Treatment remains largely supportive. The behavioral disturbances of MPS-III respond poorly to medication. If an early diagnosis is made, bone marrow replacement may be beneficial. Although the missing enzyme can be manufactured and given intravenously, it cannot penetrate the blood–brain barrier and therefore cannot treat the neurological manifestations of the disease.

Along with many other lysosomal storage diseases, MPS-III exists as a model of a monogenetic disease involving the central nervous system.

Several promising therapies are in development. Gene therapy in particular is under Phase I/II clinical trial in France since October 2011 under the leadership of Paris-based biotechnology company Lysogene. Other potential therapies include chemical modification of deficient enzymes to allow them to penetrate the blood–brain barrier, stabilisation of abnormal but active enzyme to prevent its degradation, and implantation of stem cells strongly expressing the missing enzyme. For any future treatment to be successful, it must be administered as early as possible. Currently MPS-III is mainly diagnosed clinically, by which stage it is probably too late for any treatment to be very effective. Neonatal screening programs would provide the earliest possible diagnosis.

The flavonoid genistein decreases the pathological accumulation of glycosaminoglycans in Sanfilippo syndrome. "In vitro", animal studies and clinical experiments suggest that the symptoms of the disease may be alleviated by an adequate dose of genistein. Despite its reported beneficial properties, genistein also has toxic side effects.

Several support and research groups have been established to speed the development of new treatments for Sanfilippo syndrome.

Enzyme replacement therapies are currently in use. BioMarin Pharmaceutical provides therapeutics for mucopolysaccaradosis type I (MPS I), by manufacturing laronidase (Aldurazyme), commercialized by Genzyme. Enzyme replacement therapy has proven useful in reducing non-neurological symptoms and pain.

Bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) can be used as treatments for MPS. Abnormal physical characteristics, except for those affecting the skeleton and eyes, can be improved, and neurologic degeneration can often be halted. BMT and UCBT are high-risk procedures with high rates of morbidity and mortality. No cure for MPS I is known.

Currently there is no cure for these disorders. Medical care is directed at treating systemic conditions and improving the person's quality of life. Physical therapy and daily exercise may delay joint problems and improve the ability to move.

Changes to the diet will not prevent disease progression, but limiting milk, sugar, and dairy products has helped some individuals experiencing excessive mucus.

Surgery to remove tonsils and adenoids may improve breathing among affected individuals with obstructive airway disorders and sleep apnea. Sleep studies can assess airway status and the possible need for nighttime oxygen. Some patients may require surgical insertion of an endotrachial tube to aid breathing. Surgery can also correct hernias, help drain excessive cerebrospinal fluid from the brain, and free nerves and nerve roots compressed by skeletal and other abnormalities. Corneal transplants may improve vision among patients with significant corneal clouding.

Enzyme replacement therapy (ERT) are currently in use or are being tested. Enzyme replacement therapy has proven useful in reducing non-neurological symptoms and pain. Currently BioMarin Pharmaceutical produces enzyme replacement therapies for MPS type I and VI. Aldurazyme is an enzymatic replacement therapy for alpha-L-iduronidase produced by BioMarin for use in Type I MPS. In July 2006, the United States Food and Drug Administration approved a synthetic version of I2S produced by Shire Pharmaceuticals Group, called Elaprase, as a treatment for MPS type II (Hunter syndrome).

Bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) have had limited success in treating the mucopolysaccharidoses. Abnormal physical characteristics, except for those affecting the skeleton and eyes, may be improved, but neurologic outcomes have varied. BMT and UCBT are high-risk procedures and are usually performed only after family members receive extensive evaluation and counseling.

For information on clinical trials visit Clinical Trials Search

Due to the nature of the illness, and absence of a really efficient treatment, it is important to emphasize the need for extensive palliative treatment against the diverse symptoms. Their objective is to reduce the effects of the deterioration of many bodily functions. In light of the diversity of symptoms, it is quite common to use a wide spectrum of palliative strategies where surgery and therapies are often pivotal.

For a long time, the most efficient approach had been to use bone marrow graft, or hematopoietic stem cell transplantation. They each have the advantage of providing a new source of the missing I2S. However, the results have been considered imperfect at best.

While this treatment alternative is able to improve or stop the progression of some of the so-called "physical" symptoms, it does not prevent the eventual cognitive regression that occurs in Hunter syndrome patients who are cognitively affected, although it may slow such regression early on. Therefore, for attenuated patients, this may still serve as a viable treatment option because of its more permanent nature, possibly even equivalent to weekly enzyme replacement therapy, resulting in much improved life expectancy.

However, even for attenuated patients, it is a major intervention with significant mortality risks and potential for life-threatening or altering complications such as graft-versus-host disease. For cognitively affected patients, without solving the challenge of cognitive regression, at best it is limited as a permanent treatment alternative. Because of all these reasons, bone marrow grafts or hematopoietic stem cell transplantation have seen a decrease in their application as Hunter syndrome treatment.

No cures for lysosomal storage diseases are known, and treatment is mostly symptomatic, although bone marrow transplantation and enzyme replacement therapy (ERT) have been tried with some success. ERT can minimize symptoms and prevent permanent damage to the body. In addition, umbilical cord blood transplantation is being performed at specialized centers for a number of these diseases. In addition, substrate reduction therapy, a method used to decrease the production of storage material, is currently being evaluated for some of these diseases. Furthermore, chaperone therapy, a technique used to stabilize the defective enzymes produced by patients, is being examined for certain of these disorders. The experimental technique of gene therapy may offer cures in the future.

Ambroxol has recently been shown to increase activity of the lysosomal enzyme glucocerebrosidase, so it may be a useful therapeutic agent for both Gaucher disease and Parkinson's disease. Ambroxol triggers the secretion of lysosomes from cells by inducing a pH-dependent calcium release from acidic calcium stores. Hence, relieving the cell from accumulating degradation products is a proposed mechanism by which this drug may help.

The treatment for Morquio syndrome consists of prenatal identification and of enzyme replacement therapy. On 12 February 2014, the US Food and Drug Administration approved the drug elosulfase alfa (Vimizim) for treating the disease.

There are no specific treatments for lipid storage disorders; however, there are some highly effective enzyme replacement therapies for people with type 1 Gaucher disease and some patients with type 3 Gaucher disease. There are other treatments such as the prescription of certain drugs like phenytoin and carbamazepine to treat pain for patients with Fabry disease. Furthermore, gene thereapies and bone marrow transplantation may prove to be effective for certain lipid storage disorders. Diet restrictions do not help prevent the buildup of lipids in the tissues.

There is currently no therapy or cure for MLD in late infantile patients displaying symptoms, or for juvenile and adult onset with advanced symptoms. These patients typically receive clinical treatment focused on pain and symptom management.

Pre-symptomatic late infantile MLD patients, as well as those with juvenile or adult MLD that are either presymptomatic or displaying mild symptoms, can consider bone marrow transplantation (including stem cell transplantation), which may slow down progression of the disease in the central nervous system. However, results in the peripheral nervous system have been less dramatic, and the long-term results of these therapies have been mixed. Recent success has involved stem cells being taken from the bone marrow of children with the disorder and infecting the cells with a retro-virus, replacing the stem cells' mutated gene with the repaired gene before re-injecting it back into the patient where they multiplied. The children by the age of five were all in good condition and going to kindergarten when normally by this age, children with the disease can not even speak.

Several therapy options are currently being investigated using clinical trials primarily in late infantile patients. These therapies include gene therapy, enzyme replacement therapy (ERT), substrate reduction therapy (SRT), and potentially enzyme enhancement therapy (EET).

A team of international researchers and foundations gathered in 2008 to form an international MLD Registry to create and manage a shared repository of knowledge, including the natural history of MLD. This consortium consisted of scientific, academic and industry resources. This registry never became operational.

With many different types of leukodystrophies and causes, treatment therapies vary for each type. Many studies and clinical trials are in progress to find treatment and therapies for each of the different leukodystrophies. Stem cell transplants and gene therapy appear to be the most promising in treating all leukodystrophies providing it is done as early as possible.

For hypomyelinating leukodystrophies, therapeutic research into cell-based therapies appears promising. Oligodendrocyte precursor cells and neural stem cells have been transplanted successfully and have shown to be healthy a year later. Fractional anisotropy and radial diffusivity maps showed possible myelination in the region of the transplant. Induced pluripotent stem cells, oligodendrocyte precursor cells, gene correction, and transplantation to promote the maturation, survival, and myelination of oligodendrocytes seem to be the primary routes for possible treatments.

For three types of leukodystrophies (X-linked adrenoleukodystrophy (X-ALD), metachromatic leukodystrophy (MLD) and Krabbe Disease (globoid cell leukodystrophy - GLD), gene therapy using autologous hematopoietic stem cells to transfer the disease gene with lentiviral vectors have shown to be successful and are currently being used in clinical trials for X-ALD and MLD. The progression of X-ALD has shown to be disrupted with hematopoietic stem cell gene therapy but the exact reason why demyelination stops and the amount of stem cells needed is unclear. While there is an accumulation of very long chain fatty acids in the brain, it does not seem to be the reason behind the disease as gene therapy does not correct it.

Adeno-associated vectors have also been used in intracerebral injections to treat MLD. In some patients with MLD, their IQ increased, nerve conduction improved, their MRIs appeared stable, and had normal enzyme levels. Although the greater majority of patients seem to improve after the transplant, some do not respond well to treatment, which may cause devastating outcomes. For those leukodystrophies that result from a deficiency of lysozyme enzymes, such as Krabbes disease, enzyme replacement therapy seems hopeful, however, this proves difficult as the blood-brain barrier severely limits what can pass through into the central nervous system. Due to this obstacle, most research and clinical trials are turning to allogeneic hematopoietic stem cell transplantation.

A great deal of interest exists in treating MPS I with gene therapy. This approach has been taken with retroviral, lentiviral, adeno-associated virus, and even nonviral vectors to deliver the iduronidase gene. Successful treatments of the mouse, dog, and cat models of MPS I have occurred and may pave the way for future human trials.

Because XLI is caused by a gene mutation or deletion, there is no "cure." One of the aims of treatment is to reduce scaling by removing the excess, flaky scales, and keep the skin hydrated. This can be achieved using a variety of topical creams.

- Keratolytic agents such as Ammonium lactate (Lac-Hydrin) are used to facilitate the release of retained corneocytes.

- Topical isotretinoin

- The topical receptor-selective retinoid tazarotene

Research is ongoing with regard to the use of gene therapy to treat XLI.

"(current as of January 2017)"

Two different approaches to gene therapy are currently being researched for MLD.

- Gene therapy with an autologous stem cell transplant – Italian researchers at the San Raffaele Telethon Institute tested a novel approach combining gene therapy with a stem cell transplant. Recruiting for the Phase I/II Clinical Trial formally started on March 24, 2010 after approval from the Italian Authorities. Recruiting the initial cohort of 8 patients was completed in mid-March 2013. The trial was to test the efficacy and safety of autologous (using the patient's own cells) hematopoietic stem cell transplantation (HSCT) after genetic modification to deliver a super-therapeutic (over-expressing) ARSA enzyme to the nervous system by the route of the blood cells. Using the patient's own stem cells with genetic correction should reduce or eliminate the complications of graft vs. host disease and provide a long term solution to proper ARSA expression in MLD patients. Bench and animal tests showed positive results. The researchers published 2-year outcomes for the first three patients in July 2013. Results were described as promising.

- The Phase I/II clinical trial is complete. No additional patients are being recruited while the data is analyzed and work progresses to improve the manufacturability and repeatable of the technology while an expansion to other geographies to increase access is being considered.

- Recruiting was completed for the 20 patient cohort in April 2015, which includes an expansion in December 2014 to add 6 additional patients.

- Inclusion criteria are pre-symptomatic late infantiles and both pre- and early-symptomatic juveniles. See details on inclusion criteria and the trial protocol here.

- The trial was at a single center at the San Raffaele Institute in Milan, Italy. All costs were to be paid by the researchers. This was a 3-year study. In March 2013, the last of the 8 primary trial patients started therapy. The trial had several compassionate access patients and ultimately was expanded to 20 patients"

- In late 2013 GSK exercised its option for the San Rafaelle gene therapy technology and is working with the Milan Investigators to prepare for the next phase of study.

- Intracerebral Gene therapy – A Phase I/II Clinical Trial started recruiting in Paris in late March, 2013 for an Intracerebral Gene Therapy clinical trial where special "vectors" carrying genetically modified material are directly injected into a dozen sites in the brain. The hope is that the corrected cells and the enzyme they produce will then diffuse into surrounding areas of the brain. Extensive work in the lab and some encouraging ALD studies provided the basis for this trial.

- Recruiting 5 late infantiles between the ages of 6 and 48 months for a two-year study

- Must have first shown symptoms in the last 12 months

- Additional trial inclusion criteria and information can be found here

CDPX1 activity may be inhibited by warfarin because it is believed that ARSE has enzymatic activity in a vitamin K producing biochemical pathway. Vitamin K is also needed for controlling binding of calcium to bone and other tissues within the body.

Sanfilippo syndrome, or mucopolysaccharidosis III (MPS-III) is a rare autosomal recessive lysosomal storage disease. It is caused by a deficiency in one of the enzymes needed to break down the glycosaminoglycan heparan sulfate (which is found in the extra-cellular matrix and on cell surface glycoproteins).

Although undegraded heparan sulfate is the primary stored substrate, glycolipids such as gangliosides are also stored despite no genetic defect in the enzymes associated with their breakdown.

The condition is named for Sylvester Sanfilippo, the pediatrician who first described the disease.

MPS II, Hunter syndrome or iduronate sulfatase deficiency, is caused by lack of the enzyme iduronate sulfatase. Hunter syndrome has two clinical subtypes and (since it shows X-linked recessive inheritance) is the only one of the mucopolysaccharidoses in which the mother alone can pass the defective gene to a son. The incidence of Hunter syndrome is estimated to be 1 in 100,000 to 150,000 male births.

MLD Foundation provides updates on MLD research, including (as of 2017) three clinical trials evaluating gene therapy and enzyme replacement therapy, and various lines of basic research. They are also active in newborn screening.

The Global Leukodystrophy Initiative was formed in 2013 to bring together clinicians, researchers and advocacy groups to focus and improve both clinical care and research.

In addition, many research groups are studying the cellular processes of myelination, which may provide insights into leukodystrophy. Researchers in New York have successfully cured leukodystrophy in mice, using skin cells to repair damaged myelin sheaths. Researchers hypothesize that this treatment may possibly be used in curing human multiple sclerosis.

Multiple sulfatase deficiency (also known as "Austin disease", and "mucosulfatidosis") is a very rare autosomal recessive lysosomal storage disease caused by a deficiency in multiple sulfatase enzymes, or in formylglycine-generating enzyme, which activates sulfatases. It is similar to mucopolysaccharidosis.

The majority of patients is initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis. In some families where the disease-causing mutations are known and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders.

Morquio syndrome (referred to as mucopolysaccharidosis IV, MPS IV, Morquio-Brailsford syndrome, or Morquio) is a rare metabolic disorder in which the body cannot process certain types of mucopolysaccharides. This birth defect, which is autosomal recessive, is thus a lysosomal storage disorder that is usually inherited. In the US, the incidence rate for Morquio is estimated at between 1 in 200,000 and 1 in 300,000 live births.

The build-up or elimination of mucopolysaccharides, rather than processing by their usual biochemical pathways, causes various symptoms. These involve accumulation of keratan sulfate.

Symptoms of this disorder commonly appear between one and two years of age. Symptoms include mildly coarsened facial features, deafness, ichthyosis and an enlarged liver and spleen (hepatosplenomegaly). Abnormalities of the skeleton, such as a curving of the spine and breast bone may occur. The skin of individuals afflicted with this disorder, is typically dry. Children affected by this disorder develop more slowly than normal and may display delayed speech and walking skills.

The disease is fatal, with symptoms that include neurological damage and severe mental retardation. These sulfatase enzymes are responsible for breaking down and recycling complex sulfate-containing sugars from lipids and mucopolysaccharides within the lysosome. The accumulation of lipids and mucopolysaccharides inside the lysosome results in symptoms associated with this disorder. Worldwide, forty cases of Multiple Sulfatase Deficiency have been reported to date.

Children with Maroteaux–Lamy syndrome usually have normal intellectual development but share many of the physical symptoms found in Hurler syndrome. Caused by the deficient enzyme N-acetylgalactosamine 4-sulfatase, Maroteaux–Lamy syndrome has a variable spectrum of severe symptoms. Neurological complications include clouded corneas, deafness, thickening of the dura (the membrane that surrounds and protects the brain and spinal cord), and pain caused by compressed or traumatized nerves and nerve roots.

Signs are revealed early in the affected child's life, with one of the first symptoms often being a significantly prolonged age of learning how to walk. By age 10 children have developed a shortened trunk, crouched stance, and restricted joint movement. In more severe cases, children also develop a protruding abdomen and forward-curving spine. Skeletal changes (particularly in the pelvic region) are progressive and limit movement. Many children also have umbilical hernia or inguinal hernias. Nearly all children have some form of heart disease, usually involving valve dysfunction.

An enzyme replacement therapy, galsulfase (Naglazyme), was tested on patients with Maroteaux–Lamy syndrome and was successful in that it improved growth and joint movement. An experiment was then carried out to see whether an injection of the missing enzyme into the hips would help the range of motion and pain. At a cost of $365,000 a year, Naglazyme is one of the world's most expensive drugs.

The GM1 gangliosidoses (or GM1 gangliosidos"i"s) are caused by a deficiency of beta-galactosidase, with resulting abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells.

GM1 Gangliosidoses are inherited, autosomal recessive sphingolipidoses, resulting from marked deficiency of Acid Beta Galactosidase.

A lipid storage disorder (or lipidosis) can be any one of a group of inherited metabolic disorders in which harmful amounts of fats or lipids accumulate in some of the body’s cells and tissues. People with these disorders either do not produce enough of one of the enzymes needed to metabolize and break down lipids or they produce enzymes that do not work properly. Over time, this excessive storage of fats can cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system, liver, spleen and bone marrow.

Inside cells under normal conditions, lysosomes convert, or metabolize, lipids and proteins into smaller components to provide energy for the body.

Surgical excision is performed when exostoses lead to growth disturbances or lead to disability. Knee osteotomies are associated with high incidence of peroneal nerve paralysis.

Surgery, physical therapy and pain management are currently the only options available to HME patients, but success varies from patient to patient and many struggle with pain, fatigue and mobility problems throughout their lives.

It is not uncommon for HME patients to undergo numerous surgical procedures throughout their lives to remove painful or deforming exostoses, correct limb length discrepancies or improve range of motion. Usually the treatment can be problematic. The osteochondromas can return in the same places and may be more painful.