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.

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

The conversion of tryptophan to serotonin and other metabolites depends on vitamin B. If tryptophan catabolism has any impact on brain glutaric acid and other catabolite levels, vitamin B levels should be routinely assayed and normalized in the course of the treatment of GA1.

Symptoms can be reduced through avoidance of leucine, an amino acid. Leucine is a component of most protein-rich foods; therefore, a low-protein diet is recommended. Some isolated cases of this disorder have responded to supplemental biotin; this is not altogether surprising, consider that other biotin-related genetic disorders (such as biotinidase deficiency and holocarboxylase synthetase deficiency) can be treated solely with biotin. Individuals with these multiple carboxylase disorders have the same problem with leucine catabolism as those with 3-methylcrotonyl-CoA carboxylase deficiency.

Dietary control may help limit progression of the neurological damage.

Management for mitochondrial trifunctional protein deficiency entails the following:

- Avoiding factors that might precipitate condition

- Glucose

- Low fat/high carbohydrate nutrition

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.

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.

Although there is currently no cure, treatment includes injections of structurally similar compound, N-Carbamoyl-L-glutamate, an analogue of N-Acetyl Glutamate. This analogue likewise activates CPS1. This treatment mitigates the intensity of the disorder.

If symptoms are detected early enough and the patient is injected with this compound, levels of severe mental retardation can be slightly lessened, but brain damage is irreversible.

Early symptoms include lethargy, vomiting, and deep coma.

The standard treatment is chenodeoxycholic acid (CDCA) replacement therapy. Serum cholesterol levels are also followed. If hypercholesterolemia is not controlled with CDCA, an HMG-CoA reductase inhibitor ("statins" such as simvastatin) can also be used.

Treatment for all forms of this condition primarily relies on a low-protein diet, and depending on what variant of the disorder the individual suffers from, various dietary supplements. All variants respond to the levo isomer of carnitine as the improper breakdown of the affected substances results in sufferers developing a carnitine deficiency. The carnitine also assists in the removal of acyl-CoA, buildup of which is common in low-protein diets by converting it into acyl-carnitine which can be excreted in urine. Though not all forms of methylmalonyl acidemia are responsive to cobalamin, cyanocobalamin supplements are often used in first line treatment for this disorder. If the individual proves responsive to both cobalamin and carnitine supplements, then it may be possible for them to ingest substances that include small amounts of the problematic amino acids isoleucine, threonine, methionine, and valine without causing an attack.

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.

A more extreme treatment includes kidney or liver transplant from a donor without the condition. The foreign organs will produce a functional version of the defective enzymes and digest the methylmalonic acid, however all of the disadvantages of organ transplantation are of course applicable in this situation. There is evidence to suggest that the central nervous system may metabolize methylmalonic-CoA in a system isolated from the rest of the body. If this is the case, transplantation may not reverse the neurological effects of methylmalonic acid previous to the transplant or prevent further damage to the brain by continued build up.

Medications can interfere with folate utilization, including:

- anticonvulsant medications (such as phenytoin, primidone, carbamazepine or valproate )

- metformin (sometimes prescribed to control blood sugar in type 2 diabetes)

- methotrexate, an anti-cancer drug also used to control inflammation associated with Crohn's disease, ulcerative colitis and rheumatoid arthritis.

- sulfasalazine (used to control inflammation associated with Crohn's disease, ulcerative colitis and rheumatoid arthritis)

- triamterene (a diuretic)

- birth control pills

When methotrexate is prescribed, folic acid supplements are sometimes given with the methotrexate. The therapeutic effects of methotrexate are due to its inhibition of dihydrofolate reductase and thereby reduce the rate "de novo" purine and pyrimidine synthesis and cell division. Methotrexate inhibits cell division and is particularly toxic to fast dividing cells, such as rapidly dividing cancer cells and the progenitor cells of the immune system. Folate supplementation is beneficial in patients being treated with long-term, low-dose methotrexate for inflammatory conditions, such as rheumatoid arthritis (RA) or psoriasis, to avoid macrocytic anemia caused by folate deficiency. Folate is often also supplemented before some high dose chemotherapy treatments in an effort to protect healthy tissue. However, it may be counterproductive to take a folic acid supplement with methotrexate in cancer treatment.

Currently, the most common form of treatment for SLOS involves dietary cholesterol supplementation. Anecdotal reports indicate that this has some benefits; it may result in increased growth, lower irritability, improved sociability, less self-injurious behaviour, less tactile defensiveness, fewer infections, more muscle tone, less photosensitivity and fewer autistic behaviours. Cholesterol supplementation begins at a dose of 40–50 mg/kg/day, increasing as needed. It is administered either through consuming foods high in cholesterol (eggs, cream, liver), or as purified food grade cholesterol. Younger children and infants may require tube feeding. However, dietary cholesterol does not reduce the levels of 7DHC, cannot cross the blood–brain barrier, and does not appear to improve developmental outcomes. One empirical study found that cholesterol supplementation did not improve developmental delay, regardless of the age at which it began. This is likely because most developmental delays stem from malformations of the brain, which dietary cholesterol cannot ameliorate due to its inability to cross the blood–brain barrier.

The disorder is treated by strictly reducing the intake of foods rich in plant sterols (e.g., vegetable oils, olives and avocados). However, dietary therapy is often never fully sufficient to control this disease since plant sterols are constituents of all plant-based foods. Statins have been used, and while these lower cholesterol levels and may ameliorate atherosclerotic disease, plant sterol levels are insufficiently lowered by their use alone.

If dietary treatment alone is insufficient, bile acid-binding resins (e.g., cholestyramine, colestipol) could be considered. In October 2002, a new cholesterol absorption inhibitor, ezetimibe, received US Food and Drug Administration (FDA) approval for use in sitosterolemia. This drug is now the standard of care, as it blocks sterol entry and can be used in combination with bile-acid resins.

Finally, ileal bypass has been performed in select cases to decrease the levels of plant sterols in the body, though this therapy was undertaken prior to the advent of ezetimibe.

Since phytanic acid is not produced in the human body, individuals with Refsum disease are commonly placed on a phytanic acid-restricted diet and avoid the consumption of fats from ruminant animals and certain fish, such as tuna, cod, and haddock. Grass feeding animals and their milk are also avoided. Recent research has shown that CYP4 isoform enzymes could help reduce the over-accumulation of phytanic acid "in vivo". Plasmapheresis is another medical intervention used to treat patients. This involves the filtering of blood to ensure there is no accumulation of phytanic acid.

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.

HMG-CoA reductase inhibitors have been examined as treatment for SLOS. Given that this catalyzes the rate-limiting step in cholesterol synthesis, inhibiting it would reduce the buildup of toxic metabolites such as 7DHC. Simvastatin is a known inhibitor of HMG-CoA reductase, and most importantly is able to cross the blood–brain barrier. It has been reported to decrease the levels of 7DHC, as well as increase the levels of cholesterol. The increased cholesterol levels are due to simvastatin's effect on the expression of different genes. Simvastatin increases the expression of "DHCR7", likely leading to increased activity of DHCR7. It has also been shown to increase the expression of other genes involved in cholesterol synthesis and uptake. However, these benefits are dependent on the amount of residual cholesterol synthesis. Because some individuals possess less severe mutations and demonstrate some amount of DCHR7 activity, these people benefit the most from simvastatin therapy as they still have a partially functioning enzyme. For individuals that show no residual DCHR7 activity, such as those homozygous for null alleles or mutations, simvastatin therapy may actually be toxic. This highlights the importance of identifying the specific genotype of the SLOS patient before administering treatment. It is still unknown if simvastatin will improve the behavioural or learning deficits in SLOS.

Since the essential pathology is due to the inability to absorb vitamin B from the bowels, the solution is therefore injection of IV vitamin B. Timing is essential, as some of the side effects of vitamin B deficiency are reversible (such as RBC indices, peripheral RBC smear findings such as hypersegmented neutrophils, or even high levels of methylmalonyl CoA), but some side effects are irreversible as they are of a neurological source (such as tabes dorsalis, and peripheral neuropathy). High suspicion should be exercised when a neonate, or a pediatric patient presents with anemia, proteinuria, sufficient vitamin B dietary intake, and no signs of pernicious anemia.

To treat people with a deficiency of this enzyme, they must avoid needing gluconeogenesis to make glucose. This can be accomplished by not fasting for long periods, and eating high-carbohydrate food. They should avoid fructose containing foods (as well as sucrose which breaks down to fructose).

As with all single-gene metabolic disorders, there is always hope for genetic therapy, inserting a healthy copy of the gene into existing liver cells.

The first suspicion of SPCD in a patient with a non-specific presentation is an extremely low plasma carnitine level. When combined with an increased concentration of carnitine in urine, the suspicion of SPCD can often be confirmed by either molecular testing or functional studies assessing the uptake of carnitine in cultured fibroblasts.

Identification of patients presymptomatically via newborn screening has allowed early intervention and treatment. Treatment for SPCD involves high dose carnitine supplementation, which must be continued for life. Individuals who are identified and treated at birth have very good outcomes, including the prevention of cardiomyopathy. Mothers who are identified after a positive newborn screen but are otherwise asymptomatic are typically offered carnitine supplementation as well. The long-term outcomes for asymptomatic adults with SPCD is not known, but the discovery of mothers with undiagnosed cardiomyopathy and SPCD has raised the possibility that identification and treatment may prevent adult onset manifestations.

In ruminant animals, the gut fermentation of consumed plant materials liberates phytol, a constituent of chlorophyll, which is then converted to phytanic acid and stored in fats. Although humans cannot derive significant amounts of phytanic acid from the consumption of chlorophyll present in plant materials, it has been proposed that the great apes (bonobos, chimpanzees, gorillas, and orangutans) can derive significant amounts of phytanic acid from the hindgut fermentation of plant materials.