There is no proven treatment for congenital lactic acidosis. Treatments that are occasionally used or that are under investigation include the ketogenic diet and dichloroacetate. Other treatments aim to relieve symptoms – for example, anticonvulsants may be used to relieve seizures.

Direct treatment that stimulates the pyruvate dehydrogenase complex (PDC), provides alternative fuels, and prevents acute worsening of the syndrome. However, some correction of acidosis does not reverse all the symptoms. CNS damage is common and limits a full recovery. Ketogenic diets, with high fat and low carbohydrate intake have been used to control or minimize lactic acidosis and anecdotal evidence shows successful control of the disease, slowing progress and often showing rapid improvement. No study has yet been published demonstrating the effectiveness of the ketogenic diet for treatment of PDCD.

There is some evidence that dichloroacetate reduces the inhibitory phosphorylation of pyruvate dehydrogenase complex and thereby activates any residual functioning complex. Resolution of lactic acidosis is observed in patients with E1 alpha enzyme subunit mutations that reduce enzyme stability. However, treatment with dichloroacetate does not improve neurological damage. Oral citrate is often used to treat acidosis.

Nucleoside bypass therapy is an experimental treatment aimed to restore the normal levels of deoxyribonucleotides (dNTPs) in mitochondria.

There is no known curative treatment presently. Hearing aids and cataract surgery may be of use. Control of seizures, heart failure and treatment of infection is important. Tube feeding may be needed.

Succinic acid has been used successfully to treat MELAS syndrome, and also Leighs disease. Patients are managed according to what areas of the body are affected at a particular time. Enzymes, amino acids, antioxidants and vitamins have been used.

Also the following supplements may help:

- CoQ10 has been helpful for some MELAS patients. Nicotinamide has been used because complex l accepts electrons from NADH and ultimately transfers electrons to CoQ10.

- Riboflavin has been reported to improve the function of a patient with complex l deficiency and the 3250T-C mutation.

- The administration of L-arginine during the acute and interictal periods may represent a potential new therapy for this syndrome to reduce brain damage due to impairment of vasodilation in intracerebral arteries due to nitric oxide depletion.

- There is also a case report where succinate was successfully used to treat uncontrolled convulsions in MELAS patients, although this treatment modality is yet to be thoroughly investigated or widely recommended.

In terms of treatment of oculocerebrorenal syndrome for those individuals who are affected by this condition includes the following:

- Glaucoma control (via medication)

- Nasogastric tube feeding

- Physical therapy

- Clomipramine

- Potassium citrate

There are no treatments for MDDS, but some of the symptoms can be managed. For survivors living with MDDS, there are drugs to control epilepsy, and physical therapy can help with muscle control. Liver transplants may benefit people with liver involvement.

The treatment of 2-Hydroxyglutaric aciduria is based on seizure control, the prognosis depends on how severe the condition is.

Treatment for glycogen storage disease type III may involve a high-protein diet, in order to facilitate gluconeogenesis. Additionally the individual may need:

- IV glucose (if oral route is inadvisable)

- Nutritional specialist

- Vitamin D (for osteoporosis/secondary complication)

- Hepatic transplant (if complication occurs)

Patients with propionic acidemia should be started as early as possible on a low protein diet. In addition to a protein mixture that is devoid of methionine, threonine, valine, and isoleucine, the patient should also receive -carnitine treatment and should be given antibiotics 10 days per month in order to remove the intestinal propiogenic flora. The patient should have diet protocols prepared for him with a “well day diet” with low protein content, a “half emergency diet” containing half of the protein requirements, and an “emergency diet” with no protein content. These patients are under the risk of severe hyperammonemia during infections that can lead to comatose states.

Liver transplant is gaining a role in the management of these patients, with small series showing improved quality of life.

In adults, fibrates and statins have been prescribed to treat hyperglycerolemia by lowering blood glycerol levels. Fibrates are a class of drugs that are known as amphipathic carboxylic acids that are often used in combination with Statins. Fibrates work by lowering blood triglyceride concentrations. When combined with statins, the combination will lower LDL cholesterol, lower blood triglycerides and increase HDL cholesterol levels.

If hyperglycerolemia is found in a young child without any family history of this condition, then it may be difficult to know whether the young child has the symptomatic or benign form of the disorder. Common treatments include: a low-fat diet, IV glucose if necessary, monitor for insulin resistance and diabetes, evaluate for Duchenne muscular dystrophy, adrenal insufficiency & developmental delay.

The Genetic and Rare Diseases Information Center (GARD) does not list any treatments at this time.

Usually MSUD patients are monitored by a dietitian. Liver transplantation is another treatment option that can completely and permanently normalise metabolic function, enabling discontinuation of nutritional supplements and strict monitoring of biochemistry and caloric intake, relaxation of MSUD-related lifestyle precautions, and an unrestricted diet. This procedure is most successful when performed at a young age, and weaning from immunosuppressants may even be possible in the long run. However, the surgery is a major undertaking requiring extensive hospitalisation and rigorous adherence to a tapering regime of medications. Following transplant, the risk of periodic rejection will always exist, as will the need for some degree of lifelong monitoring in this respect. Despite normalising clinical presentation, liver transplantation is not considered a cure for MSUD. The patient will still carry two copies of the mutated BKAD gene in each of their own cells, which will consequently still be unable to produce the missing enzyme. They will also still pass one mutated copy of the gene on to each of their biological children. As a major surgery the transplant procedure itself also carries standard risks, although the odds of its success are greatly elevated when the only indication for it is an inborn error of metabolism. In absence of a liver transplant, the MSUD diet must be adhered to strictly and permanently. However, in both treatment scenarios, with proper management, those afflicted are able to live healthy, normal lives without suffering the severe neurological damage associated with the disease.

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.

Management for mitochondrial trifunctional protein deficiency entails the following:

- Avoiding factors that might precipitate condition

- Glucose

- Low fat/high carbohydrate nutrition

A diet with carefully controlled levels of the amino acids leucine, isoleucine, and valine must be maintained at all times in order to prevent neurological damage. Since these three amino acids occur in all natural protein, and most natural foods contain some protein, any food intake must be closely monitored, and day-to-day protein intake calculated on a cumulative basis, to ensure individual tolerance levels are not exceeded at any time. As the MSUD diet is so protein-restricted, and adequate protein is a requirement for all humans, tailored metabolic formula containing all the other essential amino acids, as well as any vitamins, minerals, omega-3 fatty acids and trace elements (which may be lacking due to the limited range of permissible foods), are an essential aspect of MSUD management. These complement the MSUD patient's natural food intake to meet normal nutritional requirements without causing harm. If adequate calories cannot be obtained from natural food without exceeding protein tolerance, specialised low protein products such as starch-based baking mixtures, imitation rice and pasta may be prescribed, often alongside a protein-free carbohydrate powder added to food and/or drink, and increased at times of metabolic stress. Some patients with MSUD may also improve with administration of high doses of thiamine, a cofactor of the enzyme that causes the condition.

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.

The goal for treatment of GSD type 0 is to avoid hypoglycemia. This is accomplished by avoiding fasting by eating every 3-4 hours during the day. At night, uncooked corn starch can be given because it is a complex glucose polymer. This will be acted on slowly by pancreatic amylase and glucose will be absorbed over a 6 hour period.

The primary treatment for type 1 tyrosinemia is nitisinone (Orfadin) and restriction of tyrosine in the diet. Nitisinone inhibits the conversion of 4-OH phenylpyruvate to homogentisic acid by 4-Hydroxyphenylpyruvate dioxygenase, the second step in tyrosine degradation. By inhibiting this enzyme, the accumulation of the fumarylacetoacetate is prevented. Previously, liver transplantation was the primary treatment option and is still used in patients in whom nitisinone fails.

Although no cure currently exists, there is hope in treatment for this class of hereditary diseases with the use of an embryonic mitochondrial transplant.

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.

Treatment consists of oral bicarbonate supplementation. However, this will increase urinary bicarbonate wasting and may well promote a bicarbonate . The amount of bicarbonate given may have to be very large to stay ahead of the urinary losses. Correction with oral bicarbonate may exacerbate urinary potassium losses and precipitate hypokalemia. As with dRTA, reversal of the chronic acidosis should reverse bone demineralization.

Thiazide diuretics can also be used as treatment by making use of contraction alkalosis caused by them.

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).

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.

It is important for MADD patients to maintain strength and fitness without exercising or working to exhaustion. Learning this balance may be more difficult than normally, as muscle pain and fatigue may be perceived differently from normal individuals.

Symptomatic relief from the effects of MADD may sometimes be achieved by administering ribose orally at a dose of approximately 10 grams per 100 pounds (0.2 g/kg) of body weight per day, and exercise modulation as appropriate. Taken hourly, ribose provides a direct but limited source of energy for the cells. Patients with myoadenylate deaminase deficiency do not retain ribose during heavy exercise, so supplementation may be required to rebuild levels of ATP.

Creatine monohydrate could also be helpful for AMPD patients, as it provides an alternative source of energy for anaerobic muscle tissue and was found to be helpful in the treatment of other, unrelated muscular myopathies.

Treatment or management of organic acidemias vary; eg see methylmalonic acidemia, propionic acidemia, isovaleric acidemia, and maple syrup urine disease.

As of 1984 there were no effective treatments for all of the conditions, though treatment for some included a limited protein/high carbohydrate diet, intravenous fluids, amino acid substitution, vitamin supplementation, carnitine, induced anabolism, and in some cases, tube-feeding.

As of 1993 ketothiolase deficiency and other OAs were managed by trying to restore biochemical and physiologic homeostasis; common therapies included restricting diet to avoid the precursor amino acids and use of compounds to either dispose of toxic metabolites or increase enzyme activity.