PKD patients usually show a good response to anticonvulsants. Most commonly used medications are sodium blockers, carbamazepine and phenytoin. During a drug-testing study, patients reported a decreasing response to the latter use of anticonvulsants and switched to carbamazepine or phenytoin. Refraining from established triggers such as sudden movement has been shown to lessen attacks occurrences. Avoidance of predisposing factors such as stress, excitement, and fatigue also help manage attacks.

Currently, no treatment slows the neurodegeneration in any of the neuroacanthocytosis disorders. Medication may be administered to decrease the involuntary movements produced by these syndromes. Antipsychotics are used to block dopamine, anticonvulsants treat seizures and botulinum toxin injections may control dystonia. Patients usually receive speech, occupational and physical therapies to help with the complications associated with movement. Sometimes, physicians will prescribe antidepressants for the psychological problems that accompany neuroacanthocytosis. Some success has been reported with Deep brain stimulation.

Mouthguards and other physical protective devices may be useful in preventing damage to the lips and tongue due to the orofacial chorea and dystonia typical of chorea acanthocytosis.

As there appeared to be a connection with PED and mutated GLUT1 transporters a possible treatment was looking at changing patients diets. A common treatment for another disorder with a mutated GLUT1 transporter is the ketogenic diet. The diet is a strict 3:1 ratio of fat (3) to protein and carbohydrates (1). This diet is thought to help restore the unbalance created by the decreased amount of glucose in the brain caused by the faulty GLUT1 transporter. This diet was administered to three patients who had been screened and found to have mutation in their SLC2A genes coding for GLUT1 and were experiencing PED symptoms. All three showed benefit from this treatment and a reduction in their PED episodes. They were able to exercise and run long distances for the first time in their lives. No other studies have been performed using this diet as many patients feel the advantages of the diet do not outweigh its disadvantages.

As some cases have noted that patients were able to alleviate or lessen their PED attacks with a sugary snack, another diet that was tried on patients was one rich in carbohydrates with additional frequent carbohydrate-containing snacks. Four patients with reported PED symptoms were put on this diet but no observable improvements were noted and in fact one patient even complained of worsening symptoms.

Additionally it has been observed that levodopa may reduce some symptoms associated with PED. This may demonstrate that PED is a precursor to Parkinson's disease. Acetazolamide was beneficial to some patients, but also worsened symptoms in others. Additionally, a modified version of the Atkin's diet helped to regulate glucose levels in the CSF. Patients with PED associated with insulinomas appeared to have symptoms resolved after consuming sugary drinks. Currently, there are no drugs that are particularly useful in completely curing all symptoms.

Treatment for PKND is more difficult than other Paroxysmal Dyskinesias. The majority of patients experience some relief from low dosages of clonazepam, a muscle relaxant and anticonvulsant. Similar to PKD, avoidance of stress, excitement, and fatigue will lower the frequency of PNKD attacks. Many patients also avoid known methyglyoxal containing foods and beverages such as alcohol, coffee, tea, and chocolate.

At the hospital, physicians follow standard protocol for managing seizures. Cluster seizures are generally controlled by benzodiazepines such as diazepam, midazolam, lorazepam or clonazepam. The use of oxygen is recommended in the United States, but in Europe it is only recommended in cases of prolonged epileptic status.

Antiepileptic drugs (AEDs) are used in most cases to control seizures, however, PCDH19 gene-related epilepsy is generally associated with early-onset development of drug resistant seizures. Existing data supports the use of “rational polypharmacy,” which consists of a step-wise addition of AEDs until a patient responds favorably or experiences intolerable adverse events. In general, as in other types of uncontrolled epilepsy, the use of drugs with different mechanisms of action appears to be more effective than combining drugs with similar mechanisms of action.

No currently marketed AEDs have been extensively studied in PCDH19 gene-related epilepsy and there is no established treatment strategy for girls diagnosed with PCDH19 gene-related epilepsy. Patients may respond well to treatment with levetiracetam and in cases of drug resistance, stiripentol, which is not approved in the U.S. but is available through the FDA Expanded Access IND process.

Given the benign nature of the condition and the low seizure frequency, treatment is often unnecessary. If treatment is warranted or preferred by the child and his or her family, antiepileptic drugs can usually control the seizures easily. Carbamazepine is the most frequently used first-line drug, but many other antiepileptic drugs, including valproate, phenytoin, gabapentin, levetiracetam and sultiame have been found effective as well. Bedtime dosing is advised by some. Treatment can be short and drugs can almost certainly be discontinued after two years without seizures and with normal EEG findings, perhaps even earlier.

Parental education about Rolandic epilepsy is the cornerstone of correct management. The traumatizing, sometimes long-lasting effect on parents is significant.

It is unclear if there are any benefits to clobazam over other seizure medications.

There is currently no cure for Costeff syndrome. Treatment is supportive, and thus focuses on management of the symptoms. The resulting visual impairment, spasticity, and movement disorders are treated in the same way as similar cases occurring in the general population.

Patients with ICOE-G need prophylactic treatment mainly with carbamazepine or other antiepileptic drugs licensed for focal seizures. A slow reduction in the dose of medication 2 or 3 years after the last visual or other minor or major seizure should be advised, but if visual seizures reappear, treatment should be restored.

The long-term prognosis of Costeff syndrome is unknown, though it appears to have no effect on life expectancy at least up to the fourth decade of life. However, as mentioned previously, movement problems can often be severe enough to confine individuals to a wheelchair at an early age, and both visual acuity and spasticity tend to worsen over time.

Currently there is no widely accepted treatment that can cure, slow down, or halt the symptoms in the great majority of patients with NCL. However, seizures may be controlled or reduced with use of anti-epileptic drugs. Additionally, physical, speech, and occupational therapies may help affected patients retain functioning for as long as possibleSeveral experimental treatments are under investigation.

Continuous prophylactic antiepileptic drug (AED) treatment may not be needed particularly for children with only 1-2 or brief seizures. This is probably best reserved for children whose seizures are unusually frequent, prolonged, distressing, or otherwise significantly interfering with the child’s life. There is no evidence of superiority of monotherapy with any particular common AED.

Autonomic status epilepticus in the acute stage needs thorough evaluation for proper diagnosis and assessment of the neurologic/autonomic state of the child. "Rescue" benzodiazepines are commonly used to terminate it. Aggressive treatment should be avoided because of the risk of iatrogenic complications, including cardiovascular arrest. There is some concern that intravenous lorazepam and/or diazepam may precipitate cardiovascular arrest. Early parental treatment is more effective than late emergency treatment. Buccal midazolam is probably the first choice medication for out of hospital termination of autonomic status epilepticus which should be administered as soon as the child shows evidence of onset of its habitual autonomic seizures.

Parental education about Panayiotopoulos syndrome is the cornerstone of correct management. The traumatizing, sometimes long-lasting effect on parents is significant particularly because autonomic seizures may last for many hours compounded by physicians’ uncertainty regarding diagnosis, management, and prognosis.

On April 27, 2017, the U.S. Food and Drug Administration approved Brineura (cerliponase alfa) as the first specific treatment for NCL. Brineura is enzyme replacement therapy manufactured through recombinant DNA technology. The active ingredient in Brineura, cerliponase alpha, is intended to slow loss of walking ability in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency. Brineura is administered into the cerebrospinal fluid by infusion via a surgically implanted reservoir and catheter in the head (intraventricular access device).

In those with SS, symptoms typically dramatically improve with low-dose administration of levodopa (L-dopa). L-DOPA exists as a biochemically significant metabolite of the amino acid phenylalanine, as well as a biological precursor of the catecholamine dopamine, a neurotransmitter. (Neurotransmitters are naturally produced molecules that may be sequestered following the propagation of an action potential down a nerve towards the axon terminal, which in turn may cross the synaptic junction between neurons, enabling neurons to communicate in a variety of ways.) Low-dose L-dopa usually results in near-complete or total reversal of all associated symptoms for these patients. In addition, the effectiveness of such therapy is typically long term, without the complications that often occur for those with Parkinson's disease who undergo L-dopa treatment. Thus, most experts indicate that this disorder is most appropriately known as dopa-responsive dystonia (SS).

No data are available on mortality associated with SS, but patients surviving beyond the fifth decade with treatment have been reported. However, in severe, early autosomal recessive forms of the disease, patients have been known to pass away during childhood. Girls seem to be somewhat more commonly affected. The disease less commonly begins during puberty or after age 20, and very rarely, cases in older adults have been reported.

Due to commonly being misdiagnosed, it is common for the disease to remain untreated. When left untreated, patients often need achilles tendon surgery by the age of 21. They will also struggle with walking, an ability that will degrade throughout the day. Power napping can provide temporary relief in untreated patients. It also impairs development into adulthood, reduces balance, and reduces calf muscle development. Socially, it can result in depression, lack of social skills, and inability to find employment.

There are very few reported cases of PED, there are approximately 20 reported sporadic cases of PED and 9 PED families but there is some dispute on the exact number of cases. In addition it appears that PED becomes less severe with aging. Prior to onset of a PED episode some patients reported onset of symptoms including sweating, pallor, and hyperventilation. In brain scans it was observed that patients suffering form frequent PEDs there was increased metabolism in the putamen of the brain and decreased metabolism in the frontal lobe. Another study using subtraction single photon emission computed tomographic (SPECT) imaging technique which was coregistered with an MRI on a patient presented with PED symptoms showed increased cerebral perfusion in the primary somatosensory cortex area, and a mild increase in the region of the primary motor cortex and cerebellum. While all these correlations are not fully understand as to what exactly is happening in the brain it provides areas of interest to study further to hopefully understand PED more fully.

Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

Loss of language and skills related to social interaction and self-care are serious. The affected children face ongoing disabilities in certain areas and require long term care. Treatment of CDD involves both behavior therapy, environmental therapy and medications.

- Behavior therapy: The main aim of Applied Behavior Analysis (ABA) is to systematically teach the child to relearn language, self-care and social skills. The treatment programs designed in this respect "use a system of rewards to reinforce desirable behaviors and discourage problem behavior." ABA programs may be designed by a board-certified specialist in behavior analysis called a "BCBA" (Board Certified Behavior Analyst), but ABA is also widely used by a number of other health care personnel from different fields like psychologists, speech therapists, physical therapists and occupational therapists with differing levels of expertise. Parents, teachers and caregivers are instructed to use these behavior therapy methods at all times.

- Environmental Therapy: Sensory Enrichment Therapy uses enrichment of the sensory experience to improve symptoms in autism, many of which are common to CDD.

- Medications: There are no medications available to directly treat CDD. Antipsychotic medications are used to treat severe behavior problems like aggressive stance and repetitive behavior patterns. Anticonvulsant medications are used to control seizures.

Supportive treatment is the only intervention for acute cerebellar ataxia of childhood. Symptoms may last as long as 2 or 3 months.

An effective treatment has yet to be found. In many cases electrical stimulation of the globus pallidus has been shown to produce improvement of dystonia severity, however it has not been shown to delay neurodegeneration. There is often overlap in the phenotypes of the symptoms both between different NBIA disorders and between NBIA and other disorders, leading to misdiagnoses. Treatments typically treat or ameliorate the symptoms and do not address the accumulation of iron. Psychotherapy, such as dopaminergic drugs, anticholinergics, tetrabenazine, is often used to treat the symptoms but does not improve the long term outcome of the patient.

The group includes the following disorders:

- Pantothenate kinase-associated neurodegeneration (PKAN) also known as neurodegeneration with brain iron accumulation 1 (NBIA1) and Hallervorden–Spatz syndrome

- PLAN (PLA2G6-associated neurodegeneration)

- MPAN (Mitochondrial membrane protein-associated neurodegeneration)

- BPAN (Beta-propeller protein-associated neurodegeneration)

- FAHN (Fatty acid hydroxylase-associated neurodegeneration)

- Kufor–Rakeb syndrome

- Neuroferritinopathy

- Aceruloplasminemia

- Woodhouse–Sakati syndrome

- CoPAN (CoA synthase protein-associated neurodegeneration)

- Idiopathic NBIA

- Neurodegeneration with brain iron accumulation 2B (NBIA2B)

- Neurodegeneration with brain iron accumulation 3 (NBIA3)

Supervised exercise programs have been shown in small studies to improve exercise capacity by several measures.

Oral sucrose treatment (for example a sports drink with 75 grams of sucrose in 660 ml.) taken 30 minutes prior to exercise has been shown to help improve exercise tolerance including a lower heart rate and lower perceived level of exertion compared with placebo.

The prognosis of ICOE-G is unclear, although available data indicate that remission occurs in 50–60% of patients within 2–4 years of onset. Seizures show a dramatically good response to carbamazepine in more than 90% of patients. However, 40–50% of patients may continue to have visual seizures and infrequent secondarily generalized convulsions, particularly if they have not been appropriately treated with antiepileptic drugs.

Courses of treatment for children with is dependent upon the severity of their case. Children with OHS often receive physical and occupational therapy. They may require a feeding tube to supplement nourishment if they are not growing enough. In an attempt to improve the neurological condition (seizures) copper histidine or copper chloride injections can be given early in the child’s life.

However, copper histidine injections have been shown ineffective in studies of copper metabolic-connective tissue disorders such as OHS.

The most common method to manage hypoglycemia and diabetes is with an insulin pump. . However in infants and very young children long acting insulins like Glargine and Levemir are preferred to prevent recurrent hypoglycemia . As soon as parent knows Walcott-Rallison syndrome is the source, treatment or therapy plans need to be drawn up along with frequent check ins to make sure kidney and liver functions are around normal and insulin therapy are working. If needed, the patient can undergo thyroxin therapy in order to maintain proper thyroid stimulating hormone levels. This has only been needed in a few cases were hypothyroidism was present in the patient.

Although there is no known cure for Krabbe disease, bone marrow transplantation has been shown to benefit cases early in the course of the disease. Generally, treatment for the disorder is symptomatic and supportive. Physical therapy may help maintain or increase muscle tone and circulation. Cord blood transplants have been successful in stopping the disease as long as they are given before overt symptoms appear.

Research is underway worldwide to increase scientific understanding of these disorders as well to identify prevention and treatment methods. Known genetic mutations provide a basis for studying some of the conditions.