What gene is mutated in metachromatic leukodystrophy?
The most common cause of metachromatic leukodystrophy is a mutation in the ARSA gene. This mutation results in a lack of the enzyme that breaks down lipids called sulfatides that build up in the myelin.
What age does metachromatic leukodystrophy appear?
The forms are based on when the symptoms begin: Late infantile MLD symptoms usually begin by ages 1 to 2. Juvenile MLD symptoms usually begin between ages 4 and 12. Adult (and late-stage juvenile MLD) symptoms may occur between age 14 and adulthood (over age 16), but may begin as late as the 40s or 50s.
How many people have metachromatic leukodystrophy?
Metachromatic leukodystrophy is reported to occur in 1 in 40,000 to 160,000 individuals worldwide.
Is metachromatic leukodystrophy fatal?
The prognosis for MLD is poor. Most children within the infantile form die by age 5. Symptoms of the juvenile form progress with death occurring 10 to 20 years following onset. Those persons affected by the adult form typically die withing 6 to 14 years following onset of symptoms.
What triggers leukodystrophy?
What causes these disorders? All leukodystrophies are the result of genetic defects (mutations). Myelin, which is whitish in color and makes up much of the white matter in the brain, is a complex substance made up of many different proteins and lipids (fatty substances).
Is there a genetic test for metachromatic leukodystrophy?
The diagnosis of MLD is made through both genetic and biochemical testing. Genetic testing can identify mutations in the ARSA and PSAP genes. Biochemical testing includes sulfatase enzyme activity and urinary sulfatide excretion.
How long do children with MLD live?
Eventually the combination of the diseased brain and physical weakness becomes too great to sustain life, and death usually occurs between the ages of five to eight years. Parents and carers will be aware of the child’s increasing frailty, and death is usually relatively peaceful and expected when the time comes.
Can leukodystrophies be misdiagnosed?
Diagnostic evaluation is usually based on Magnetic Resonance Imaging (MRI), clinical hallmarks, and different metabolic or genetic tests. Due to the rarity of these diseases, patients are often misdiagnosed as having multiple sclerosis or other neurologic diseases.
Is leukodystrophy an autoimmune disease?
Leukodystrophies may be classified as hypomyelinating or demyelinating diseases, depending on whether the damage is present before birth or occurs after. Other demyelinating diseases are usually not congenital and have a toxic or autoimmune cause.
…
| Leukodystrophy | |
|---|---|
| Specialty | Neurology |
Can metachromatic leukodystrophy be misdiagnosed?
Common misdiagnoses for MLD include Cerebral Palsy, Batten’s Disease, and ADHD – especially with children.
How do kids get MLD?
MLD is an autosomal recessive genetic disorder. Recessive genetic disorders occur when both copies of the gene are affected. If a child is affected, most of the time, their parents are carriers, meaning each parent will have one changed (mutated) copy and one normal copy of the ARSA gene, but will not have symptoms.
How common is MLD?
Often misdiagnosed as ADHD or other behavioral problems until fine or gross motor skills are affected. Adult MLD — the least common form of MLD, occuring in about 10% of patients. Typically, this form of the disease progresses more slowly.
What does MLD do to the body?
Metachromatic leukodystrophy (MLD) is a rare hereditary disease characterized by accumulation of fats called sulfatides. This causes the destruction of the protective fatty layer (myelin sheath) surrounding the nerves in both the central nervous system and the peripheral nervous system.
What are signs of MLD?
Symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. Children may become comatose. Most children with this form of MLD die by age 5.
Is MLD inherited?
MLD is inherited in a recessive fashion. That means for a person to develop the disease, both inherited genes associated with MLD must be defective. If a child inherits only one defective gene, he or she is a carrier of the disease, but is unlikely to develop MLD.
How many cases of MLD are there?
Affected Populations
The true prevalence rate of MLD is unknown, but is estimated to be between 1 in 40,000 and 1 in 160,000. The Navajo also have a higher prevalence rate of 1 in every 2,500 people. In certain populations in the Middle East, these numbers may be even higher.