Hallervorden-Spatz Disease - Symptoms, Causes and Treatment

Introduction:

Hallervorden-Spatz disease, also known as pantothenate kinase-associated neurodegeneration, is an inherited neurological movement disorder associated with iron accumulation in the brain. It is characterized by progressive degeneration of specific regions in the central nervous system. The most common feature of this disease is iron accumulation in the brain in an ‘eye of the tiger sign pattern’ along with a progressive movement disorder. Another common feature is degeneration of the retina. It was first described by Dr. Julius hallervorden and Dr. Hugo Spatz in 1922. Hallervorden-Spatz disease affects males and females equally. The symptoms often develop during childhood, and occasionally begin during late adolescence or adulthood. It is a rare disorder, and the frequency is estimated to be one to three per million individuals worldwide.

What Are the Signs and Symptoms of the Hallervorden-Spatz Disease?

The sign and symptoms of this disease may vary greatly from case to case. They include:

• Dystonia (sustained muscle contractions causing repetitive movements).

• Spasticity (sudden involuntary muscle spasm).

• Dysarthria (abnormal speech).

• Muscular rigidity.

• Poor balance.

• Night blindness.

• Loss of side vision.

• Rigid muscles.

• Tremors.

• Confusion.

• Writhing movements.

• Dementia (loss of memory).

• Weakness.

• Drooling.

• Difficulty in swallowing.

• Stupor.

• Disorientation.

• Facial grimacing.

• Painful muscle spasms.

What Is the Cause of the Hallervorden-Spatz Disease?

People with the hallervorden-Spatz disease have an abnormal iron accumulation in certain brain parts. This is usually seen in regions of the basal ganglia called the globus pallidus and the substantia nigra. The basal ganglia is a collection of structures deep in the brain that helps regulate movements. The exact relation between iron accumulation and the symptoms of the hallervorden-Spatz disease is not fully understood. Hallervorden-Spatz disease is an autosomal recessive condition caused by mutations in the PANK2 (pantothenate kinase 2) gene. This gene encodes the pantothenate kinase enzyme, and mutations in the gene result in an inborn error in vitamin B5 metabolism. Vitamin B5 metabolism is necessary for the production of coenzyme A in cells. Disruption in this enzyme results in affecting energy and lipid metabolism and may cause the accumulation of potentially harmful compounds in the brain, including iron.

How to Diagnose Hallervorden-Spatz Disease?

The diagnosis of the hallervorden-Spatz disease is made by taking a detailed patient history, a thorough clinical examination, and specialized tests. The recommended tests include:

• Blood Test - The levels of copper, lipids, amino acids, ceruloplasmin, and acanthocytes are measured in the blood to rule out other conditions.

• Radionuclide Scan - This test reveals increased iron uptake in the basal ganglia.

• CT (Computed Tomography) Scan - This test may show hypodensity in the basal ganglia and atrophy of the brain. Calcification in the basal ganglia without any atrophy has also been described.

• MRI (Magnetic Resonance Imaging) Scan - This test reveals the ‘eye of the tiger’ sign, a dark area indicating the accumulation of iron with a bright spot in the center.

• Molecular Genetic Testing - This test is done for the full gene sequence of the PANK2 gene. This test is the gold standard for making the diagnosis.

What Is Differential Diagnosis of Hallervorden-Spatz Disease?

• Infantile Neuroaxonal Dystrophy - It is also known as Seitelberger disease. It is a rare inherited neurological disorder characterized by axons (nerve endings) abnormalities within the brain and spinal cord and outside the central nervous system.

• Familial Idiopathic Basal Ganglia Calcification - It is a rare neurological disorder with the presence of abnormal calcium deposits of unknown cause.

• Fucosidosis - It is a rare inherited disorder characterized by the deficiency of the alpha-L-fucosidase enzyme, which is required to break down certain complex compounds.

• Wilson Disease - It Is a genetic disorder that is characterized by excess copper stored in different body parts such as the liver, brain, and cornea.

• Batten Disease - This disease belongs to a group of progressive degenerative neurometabolic disorders. It is characterized by abnormal accumulation of certain fatty, granular substances in the nerve cells of the brain and other tissues of the body that may cause progressive deterioration of certain areas of the brain, neurological impairment, and other symptoms and physical findings.

• Neuroacanthocytosis - It is a general word used for rare progressive disorders characterized by the association of spiny red blood cells, misshapen and neurological abnormalities.

• Parkinson's Disease - It is a slowly progressive neurological disorder that is characterized by muscular stiffness, involuntary trembling, slow movement, and difficulty carrying out voluntary movements.

• Huntington's Disease - It is a progressive, genetic neurodegenerative disorder characterized by the gradual development of involuntary muscle movements affecting the feet, hands, face, and trunk and progressive deterioration of memory (dementia).

What Are the Treatment Options for Hallervorden-Spatz Disease?

The treatment plan focuses on managing the specific symptoms as there is no specific treatment for the hallervorden-Spatz disease. The treatment of this disease requires coordinated efforts of a pediatrician, neurologist, ophthalmologist, geneticist, and physiatrist.

• Supportive Therapy - This may include exercise physiology, occupation therapy, physical therapy, speech pathology, and feeding or nutrition.

• Medications - Baclofen, Clonazepam, and Trihexyphenidyl are prescribed to give relief from disabling dystonia. These medicines are taken orally. In the later stage of the disease, a Baclofen pump can be used to administer regular doses into the central nervous system. Drugs that reduce the level of iron in the body are also prescribed. Anti-convulsive drugs are prescribed to relieve seizures.

• Surgery - Two surgical procedures, namely pallidotomy and thalamotomy, have been investigational attempts at controlling dystonia. These procedures destroy the specific regions of the grain, the thalamus, and the pallidum. Some patients have reported some temporary and immediate relief.

Hallervoren-Spatz disease gets worse with time as it tends to progress faster in children with the condition than in adults. However, medical advances have been shown to have increased life expectancy.

What Are the Complications of Hallervorden-Spatz Disease?

The inability to move can cause the following health problems:

• Bed sores.

• Blood clots.

• Skin breakdown.

• Infections of the respiratory system.

Conclusion:

Hallervorden-Spatz disease is a rare neurological disorder. This disorder affects the patient’s ability to move. There is no known way of preventing this disorder. Genetic counseling is often recommended for families with a history of the hallervorden-Spatz disease.