McLeod syndrome

McLeod neuroacanthocytosis syndrome, or McLeod syndrome is an exceptionally rare disorder of the central nervous system that strikes males almost exclusively. As of 2016, only 150 cases have been described worldwide. Though its symptoms resemble other neurological disorders such as Huntington's disease, it resembles hemophilia in that it is passed from a mother who is a carrier of a faulty gene to her son.

Definition & Facts

McLeod neuroacanthocytosis syndrome is characterized by the appearance of star-shaped red blood cells called acanthocytes. Most people have a few of these types of blood cells, but high levels of them are indication of McLeod neuroacanthocytosis syndrome or a similar disease. The syndrome was named after Hugh McLeod, a dental student whose blood showed signs of the disorder.

Symptoms & Complaints

The muscles in the face and neck contract to produce grimaces, odd sounds and difficulty swallowing (dysphagia). The patient may also have seizures. About 50 percent of McLeod neuroacanthocytosis syndrome patients have cognitive impairments that make it hard for them to learn and remember.

They may also have mental disorders such as depression, obsessive-compulsive disorder, psychosis, and bipolar disorer. Their impulse control may be diminished. The patient may become apathetic, irritable, and unable to focus on one task. Some patients lose the ability to take care of themselves.

Muscle weakness and muscle atrophy are also symptoms of McLeod syndrome, as are potentially fatal conditions such as cardiac arrhythmias. The heart may be both enlarged (cardiomegaly) and weakened. Many McLeod neuroacanthocytosis syndrome patients have hemolysis without anemia, which means that their red blood cells are destroyed even though the body compensates to keep them from becoming anemic.

The onset begins in adulthood and is progressive. The usual age of onset is between 18 and 61, and most patients start to show symptoms before they turn 40. The time between the appearance of symptoms and death ranges from 7 to 51 years, and the mean age of death is 53. This premature death is often caused by seizures or heart problems.

Causes

McLeod neuroacanthocytosis syndrome is caused by a genetic mutation on the XK gene on the X chromosome. The XK gene carries the XK protein, which in turn expresses a red blood cell antigen called Kx. Scientists do not know what the function of the XK protein is. They do know that a mutated XK gene interferes with the production of the XK protein, which leads to the absence or reduction of the Kx antigen. This antigen is found in the nerve cells of the brain, heart, and muscles and determines a person’s blood type.

Boys inherit the disease from their mothers. Fathers cannot pass McLeod neuroacanthocytosis syndrome to their sons, but they can pass on the damaged gene to their daughters. These daughters will be carriers, though McLeod syndrome symptoms are exceedingly rare in females. Daughters who are carriers have a 50 percent chance of having a child who is unaffected by the mutated gene, a 25 percent chance of having a daughter who is a carrier and a 25 percent chance of having a son who has the disease. XK is the only gene known to cause McLeod neuroacanthocytosis syndrome.

Diagnosis & Tests

Diagnosis of McLeod neuroacanthocytosis syndrome is made through:

• Physical examination
• Immunohematologic tests. These tests detect antigens in the blood cells.
• Flow cytometry measures the properties of individual cells as they’re suspended in a streaming fluid.
• Tests for muscle enzymes, including elevated levels of creatine phosphokinase.
• Electroneuromyography. This checks changes in the nerves in the muscles by stimulating them with an electric current.
• Muscle computed tomography (CT) scan and biopsy
• Nerve biopsy
• Echocardiography. This is a sonogram which uses Doppler ultrasound to make two-dimensional or three-dimensional images of the heart.
• Electrocardiogram. This shows the heart’s electrical activity. It can find arrhythmias and atrial fibrillation, a dangerous condition where the heart beats erratically.
• CT scans and other imaging tests of the brain
• Molecular genetic tests

Treatment & Therapy

McLeod neuroacanthocytosis syndrome patients are given dopamine antagonists such as clozapine and haloperidol and quetiapine to ease their chorea, or jerky movements of their arms and legs. Their seizures are treated with epileptic drugs such as clobazam, levetiracetam, and phenytoin. These anti-seizure drugs also alleviate psychiatric symptoms, though some anti-seizure drugs such as lamotrigine can make seizures worse and should not be prescribed or taken.

Some patients are helped by Botox injections. Botox is a toxin that paralyzes muscles by interfering with the neurotransmitters that send signals to the nerves that control them. This eases the patient’s muscle spasms. The drug begins to work between five and 10 days after an injection, and the patient may need another course of injections when their muscle spasms return. This can be about three to four months after the initial treatment.

McLeod syndrome patients who have spasms in their throat that makes it hard for them to swallow may have difficulty eating. In some cases, they may need a feeding tube.

Surgeons also treat McLeod neuroacanthocytosis syndrome patients with deep brain stimulation. In this treatment, an electrode is inserted into an area of the brain that controls motor functions. The electrode is connected to a battery pack placed under the skin near the patient’s clavicle that sends electrical signals to the brain. This interrupts nerve signals that cause his uncontrolled movements.

Patients are helped by psychiatric treatment such as psychotherapy for themselves and counseling for themselves and their families. Teams of health professionals may be needed to provide treatment for patients and care for their families.

Prevention & Prophylaxis

To monitor his heart, the patient can wear a Holter ECG and have echocardiography every two or three years, whether he has symptoms of heart disease or not. Genetic counseling is also available.