Treatment is limited. Drugs can alleviate the symptoms, such as sleep difficulties and epilepsy. Physiotherapy helps affected children retain the ability to remain upright for as long as possible, and prevents some of the pain.

Recent attempts to treat INCL with cystagon have been unsuccessful.

A painkiller available in several European countries, Flupirtine, has been suggested to possibly slow down the progress of NCL, particularly in the juvenile and late infantile forms. No trial has been officially supported in this venue, however. Currently the drug is available to NCL families either from Germany, Duke University Medical Center in Durham, North Carolina, and the Hospital for Sick Children in Toronto, Ontario.

Currently treatment is only symptomatic and palliative. Treatment for manifestations, such as seizures, dystonia, sleep disorders, depression and anxiety, can be effectively managed. Physical and occupational therapy is recommended to help patients retain fine motor function for as long as possible Recent progress has been made in the application of enzyme-replacement, gene, and stem cell therapies for patients.

On October 20, 2005, the Food and Drug Administration approved a phase I clinical trial of neural stem cells to treat infantile and late infantile Batten disease. Subsequent approval from an independent review board also approved the stem cell therapy in early March 2006. This treatment will be the first ever transplant of fetal stem cells performed on humans. The therapy is being developed by Stem Cells Inc and is estimated to have six patients. The treatment will be carried out in Oregon.

Juvenile NCL has recently been listed on the Federal Clinical Trials website to test the effectiveness of bone marrow/stem cell transplants for this condition. A bone marrow transplant has been attempted in the late infantile form of NCL with disappointing results; while the transplant may have slowed the onset of the disease, the child eventually developed the disease and died in 1998.

Trials testing the effectiveness of bone marrow transplants for infantile NCL in Finland have also been disappointing, with only a slight slowing of disease reported.

There is currently no cure or standard procedure for treatment. A bone marrow transplant has been attempted on a child, but it made no improvement. Hydrocephalus may be seen in younger patients and can be relieved with surgery or by implanting a shunt to relieve pressure.

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.

Infantile convulsions and choreoathetosis (ICCA) syndrome is a neurological genetic disorder with an autosomal dominant mode of inheritance. It is characterized by the association of benign familial infantile epilepsy (BIFE) at age 3–12 months and later in life with paroxysmal kinesigenic choreoathetosis. The ICCA syndrome was first reported in 1997 in four French families from north-western France and provided the first genetic evidence for common mechanisms shared by benign infantile seizures and paroxysmal dyskinesia. The epileptic origin of PKC has long been a matter of debates and PD have been classified as reflex epilepsies.Indeed, attacks of PKC and epileptic seizures have several characteristics in common, they both are paroxysmal in presentation with a tendency to spontaneous remission, and a subset of PKC responds well to anticonvulsants. This genetic disease has been mapped to chromosome 16p-q12. More than 30 families with the clinical characteristics of ICCA syndrome have been described worldwide so far.

Infantile neuronal ceroid lipofuscinoses (INCL) or Santavuori disease or Hagberg-Santavuori disease or Santavuori-Haltia disease or Infantile Finnish type neuronal ceroid lipofuscinosis or Balkan disease is a form of NCL and inherited as a recessive autosomal genetic trait. The disorder is progressive, degenerative and fatal, extremely rare worldwide – with approximately 60 official cases reported by 1982, perhaps 100 sufferers in total today – but relatively common in Finland due to the local founder effect.

Its occurrence is very rare. The infantile form from birth to 2 years of age. The average duration of the infantile form of the illness is usually about 3 years. Onset of the juvenile form presents between two and twelve years of age. Duration of this form is in most cases about 6 years. The adult form from twelve years and older. In younger patients, seizures, megalencephaly, developmental delay, and spasticity are usually present. Neonatal onset is also reported. Onset in adults is least frequent. In older patients, bulbar or pseudobulbar symptoms and spasticity predominate. Symptoms of the adult form may also resemble multiple sclerosis.

There are no more than 500 reported cases.

In affected individuals presenting with the ICCA syndrome, the human genome was screened with microsatellite markers regularly spaced, and strong evidence of linkage with the disease was obtained in the pericentromeric region of chromosome 16, with a maximum lod score, for D16S3133 of 6.76 at a recombination fraction of 0. The disease gene has been mapped at chromosome 16p12-q12.This linkage has been confirmed by different authors. The chromosome 16 ICCA locus shows complicated genomic architecture and the ICCA gene remains unknown.

The prognosis for individuals with Pompe disease varies according to the onset and severity of symptoms. Without treatment the disease is particularly lethal in infants and young children.

Myozyme (alglucosidase alfa) is a recombinant form of the human enzyme acid alpha-glucosidase, and is also currently being used to replace the missing enzyme. In a study which included the largest cohort of patients with Pompe disease treated with enzyme replacement therapy (ERT) to date findings showed that Myozyme treatment clearly prolongs ventilator-free survival and overall survival in patients with infantile-onset Pompe disease as compared to an untreated historical control population. Furthermore, the study demonstrated that initiation of ERT prior to 6 months of age, which could be facilitated by newborn screening, shows great promise to reduce the mortality and disability associated with this devastating disorder. Taiwan and several states in the United States have started the newborn screening and results of such regimen in early diagnosis and early initiation of the therapy have dramatically improved the outcome of the disease; many of these babies have reached the normal motor developmental milestones.

Another factor affecting the treatment response is generation of antibodies against the infused enzyme, which is particularly severe in Pompe infants who have complete deficiency of the acid alpha-glucosidase. Immune tolerance therapy to eliminate these antibodies has improved the treatment outcome.

A Late Onset Treatment Study (LOTS) was published in 2010. The study was undertaken to evaluate the safety and efficacy of aglucosidase alfa in juvenile and adult patients with Pompe disease. LOTS was a randomized, double-blind, placebo-controlled study that enrolled 90 patients at eight primary sites in the United States and Europe. Participants received either aglucosidase alfa or a placebo every other week for 18 months. The average age of study participants was 44 years. The primary efficacy endpoints of the study sought to determine the effect of Myozyme on functional endurance as measured by the six-minute walk test and to determine the effect of aglucosidase alfa on pulmonary function as measured by percent predicted forced vital capacity.

The results showed that, at 78 weeks, patients treated with aglucosidase alfa increased their distance walked in six minutes by an average of approximately 25 meters as compared with the placebo group which declined by 3 meters (P=0.03). The placebo group did not show any improvement from baseline. The average baseline distance walked in six minutes in both groups was approximately 325 meters.

Percent predicted forced vital capacity in the group of patients treated with aglucosidase alfa increased by 1.2 percent at 78 weeks. In contrast, it declined by approximately 2.2 percent in the placebo group (P=0.006).

Infants with Schindler disease tend to die within 4 years of birth, therefore, treatment for this form of the disease is mostly palliative. However, Type II Schindler disease, with its late onset of symptoms, is not characterized by neurological degeneration. There is no known cure for Schindler disease, but bone marrow transplants have been trialed, as they have been successful in curing other glycoprotein disorders.

Cardiac and respiratory complications are treated symptomatically. Physical and occupational therapy may be beneficial for some patients. Alterations in diet may provide temporary improvement but will not alter the course of the disease. Genetic counseling can provide families with information regarding risk in future pregnancies.

On April 28, 2006 the US Food and Drug Administration approved a Biologic License Application (BLA) for Myozyme (alglucosidase alfa, rhGAA), the first treatment for patients with Pompe disease, developed by a team of Duke University researchers. This was based on enzyme replacement therapy using biologically active recombinant human alglucosidase alfa produced in Chinese Hamster Ovary cells. Myozyme falls under the FDA Orphan Drug designation and was approved under a priority review.

The FDA has approved Myozyme for administration by intravenous infusion of the solution. The safety and efficacy of Myozyme were assessed in two separate clinical trials in 39 infantile-onset patients with Pompe disease ranging in age from 1 month to 3.5 years at the time of the first infusion. Myozyme treatment clearly prolongs ventilator-free survival and overall survival. Early diagnosis and early treatment leads to much better outcomes. The treatment is not without side effects which include fever, flushing, skin rash, increased heart rate and even shock; these conditions, however, are usually manageable.

Myozyme costs an average of US$300,000 a year and must be taken for the patients' entire life, so some American insurers have refused to pay for it. On August 14, 2006, Health Canada approved Myozyme for the treatment of Pompe disease. On June 14, 2007 the Canadian Common Drug Review issued their recommendations regarding public funding for Myozyme therapy. Their recommendation was to provide funding to treat a very small subset of Pompe patients (Infants less one year of age with cardiomyopathy). Genzyme received broad approval in the European Union. On May 26, 2010 FDA approved Lumizyme, a similar version of Myozyme, for the treament of late-onset Pompe disease.

A new treatment option for this disease is called Lumizyme. Lumizyme and Myozyme have the same generic ingredient (Alglucosidase Alfa) and manufacturer (Genzyme Corporation). The difference between these two products is in the manufacturing process. Today, the Myozyme is made using a 160-L bioreactor, while the Lumizyme uses a 4000-L bioreactor. Because of the difference in the manufacturing process, the FDA claims that the two products are biologically different. Moreover, Lumizyme is FDA approved as replacement therapy for late-onset (noninfantile) Pompe disease without evidence of cardiac hypertrophy in patients 8 years and older. Myozyme is FDA approved for replacement therapy for infantile-onset Pompe disease.

Recent studies on chaperone molecules to be used with myozyme are starting to show promising results on animal models.

"(current as of January 2017)"

- Shire, with headquarters in Switzerland and a major research center in Lexington, MA, is developing and studying their intrathecal SHP 611 (formerly HGT-1110) ERT [Enzyme Replacement Therapy].

- Clinical Trial

- Recruiting for the clinical trial started January, 2012 and was fully recruited by mid-2014.

- a Fourth cohort was recruited during the first half of 2016. This cohort is fully populated and no new patients are being recruited. Data from this cohort will be gathered by late 2016 with another 3–6 months of outcome analysis expected before a decision is made on what the next drug development and Trial plans will be.

- Phase I/II data is scheduled to be presented in February 2017 at the LDN/WORLD conference.

- Early (post-40 week) results showed the drug was well tolerated at all doses and the 100 mg dose showed the slowest decline in GMFM-88 scores over the trial period. Data continues to be studied.

- Trial Centers

- Trial centers were opened in Europe, South America and Australia

- Patients were successfully recruited in all trial centers

- Inclusion Criteria

- 1st symptoms before age 30 months, currently 7 years old or younger

- Ambulatory – be able to walk 10 steps while holding only one hand.

- Additional clinical trial information & inclusion criteria, can be found on the MLD Foundation website here and at the Clinical Trials.gov site.

- The clinical trial is a 38-week multi-site study of 18 children in three different dosing cohorts. The 'no treatment' placebo arm was removed from the trial in June 2012.

- Patients must go to one of five trial sites for their every other week enzyme infusions: Copenhagen Denmark, Paris France, Tübingen Germany, Sydney Australia, or Porto Alegre Brazil. Derqui, Argentina is awaiting approval.

- A new intrathecal port from a new vendor was approved for use starting December 2013. See the MLD Foundation website for more details.

- SHP611 has "orphan product" status in both Europe and the United States.

- "History:" Shire suspended development of the Metazyme intravenous ERT product in 2010. It was in clinical trial when it was acquired from Zymenex in 2008 (subsequently renamed HGT-1111 by Shire) after it was shown to not have sufficient efficacy by a Phase I/II clinical trial in Europe. The initial study completed September 2008 and the extension study completed October 2010 with the cessation of product supply to trial participants.

Currently, there is no cure for infantile Refsum disease syndrome, nor is there a standard course of treatment. Infections should be guarded against to prevent such complications as pneumonia and respiratory distress. Other treatment is symptomatic and supportive. Patients show variable lifespans with some individuals surviving until adulthood and into old age.

Jansky–Bielschowsky disease is an extremely rare autosomal recessive genetic disorder that is part of the neuronal ceroid lipofuscinosis (NCL) family of neurodegenerative disorders. It is caused by the accumulation of lipopigments in the body due to a deficiency in tripeptidyl peptidase I as a result of a mutation in the TPP1 gene. Symptoms appear between ages 2 and 4 and consist of typical neurodegenerative complications: loss of muscle function (ataxia), drug resistant seizures (epilepsy), apraxia, development of muscle twitches (myoclonus), and vision impairment. This late-infantile form of the disease progresses rapidly once symptoms are onset and ends in death between age 8 and teens. The prevalence of Jansky–Bielschowsky disease is unknown, however NCL collectively affects an estimated 1 in 100,000 individuals worldwide. Jansky–Bielschowsky disease is also known as: late-infantile Batten disease, LINCL, or neuronal ceroid lipofuscinosis.

In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly.

Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. Generally they have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding and breathing problems that can lead to frequent infections, such as pneumonia. Seizures occur in some affected children.

Rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and vision loss due to deterioration (atrophy) of the optic nerve are characteristic of infantile neuroaxonal dystrophy. Hearing loss may also develop. Children with this disorder experience progressive deterioration of cognitive functions (dementia), and eventually lose awareness of their surroundings.

Infantile neuroaxonal dystrophy is characterized by the development of swellings called spheroid bodies in the axons, the fibers that extend from nerve cells (neurons) and transmit impulses to muscles and other neurons. A part of the brain called the cerebellum, which helps to control movements, may also be damaged. In some individuals with infantile neuroaxonal dystrophy, abnormal amounts of iron accumulate in a specific region of the brain called the basal ganglia.

Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills.

As of 2017, data on optimal treatment was limited. Therapies with hormones is the standard of care, namely adrenocorticotrophic hormone (ACTH), or oral

corticosteroids such as prednisone. Vigabatrin is also a common consideration, though there is a risk of visual field loss with long term use. The high cost of ACTH leads doctors to avoid it in the US; higher dose prednisone appears to generate equivalent outcomes.

As of 2017 data from clinical trials of the ketogenic diet for treating infantile spams was inconsistent; most trials were as a second-line therapy after failure of drug treatment, and as of 2017 it had not been explored as a first line treatment in an adequately designed clinical trial.

GM2-gangliosidosis, AB variant is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. It has a similar pathology to Sandhoff disease and Tay-Sachs disease. The three diseases are classified together as the GM2 gangliosidoses, because each disease represents a distinct molecular point of failure in the activation of the same enzyme, beta-hexosaminidase. AB variant is caused by a failure in the gene that makes an enzyme cofactor for beta-hexosaminidase, called the GM2 activator.

AB variant was first observed clinically shortly after the biochemical characterization of Tay-Sachs disease in 1969. The disease was initially thought to be caused by variant alleles of the HEXA gene, and Konrad Sandhoff designated it as AB variant in 1971. Enzyme assay tests of TSD patients revealed a few unusual false negative cases, patients who developed the disease, yet had normal enzyme activity. In other cases, parents who had not tested as carriers for TSD had children who nevertheless became ill with the symptoms of classic infantile TSD.

It was eventually determined that GM2 gangliosidosis could be caused by mutations on three distinct genes, one of which was an activator protein. Disease caused by a mutation that disables this protein was termed AB variant. In 1992, the GM2A gene itself was localized to chromosome 5, and the precise locus was determined the following year.

Pipecolic acidemia, also called hyperpipecolic acidemia or hyperpipecolatemia, is a very rare autosomal recessive metabolic disorder that is caused by a peroxisomal defect.

Pipecolic acidemia can also be an associated component of Refsum disease with increased pipecolic acidemia (RDPA), as well as other peroxisomal disorders, including both infantile and adult Refsum disease, and Zellweger syndrome.

The disorder is characterized by an increase in pipecolic acid levels in the blood, leading to neuropathy and hepatomegaly.

Currently Sandhoff disease does not have any standard treatment and does not have a cure. However, a person suffering from the disease needs proper nutrition, hydration, and maintenance of clear airways. To reduce some symptoms that may occur with Sandhoff disease, the patient may take anticonvulsants to manage seizures or medications to treat respiratory infections, and consume a precise diet consisting of puree foods due to difficulties swallowing. Infants with the disease usually die by the age of 3 due to respiratory infections. The patient must be under constant surveillance because they can suffer from aspiration or lack the ability to change from the passageway to their lungs versus their stomach and their spit travels to the lungs causing bronchopneumonia. The patient also lacks the ability to cough and therefore must undergo a treatment to shake up their body to remove the mucus from the lining of their lungs. Medication is also given to patients to lessen their symptoms including seizures.

Currently the government is testing several treatments including N-butyl-deoxynojirimycin in mice, as well as stem cell treatment in humans and other medical treatments recruiting test patients.

A prenatal diagnosis was made by Kleijer et al. in 1979 by measuring beta-galactosidase and neuraminidase activities in cultured amniotic fluid cells.

Treatment of Aicardi syndrome primarily involves management of seizures and early/continuing intervention programs for developmental delays.

Additional comorbidities and complications sometimes seen with Aicardi syndrome include porencephalic cysts and hydrocephalus, and gastro-intestinal problems. Treatment for porencephalic cysts and/or hydrocephalus is often via a shunt or endoscopic of the cysts, though some require no treatment. Placement of a feeding tube, fundoplication, and surgeries to correct hernias or other gastrointestinal structural problems are sometimes used to treat gastro-intestinal issues.