Metachromatic Leukodystrophy (MLD) is a rare, genetic, degenerative neurometabolic disorder that affects one in 40,000 children worldwide.

MLD is most often caused by a gene mutation, ie. deficiency or deficiency of the enzyme in the body – arylsufatase A (ARSA). This enzyme is necessary for the breakdown and cleaning of cells from sulfatides.

There is a deposition of these fats in the white matter of the brain and they attack the CNS-central nervous system, causing the destruction of the myelin sheath around the nerves, i.e. demyelination occurs, MYELIN is destroyed. Accumulation of sulfatide occurs in the liver, kidneys and other organs.

Myelin is a protective covering of a nerve fiber made of tissue consisting of fat and proteins, and it enables fast, even and efficient transmission of nerve impulses. It is often compared to the insulation around wires, conductors. It allows current to flow through the conductor, if it is missing or badly damaged, a short circuit occurs. When some part of the myelin sheath is damaged, the transmission of impulses is disturbed, slowed down, interrupted, due to which messages from the brain reach their destination with a delay, wrongly or not at all. These changes in the myelin sheath cause various symptoms of weakness, tingling in the arms, legs, loss of acquired functions, paralysis, blindness, seizures and death.

Other symptoms are generally the same as in other leukodystrophies:

– irritability (overreaction to ordinary stimuli

sound, smell, light, heat, cold)

the term refers to children who are due to illness

nervous, scared for no apparent reason

-difficulty in feeding, difficult swallowing

-difficulties in walking, clumsiness, clumsiness

-loss of muscle control and sudden fall

-difficulty in speaking, slurred speech

– hypotonia (decreased muscle tone)

-abnormally high muscle tone

-abnormal muscle movements

-ataxia (loss of ability to coordinate muscle movement)

– quadriplegia (paralysis from the neck down)


-nystagmus (a type of abnormal eye movement)

– optic nerve atrophy

– problematic behavior

– psychomotor regression

-reduced mental functions

– inability to perform tasks normally

– a change in the sensitivity of the skin that spreads and spreads over the hands,

legs, on the body

– attacks not epileptic but attacks of muscle tension which

cause twisting of the body, head, arms and legs

There are several forms of MLD (Metachromatic Leukodystrophy).


After a period of apparently normal growth and development in a child, skills such as walking and talking can deteriorate. Affected children have difficulty walking after the first year, usually around 15-24 months of age. Symptoms include irritability, muscle wasting and weakness, developmental delay, progressive vision loss leading to blindness, swallowing disorders, paralysis and dementia. When clinical symptoms become noticeable, they often appear quickly and progress rapidly in a short period, alternating with a period of stabilization until a symptom is activated again. The child eventually becomes bedridden, unable to speak, unable to swallow, breathing with difficulty. Seizures may occur which gradually disappear over time, spasms are frequent and very painful, the child is still able to smile or respond to the parents at this stage, but eventually they may become blind and generally do not react to the environment. Swallowing eventually becomes difficult and tube feeding becomes necessary. There is no cure, most children with this form of MLD die by the age of 5, often much earlier. Death usually occurs as a result of infections, such as pneumonia, and not from MLD.


It occurs in children aged 4-6 years, motor functions are lost, there is a problem in the child’s behavior, irritability. Inability to walk, dysarthria occurs (difficult speech) and pain in the extremities due to involvement of peripheral nerves.

This form has a slower progression and is recognized by ataxia (it is the loss of the ability to control all or some voluntary muscles of movement, disturbance of balance or coordination of movements) and mental deficit. Death occurs within 10 years from the onset of symptoms.


The onset is between 6-12 years of life, and the symptoms may become clear during the early school years, where a motor disorder or a decline in cognitive functions may indicate the onset of the disease. Symptoms may include incontinence, difficulty walking, slurred speech.

This form of MLD is often presented as a change in personality and behavior, a decline in the ability to learn and work. Attacks can also occur, ie. tremors-muscle shaking and eventually loss of ability to walk. The final stage of the disease is like the late infantile form. The patient often lives to adulthood.


Initial symptoms can appear as early as 14 years of age and appear until 50 years of age as a change in personality, deterioration of the ability to engage in any work, as early dementia with symptoms of psychosis. The initial indications are a change in personality, poor working abilities and emotional lability. The most commonly diagnosed psychiatric disorders are schizophrenia, depression, and the person suffers from MLD. Abuse of alcohol and drugs can also occur in people suffering from MLD. This form progresses more slowly and death can occur several decades after symptoms are detected.

Since the cause of MLD is a deficiency of the enzyme arylsulfatase A (ARSA), a blood test showing a low level of the enzyme indicates Metachromatic Leukodystrophy.

MR (magnetic resonance)

CT (scanner)

DNA testing for the ARSA gene is done in Zagreb.

Nerve biopsy – nerve conduction velocity (electroneurography)

There is currently no cure for MLD. The only treatments are bone marrow or stem cell transplantation, and they are the most effective in slowing down or stopping the disease in people who are in the early stages of the disease, i.e. in the presymptomatic stage. That is why early diagnosis of this disease is very important.