain making it diverse from aceruloplasminemia.

Other than that a variety of neurological disorders like Parkinson's disease, Huntington's disease, dystonia, hereditary ataxias, multiple system atrophy, and dentatorubral-pallidoluysian atrophy, etc. can show identical neurological and psychological symptoms.

Diagnosis of aceruloplasminemia starts with collecting data about the patient’s and its medical history followed by a clinical evaluation and a series of tests to detect the root cause of the symptoms.

For the start, blood tests will be conducted to detect the level of iron, copper, and blood ceruloplasmin in the body.

Secondly, Magnetic resonance imaging (MRI) or the brain and other bodily parts will be conducted to see the effects of iron deficiency in organs, if the blood test and the MRI confirms the presence of most of the symptoms identical to aceruloplasminemia, a genetic test like definitive diagnostic test will be recommended to the patient to finally confirm the mutations in the CP gene.

Treatment of aceruloplasminemia is designed by medical professionals in the asymptomatic and supportive procedure. Based on results the treatment will be designed to lower or increase the level of iron in the body followed by the treatment of other illnesses like diabetes, degradation of the retina, and neurological abnormalities. Each treatment of aceruloplasminemia depends on the severity of the symptoms as they are different.

The treatment of aceruloplasminemia may include fresh frozen plasma and desferrioxamine to restore the optimum levels of ceruloplasmin. Prescribed amounts of transfusions of fresh frozen plasma will help the patient to regulate the levels of iron in the bloodstream. Even though it is not conclusively established, Iron chelators like desferrioxamine are used for treating excess iron in the body by making it dissolve in water and pass it through your kidneys via water. The patients are also recommended a strict diet to avoid any substances that can increase the level of iron in the body.

Vitamin supplements like vitamin E, have been recommended alongside medications like iron chelator or with oral zinc sulfate to repair the damage of tissue caused by aceruloplasminemia as it will protect cells from the damage of free radicals ( unstable atoms responsible for illness and aging).

Furthermore, in order to regulate the sugar level in the bloodstream insulin shots are recommended. In most cases, genetic counseling for the patient and the family is recommended.

Apart from medical treatment, your healthcare professional will recommend you a couple of dietary alterations in order to maintain the overall health of the body. In case the level of iron is high, the patient will be recommended to avoid consumables like red meat, seafood, and other food products that are high in iron or supplement iron production in the body. Also, supplements enriched in vitamin C or fortified foods must be avoided. The same will be recommended to those who have low levels of iron in the body.

Food items like grains, eggs, tea, coffee, lean protein, etc. will help the patient with high iron levels to maintain a healthy diet to smooth functioning of the body.

Summary: Aceruloplasminemia is a rare genetic disorder causing excessive levels of iron in the internal organs like the brain, pancheras, and other internal organs causing neurological impairment, retina degradation, and diabetes.