MLD 101 – A Layperson's Overview

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This page provides a quick overview of MLD.  Each section has a link to access additional details and explanation.  


MLD is short for metachromatic leukodystrophy. Translated from doctor talk MLD means: meta – change, chromatic – color, leuko – white matter, dystrophy – degeneration. 

MLD’s name therefore comes from degeneration in the white matter of the brain and Central Nervous System (CNS) which has a color on staining that should not be there. Staining was how the disease was observed before the advent of the MRI.


Basically people who are affected by MLD lack an enzyme in their blood called Arylsulfatase-A, (ARSA). Without this enzyme, sulfatides are NOT broken down and instead build-up in the white matter of the brain (CNS) and peripheral nervous system  (PNS) causing destruction of the myelin sheath, or demyelination. Without an intact myelin sheath there is a breakdown in communication between the nerves and the brain. This loss of or miscommunication accounts for the loss of acquired functions, paralysis, blindness, seizures and eventual death seen in MLD.

Types of MLD

Generally, there are considered to be three main types of MLD that have different ages of onset: late-infantile, juvenile, and adult. The late-infantile form of MLD is the most commonly observed form of MLD. 

Saposin B Deficiency is a very rare form of MLD where the ARSA enzyme levels are OK, but the activator for those enzymes is missing or low. The symptoms are identical to MLD, but disease altering therapies will be different.

Those with Multiple Sulfatase Deficiency (MSD) (sometimes refered to as Austin’s Disease) have an activation deficiency that affects many enzymes, including ARSA. The clinical symptoms often look like MLD, but the disease biology and therapies are different.

MLD is not contagious and can not be passed to others through any sort of physical contact – it is a genetic condition.

Therapies & Research

At this time there is no cure for MLD. The only widely available treatment today is stem cell transplant (SCT or HSCT), the successor to bone marrow transplant.  Transplant is most effective in slowing the disease in people who are not showing any symptoms of MLD (pre-symptomatic). New therapies are coming!  

MLD’s first Gene Therapy (GT) is being reviewed by the EMA in Europe and will be submitted for review by the FDA at the end of 2020. 

Enzyme Replacement Therapy (ERT), and signficant advances in stem cell transplants are in clinical trial.  Another gene theapy is preapring for clinical trial. 

More therapy details here.


MLD is an autosomal recessive genetic defect. Translated this means both males and females carry the gene and both parents need to carry the defective gene in order to have an affected child.

There are nearly 300 differnt mutations that are known or suspected to cause MLD. A very small handful of these mutationsmake up the great majorty of MLD cases.Our experience, however, is the most frequent form of MLD, infantile onset, is often not diagnosed properly prior to significant disease progression and later onsets of MLD are often misdiagnosed as ADHD, ADD, or psychiatric conditions and hence the frequency might be higher than reported.

Incidence and Prevalence

It is estimated that 1 in 100 of the general population are carriers and the affected birth rate is 1:40,000 – thus MLD gets its designation of being a rare disease.

We estimate that approximately 2,000 new late infantile babies are born each year (including 60 in the US and 100 in Europe) and there are approximately 49,000 people alive at any given time with all forms of MLD worldwide. We have a video with more details tables you can view here.(Source: MLD Foundation 2017-01)

More incidence details here.



The first report of MLD was in 1933 and is commonly credited to Dr. Joseph Godwin Greenfield,(1884-1958) a professor of pathology and clinical medicine at what is now the National Hospital for Neurology & Neurosurgery in London – the same campus as what is now the Great Ormond Street Hospital for Children.

MLD was first called Greenfield’s disease. The first published medical reports of MLD appeared in the early 1960’s with the first experimental bone marrow transplants treatments in the early 1980’s.

Testing & Diagnosis of MLD

The diagnosis of MLD is fairly straightforward once you know what you are looking for. Unfortunately, it is often after many misdiagnosis, and often after the disease is very progressed when the MLD sufferer is put in contact with staff that knows of MLD and performs the proper testing. Common misdiagnosis for MLD include Cerebral Palsy, Batton’s Disease, and ADHD – especially with children. In adults since the presentation is often first psychological, not physical, the misdiagnosis can be a variety of psychological conditions.

MRI can indicate white matter disease (or leukodystrophy) and can suggest MLD, but a MRI alone is not a definitive diagnostic tool for MLD.

Usually a blood test is done first to check for enzyme levels, followed by a urine test to confirm the presence of sulfatides.

Types of MLD – Onset/Progression

Late Infantile is estimated to be 50-60% of the diagnosis’ and usually presents after normal development during a baby’s first 12-18 months followed delay or regression of motor milestones. 

Juvenile Onset is usually between ages 4-14. Onset usually starts with either motor or cognitive symptoms.

Adult Onset is characterized by normal development through puberty, and then symptoms present at some later age – generally from the 20’s through the 40’s. The initial adult onset signs are often changes cognitive abilities and personality.

Is there a cure? – Treatments & Therapies

Today there is no cure for Metachromatic Leukodystrophy, MLD. Research is underway pursuing several new therapies, but there is no cure on the near-term horizon.

The only treatment (therapy) at present anywhere for anyone is a stem cell (SCT) or bone marrow transplant(BMT). But today’s successful stem cell or bone marrow transplant (BMT) is not a cure for MLD – at best it slows further deterioration by replacing the bad marrow with “good” marrow that can produce the missing enzyme.