In terms of treatment for short-chain acyl-CoA dehydrogenase deficiency, some individuals may not need treatment, while others might follow administration of:

- Riboflavin

- Dextrose

- Anticonvulsants

The primary treatment method for fatty-acid metabolism disorders is dietary modification. It is essential that the blood-glucose levels remain at adequate levels to prevent the body from moving fat to the liver for energy. This involves snacking on low-fat, high-carbohydrate nutrients every 2–6 hours. However, some adults and children can sleep for 8–10 hours through the night without snacking.

Carnitor - an L-carnitine supplement that has shown to improve the body's metabolism in individuals with low L-carnitine levels. It is only useful for Specific fatty-acid metabolism disease.

As with most other fatty acid oxidation disorders, individuals with MCADD need to avoid fasting for prolonged periods of time. During illnesses, they require careful management to stave off metabolic decompensation, which can result in death. Supplementation of simple carbohydrates or glucose during illness is key to prevent catabolism. The duration of fasting for individuals with MCADD varies with age, infants typically require frequent feedings or a slow release source of carbohydrates, such as uncooked cornstarch. Illnesses and other stresses can significantly reduce the fasting tolerance of affected individuals.

Individuals with MCADD should have an "emergency letter" that allows medical staff who are unfamiliar with the patient and the condition to administer correct treatment properly in the event of acute decompensation. This letter should outline the steps needed to intervene in a crisis and have contact information for specialists familiar with the individual's care.

Misdiagnosis issues

- The MCADD disorder is commonly mistaken for Reye Syndrome by pediatricians. Reye Syndrome is a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu.

- Most cases of Reye Syndrome are associated with the use of Aspirin during these viral infections.

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.

Treatment consists of dietary protein restriction, particularly leucine. During acute episodes, glycine is sometimes given, which conjugates with isovalerate forming isovalerylglycine, or carnitine which has a similar effect.

Elevated 3-hydroxyisovaleric acid is a clinical biomarker of biotin deficiency. Without biotin, leucine and isoleucine cannot be metabolized normally and results in elevated synthesis of isovaleric acid and consequently 3-hydroxyisovaleric acid, isovalerylglycine, and other isovaleric acid metabolites as well. Elevated serum 3-hydroxyisovaleric acid concentrations can be caused by supplementation with 3-hydroxyisovaleric acid, genetic conditions, or dietary deficiency of biotin. Some patients with isovaleric acidemia may benefit from supplemental biotin. Biotin deficiency on its own can have severe physiological and cognitive consequences that closely resemble symptoms of organic acidemias.

Management for mitochondrial trifunctional protein deficiency entails the following:

- Avoiding factors that might precipitate condition

- Glucose

- Low fat/high carbohydrate nutrition

Other therapeutic interventions include:

- ethosuximide and other anticonvulsant drugs

- GHB receptor antagonist NCS-382

- GABA receptor modulators

- uridine

- acamprosate

- dopaminergic agents

- dextromethorphan

- glutamine

- antioxidants

- Lamotrigine

The GABA(B) receptor antagonist, SGS-742, is currently being tested as a potential therapeutic in an NIH phase II clinical trial (NCT02019667).

Treatment centers on limiting intake of ammonia and increasing its excretion. Dietary protein, a metabolic source of ammonium, is restricted and caloric intake is provided by glucose and fat. Intravenous arginine (argininosuccinase deficiency) sodium phenylbutyrate and sodium benzoate (ornithine transcarbamoylase deficiency) are pharmacologic agents commonly used as adjunctive therapy to treat hyperammonemia in patients with urea cycle enzyme deficiencies. Sodium phenylbutyrate and sodium benzoate can serve as alternatives to urea for the excretion of waste nitrogen. Phenylbutyrate, which is the product of phenylacetate, conjugates with glutamine to form phenylacetylglutamine, which is excreted by the kidneys. Similarly, sodium benzoate reduces ammonia content in the blood by conjugating with glycine to form hippuric acid, which is rapidly excreted by the kidneys. A preparation containing sodium phenylacetate and sodium benzoate is available under the trade name Ammonul.

Acidification of the intestinal lumen using lactulose can decrease ammonia levels by protonating ammonia and trapping it in the stool. This is a treatment for hepatic encephalopathy.

Treatment of severe hyperammonemia (serum ammonia levels greater than 1000 μmol/L) should begin with hemodialysis if it is otherwise medically appropriate and tolerated.

The GABA antagonist CGP-35348 (3-amino-propyl-(diethoxymethyl) phosphinic acid) has been used in Aldh5a1-/- mice with strong results. It has shown to reduce the frequency of absence seizures, though there have been some cases in which it worsened convulsive seizures.

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.

The most important measure is prevention – avoidance of the drugs and foods that cause hemolysis. Vaccination against some common pathogens (e.g. hepatitis A and hepatitis B) may prevent infection-induced attacks.

In the acute phase of hemolysis, blood transfusions might be necessary, or even dialysis in acute kidney failure. Blood transfusion is an important symptomatic measure, as the transfused red cells are generally not G6PD deficient and will live a normal lifespan in the recipient's circulation. Those affected should avoid drugs such as aspirin.

Some patients may benefit from removal of the spleen (splenectomy), as this is an important site of red cell destruction. Folic acid should be used in any disorder featuring a high red cell turnover. Although vitamin E and selenium have antioxidant properties, their use does not decrease the severity of G6PD deficiency.

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.

Treatment of LPI consists of protein-restricted diet and supplementation with oral citrulline. Citrulline is a neutral amino acid that improves the function of the urea cycle and allows sufficient protein intake without hyperammonemia. Under proper dietary control and supplementation, the majority of the LPI patients are able to have a nearly normal life. However, severe complications including pulmonary alveolar proteinosis and renal insufficiency may develop even with proper treatment.

Fertility appears to be normal in women, but mothers with LPI have an increased risk for complications during pregnancy and delivery.

If a metabolic crisis is not treated, a child with VLCADD can develop: breathing problems, seizures, coma, sometimes leading to death.

Treatment involves a diet which includes an adequate amount of riboflavin containing foods. Multi-vitamin and mineral dietary supplements often contain 100% of the Daily Value (1.3 mg) for riboflavin, and can be used by persons concerned about an inadequate diet. Over-the-counter dietary supplements are available in the United States with doses as high as 100 mg, but there is no evidence that these high doses have any additional benefit for healthy people.

Diagnosis of cortisone reductase deficiency is done through analysis of cortisol to cortisone metabolite levels in blood samples. As of now, there is no treatment for cortisone reductase deficiency. Shots of cortisol are quickly metabolised into cortisone by the dysregulated 11β-HSD1 enzyme; however, symptoms can be treated. Treatment of hyperandroginism can be done through prescription of antiandrogens. They do so by inhibiting the release of gonadotropin and luteinizing hormone, both hormones in the pituitary, responsible for the production of testosterone.

In 2009, Monash Children's Hospital at Southern Health in Melbourne, Australia reported that a patient known as Baby Z became the first person to be successfully treated for molybdenum cofactor deficiency type A. The patient was treated with cPMP, a precursor of the molybdenum cofactor. Baby Z will require daily injections of cyclic pyranopterin monophosphate (cPMP) for the rest of her life.

Typically no treatment is needed. If jaundice is significant phenobarbital may be used.

Methemoglobinemia can be treated with supplemental oxygen and methylene blue 1% solution (10 mg/ml) 1 to 2 mg/kg administered intravenously slowly over five minutes. Although the response is usually rapid, the dose may be repeated in one hour if the level of methemoglobin is still high one hour after the initial infusion. Methylene Blue inhibits monoamine oxidase and serotonin toxicity can occur if taken with an SSRI (selective serotonin reuptake inhibitor) medicine.

Methylene blue restores the iron in hemoglobin to its normal (reduced) oxygen-carrying state. This is achieved by providing an artificial electron acceptor (such as methylene blue or flavin) for NADPH methemoglobin reductase (RBCs usually don't have one; the presence of methylene blue allows the enzyme to function at 5× normal levels). The NADPH is generated via the hexose monophosphate shunt.

Genetically induced chronic low-level methemoglobinemia may be treated with oral methylene blue daily. Also, vitamin C can occasionally reduce cyanosis associated with chronic methemoglobinemia but has no role in treatment of acute acquired methemoglobinemia. Diaphorase normally contributes only a small percentage of the red blood cell's reducing capacity, but can be pharmacologically activated by exogenous cofactors (such as methylene blue) to 5 times its normal level of activity.

Diagnosis of canine phosphofructokinase deficiency is similar to the blood tests used in diagnosis of humans. Blood tests measuring the total erythrocyte PFK activity are used for definitive diagnosis in most cases. DNA testing for presence of the condition is also available.

Treatment mostly takes the form of supportive care. Owners are advised to keep their dogs out of stressful or exciting situations, avoid high temperature environments and strenuous exercise. It is also important for the owner to be alert for any signs of a hemolytic episode. Dogs carrying the mutated form of the gene should be removed from the breeding population, in order to reduce incidence of the condition.

The only treatment for classic galactosemia is eliminating lactose and galactose from the diet. Even with an early diagnosis and a restricted diet, however, some individuals with galactosemia experience long-term complications such as speech difficulties, learning disabilities, neurological impairment (e.g. tremors, etc.), and ovarian failure. Symptoms have not been associated with Duarte galactosemia, and many individuals with Duarte galactosemia do not need to restrict their diet at all. However, research corroborates a previously overlooked theory that Duarte galactosemia may lead to language developmental issues in children with no clinical symptoms. Infants with classic galactosemia cannot be breast-fed due to lactose in human breast milk and are usually fed a soy-based formula.

Galactosemia is sometimes confused with lactose intolerance, but galactosemia is a more serious condition. Lactose intolerant individuals have an acquired or inherited shortage of the enzyme lactase, and experience abdominal pains after ingesting dairy products, but no long-term effects. In contrast, a galactosemic individual who consumes galactose can cause permanent damage to their bodies.

Long term complication of galactosemia includes:

- Speech deficits

- Ataxia

- Dysmetria

- Diminished bone density

- Premature ovarian failure

- Cataract

There is no specific treatment beyond maintaining a high fluid intake and avoiding foods that are high in purine.

A diagnosis can be made through a muscle biopsy that shows excess glycogen accumulation. Glycogen deposits in the muscle are a result of the interruption of normal glucose breakdown that regulates the breakdown of glycogen. Blood tests are conducted to measure the activity of phosphofructokinase, which would be lower in a patient with this condition. Patients also commonly display elevated levels of creatine kinase.

Treatment usually entails that the patient refrain from strenuous exercise to prevent muscle pain and cramping. Avoiding carbohydrates is also recommended.

A ketogenic diet also improved the symptoms of an infant with PFK deficiency. The logic behind this treatment is that the low-carb high fat diet forces the body to use fatty acids as a primary energy source instead of glucose. This bypasses the enzymatic defect in glycolysis, lessening the impact of the mutated PFKM enzymes. This has not been widely studied enough to prove if it is a viable treatment, but testing is continuing to explore this option.

Genetic testing to determine whether or not a person is a carrier of the mutated gene is also available.

The treatment of primary immunodeficiencies depends foremost on the nature of the abnormality. Somatic treatment of primarily genetic defects is in its infancy. Most treatment is therefore passive and palliative, and falls into two modalities: managing infections and boosting the immune system.

Reduction of exposure to pathogens may be recommended, and in many situations prophylactic antibiotics or antivirals may be advised.

In the case of humoral immune deficiency, immunoglobulin replacement therapy in the form of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) may be available.

In cases of autoimmune disorders, immunosuppression therapies like corticosteroids may be prescribed.