Succinic acid has been studied, and shown effective for both Leighs disease, and MELAS syndrome. If the mutation is in succinate dehydrogenase then there is a build up of succinate, in which case succinic acid won't work so the treatment is with fumaric acid to replace the fumarate than can not be made from succinate. A high-fat, low-carbohydrate diet may be followed if a gene on the X chromosome is implicated in an individual's Leigh syndrome. Thiamine (vitamin B) may be given if a deficiency of pyruvate dehydrogenase is known or suspected. The symptoms of lactic acidosis are treated by supplementing the diet with sodium bicarbonate (baking soda) or sodium citrate, but these substances do not treat the cause of Leigh syndrome. Dichloroacetate may also be effective in treating Leigh syndrome-associated lactic acidosis; research is ongoing on this substance. Coenzyme Q10 supplements have been seen to improve symptoms in some cases.

Clinical trials of the drug EPI-743 for Leigh disease are ongoing.

In 2016, John Zhang and his team at New Hope Fertility Center in New York, USA, performed a spindle transfer mitochondrial donation technique on a mother in Mexico who was at risk of producing a baby with Leigh disease. A healthy boy was born on 6 April 2016. However, it is not yet certain if the technique is completely reliable and safe.

There is no treatment for NBS, however in those with agammaglobulinemia, intravenous immunoglobulin may be started. Prophylactic antibiotics are considered to prevent urinary tract infections as those with NBS often have congenital kidney malformations. In the treat of malignancies radiation, alkylating antineoplastic agents, and epipodophyllotoxins are not used, and methotrexate can be used with caution and, the dose should be limited. Bone marrow transplants and hematopoietic stem cells transplants are also considered in the treatment of NBS. The supplementation of Vitamin E is also recommended. A ventriculoperitoneal shunt can be placed in patients with hydrocephaly, and surgical intervention of congenital deformities is also attempted.

Treatment is symptomatic. There is no standard course of treatment for Sotos syndrome.

Vestronidase alfa-vjbk (Mepsevii) is the only drug approved by U.S. Food and Drug Administration for the treatment of pediatric and adult patients.

There is no cure available for Weaver syndrome. However, with multidisciplinary management such as neurological, pediatric, orthopedic, and psychomotor care and genetic counseling, symptoms can be managed. Surgery may be used to correct any skeletal issues. Physical and occupational therapy are considered an option to help with muscle tone. Also, speech therapy is often recommended for speech related problems.

Sotos syndrome is not a life-threatening disorder and patients may have a normal life expectancy. Developmental delays may improve in the school-age years; however, coordination problems may persist into adulthood, along with any learning disabilities and/or other physical or mental issues.

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.

With appropriate treatment and management, patients with Weaver syndrome appear to do well, both physically and intellectually, throughout their life and have a normal lifespan. Their adult height is normal as well.

Several medications are used to improve bile flow, including ursodiol (Actigall).These medications differ in their rates of success.

Certain drugs may be used to reduce itching (pruritus): hydroxyzine (Atarax), cholestyramine, rifampicin, phenobarbital, and naltrexone. Similar to the medications which improve bile flow, the anti-itching drugs vary in their success rate.

Many patients with Alagille syndrome will also benefit from a high dose of a multivitamin such as ADEK (continuing high levels of vitamins A, D, E, and K), as the reduced bile flow makes it difficult to absorb and utilize these vitamins.

Early treatment is possible once the disease is detected. Once the classical symptoms appear, the best way to eliminate the dangers of Alagille syndrome is a full liver transplant. Most of the short-term treatments available are aimed at improving the functioning of the heart and reducing the effects of impaired liver, kidney, and spleen function.

NARP syndrome is not curable. Symptomatic relief is targeted. Antioxidants play a role in improving the oxidative phosphorylation that is otherwise impaired.

In addition to measures for chronic kidney disease (CKD) of any cause, there is evidence that ACE inhibitors can slow the deterioration of kidney function in Alport syndrome, delaying the need for dialysis or transplantation. The development of proteinuria has been recommended as an indication for commencing treatment.

Once kidney failure has developed, patients usually do well on dialysis or with a kidney transplant. Very rarely the Alport molecule in the donor kidney causes an aggressive immune response in the recipient, 'Alport post-transplant anti-GBM disease'.

Gene therapy has been frequently discussed, but delivering it to the podocytes in the glomerulus that normally produce the type IV collagen in the glomerular basement membrane is challenging.

It is not known whether ACE inhibitors or other treatments affect hearing loss. For those with classic Alport syndrome, hearing aids are often required in teenage or young adult years.

Although research is ongoing, treatment options are currently limited; vitamins are frequently prescribed, though the evidence for their effectiveness is limited.

Pyruvate has been proposed in 2007 as a treatment option. N-acetyl cysteine reverses many models of mitochondrial dysfunction.. In the case of mood disorders, specifically bipolar disorder, it is hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options.

Hormonal suppressive therapy with luteinizing hormone receptor agonists like leuprolide can be used to treat the seizure component, and are effective in most patients.

Surgery is offered if there is failure of medical therapy or rapid growth of lesion, with specific options including stereotactic thermocoagulation, gamma knife radiosurgery, and physical resection by transsphenoidal microsurgery. Surgical response is typically better when the seizure focus has been found by EEG to originate in or near the mass. The specific location of the lesion relative to the pituitary and infundibulum and the amount of hormonal disturbance at presentation can help predict risk of hypopituitarism following surgery.

In secondary cases, treatment of the cause, where possible, is indicated. Additionally, treatment for HLH itself is usually required.

While optimal treatment of HLH is still being debated, current treatment regimes usually involve high dose corticosteroids, etoposide and cyclosporin. Intravenous immunoglobulin is also used. Methotrexate and vincristine have also been used. Other medications include cytokine targeted therapy.

An experimental treatment, an anti IFN-gamma monoclonal antibody tentatively named NI-0501, is in clinical trials for treating primary HLH. The FDA awarded breakthrough drug status to NI-0501 in 2016.

Spindle transfer, where the nuclear DNA is transferred to another healthy egg cell leaving the defective mitochondrial DNA behind, is a potential treatment procedure that has been successfully carried out on monkeys. Using a similar pronuclear transfer technique, researchers at Newcastle University led by Douglass Turnbull successfully transplanted healthy DNA in human eggs from women with mitochondrial disease into the eggs of women donors who were unaffected. In such cases, ethical questions have been raised regarding biological motherhood, since the child receives genes and gene regulatory molecules from two different women. Using genetic engineering in attempts to produce babies free of mitochondrial disease is controversial in some circles and raises important ethical issues. A male baby was born in Mexico in 2016 from a mother with Leigh syndrome using spindle transfer.

In September 2012 a public consultation was launched in the UK to explore the ethical issues involved. Human genetic engineering was used on a small scale to allow infertile women with genetic defects in their mitochondria to have children.

In June 2013, the United Kingdom government agreed to develop legislation that would legalize the 'three-person IVF' procedure as a treatment to fix or eliminate mitochondrial diseases that are passed on from mother to child. The procedure could be offered from 29 October 2015 once regulations had been established.

Embryonic mitochondrial transplant and protofection have been proposed as a possible treatment for inherited mitochondrial disease, and allotopic expression of mitochondrial proteins as a radical treatment for mtDNA mutation load.

Currently, human clinical trials are underway at GenSight Biologics (ClinicalTrials.gov # NCT02064569) and the University of Miami (ClinicalTrials.gov # NCT02161380) to examine the safety and efficacy of mitochondrial gene therapy in Leber's hereditary optic neuropathy.

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.

Standard of care for treatment of CPT II deficiency commonly involves limitations on prolonged strenuous activity and the following dietary stipulations:

- The medium-chain fatty acid triheptanoin appears to be an effective therapy for adult-onset CPT II deficiency.

- Restriction of lipid intake

- Avoidance of fasting situations

- Dietary modifications including replacement of long-chain with medium-chain triglycerides supplemented with L-carnitine

There is no cure, although curative therapy with bone marrow transplantion is being investigated in clinical trials. It is believed the healthy marrow will provide the sufferer with cells from which osteoclasts will develop. If complications occur in children, patients can be treated with vitamin D. Gamma interferon has also been shown to be effective, and it can be associated to vitamin D. Erythropoetin has been used to treat any associated anemia. Corticosteroids may alleviate both the anemia and stimulate bone resorption. Fractures and osteomyelitis can be treated as usual. Treatment for osteopetrosis depends on the specific symptoms present and the severity in each person. Therefore, treatment options must be evaluated on an individual basis. Nutritional support is important to improve growth and it also enhances responsiveness to other treatment options. A calcium-deficient diet has been beneficial for some affected people.

Treatment is necessary for the infantile form:

- Vitamin D (calcitriol) appears to stimulate dormant osteoclasts, which stimulates bone resorption

- Gamma interferon can have long-term benefits. It improves white blood cell function (leading to fewer infections), decreases bone volume, and increases bone marrow volume.

- Erythropoietin can be used for anemia, and corticosteroids can be used for anemia and to stimulate bone resorption.

Bone marrow transplantation (BMT) improves some cases of severe, infantile osteopetrosis associated with bone marrow failure, and offers the best chance of longer-term survival for individuals with this type.

In pediatric (childhood) osteopetrosis, surgery is sometimes needed because of fractures. Adult osteopetrosis typically does not require treatment, but complications of the condition may require intervention. Surgery may be needed for aesthetic or functional reasons (such as multiple fractures, deformity, and loss of function), or for severe degenerative joint disease.

The long-term-outlook for people with osteopetrosis depends on the subtype and the severity of the condition in each person.The severe infantile forms of osteopetrosis are associated with shortened life expectancy, with most untreated children not surviving past their first decade. seems to have cured some infants with early-onset disease. However, the long-term prognosis after transplantation is unknown. For those with onset in childhood or adolescence, the effect of the condition depends on the specific symptoms (including how fragile the bones are and how much pain is present). Life expectancy in the adult-onset forms is normal.

Currently no effective treatment exists for kernicterus. Future therapies may include neuroregeneration. A handful of patients have undergone deep brain stimulation, and experienced some benefit. Drugs such as baclofen, clonazepam, and artane are often used to manage movement disorders associated with kernicterus. Proton pump inhibitors are also used to help with reflux. Cochlear implants and hearing aids have also been known to improve the hearing loss that can come with kernicterus (auditory neuropathy - ANSD).

The severity and prognosis vary with the type of mutation involved.

Treatment is depended on the type of glycogen storage disease. E.g. GSD I is typically treated with frequent small meals of carbohydrates and cornstarch to prevent low blood sugar, while other treatments may include allopurinol and human granulocyte colony stimulating factor.

Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an under-recognized inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who first described the condition in 1951.

Antihistamines are not effective in treating the hives in this condition. It may respond to immunosuppressant drugs such as corticosteroids, cyclooxygenase inhibitors, interferon alpha, interleukin 1 receptor antagonists (Anakinra), perfloxacin, colchicine, cyclosporine or thalidomide. The hives may respond to treatment with PUVA, and the bone pain may respond to bisphosphonates.

Because Schnitzler's syndrome is so rare, the efficacy of different treatments cannot be compared using statistics. Nevertheless, case studies provide evidence that anakinra (otherwise known as kineret) is much more effective for Schnitzler's syndrome than any other drug, and that the improvement in symptoms associated with this treatment is dramatic. For example, Beseda and Nossent (2010) reviewed the literature concerning IL1-RA treatment (i.e. anakinra) for Schnitzler's syndrome. They concluded that, “Twenty-four patients with Schnitzler's syndrome... have been successfully treated with anakinra.” They add that “seven out of seven patients [with Schnitzler’s syndrome], that either interrupted or used anakinra every other day, had relapse of their symptoms within 24-48 h; anakinra was restarted in all patients with the same clinical efficiency.” Kluger et al. (2008) investigated the effectiveness of anakinra for a range of conditions. They searched MEDLINE for English-language trials of anakinra and abstracts from rheumatologial scientific meetings. They conclude that, “Over the last few years it has become increasingly evident that anakinra is highly effective and safe in patients with ... Schnitzler’s syndrome”. The year before, De Koning et al. (2007) reviewed the disease characteristics of Schnitzler syndrome and collected follow-up information to gain insight into long-term prognosis and treatment efficacy. They used data from 94 patients, and their conclusions about treatment for the condition are that, “There have been promising developments in therapeutic options, especially antiinterleukin-1 treatment, which induced complete remission in all 8 patients treated so far.”

Reports of individual patients treated with anakinra illustrate its effectiveness. Beseda and Nossent (ibid.) report treating a longstanding multidrug resistant Schnitzler’s syndrome patient with anakinra: “Within 24 h after the first injection, both the urticaria and the fever disappeared and have not recurred. For the past 6 months, the patient has been in clinical and biochemical remission.” Other authors report “a complete resolution of symptoms” (Dybowski et al., 2008). Crouch et al. (2007) report the effective treatment of a 52-year-old man who had been diagnosed with Schnitzler’s syndrome 8 years earlier: “On review, one week later, the patient’s systemic symptoms had resolved, and his previously elevated white cell count and inflammatory markers had normalised. The use of anakinra in our patient resulted in resolution of symptoms and has enabled cessation of oral prednisolone. Our patient remains symptom free on anakinra after 14 months of follow-up”. Similar stories are reported by Frischmeyer-Guerrerio et al. (2008), Wastiaux et al. (2007), and Eiling et al. (2007), Schneider et al. (2007). De Koning et al. (2006) treated three patients with Schnitzler’s syndrome with thalidomide and anakinra. Thalidomide was only effective for one of the three patients and was discontinued because of polyneuropathy. In contrast, for all three patients, anakinra “led to disappearance of fever and skin lesions within 24 hours. After a follow-up of 16-18 months, all patients are free of symptoms”. The authors concluded that anakinra as a treatment for Schnitzler’s syndrome “is preferable to thalidomide... as it has fewer side effects”.

As well as being more effective, anakinra is safer than the other treatments available for Schnitzler's syndrome. The Cochrane review entitled, ‘Anakinra for rheumatoid arthritis’ (Mertens and Singh, 2009 ) evaluates the (clinical effectiveness and) safety of anakinra in adult patients with rheumatoid arthritis, using data from 2876 patients, from five trials which constituted 781 randomized to placebo and 2065 to anakinra. The authors conclude, “There were no statistically significant differences noted in most safety outcomes with treatment with anakinra versus placebo - including number of withdrawals, deaths, adverse events (total and serious), and infections (total and serious). Injection site reactions were significantly increased, occurring in 1235/1729 (71%) versus 204/729 (28%) of patients treated with anakinra versus placebo, respectively”. These injection site reactions last for no more than four months, and are trivial compared to the very debilitating symptoms of Schnitzler's syndrome.