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.

Supplementary "protein substitute" formulas are typically prescribed for people PKU (starting in infancy) to provide the amino acids and other necessary nutrients that would otherwise be lacking in a low-phenylalanine diet. Tyrosine, which is normally derived from phenylalanine and which is necessary for normal brain function, is usually supplemented. Consumption of the protein substitute formulas can actually reduce phenylalanine levels, probably because it stops the process of protein catabolism from releasing Phe stored in the muscles and other tissues into the blood. Many PKU patients have their highest Phe levels after a period of fasting (such as overnight), because fasting triggers catabolism. A diet that is low in phenylalanine but does not include protein substitutes may also fail to lower blood Phe levels, since a nutritionally insufficient diet may also trigger catabolism. For all these reasons, the prescription formula is an important part of the treatment for patients with classic PKU.

The oral administration of tetrahydrobiopterin (or BH4) (a cofactor for the oxidation of phenylalanine) can reduce blood levels of this amino acid in some people. Most people, however, have little or no benefit.

Tentative evidence supports dietary supplementation with large neutral amino acids (LNAAs). The LNAAs (e.g. leu, tyr, trp, met, his, ile, val, thr) may compete with phe for specific carrier proteins that transport LNAAs across the intestinal mucosa into the blood and across the blood–brain barrier into the brain. It use is really only indicated in adults who will not follow an appropriate diet.

Another interesting treatment strategy for is casein glycomacropeptide (CGMP), which is a milk peptide naturally free of Phe in its pure form CGMP can substitute the main part of the free amino acids in the PKU diet and provides several beneficial nutritional effects compared to free amino acids. The fact that CGMP is a peptide ensures that the absorption rate of its amino acids is prolonged compared to free amino acids and thereby results in improved protein retention and increased satiety compared to free amino acids. Another important benefit of CGMP is that the taste is significantly improved when CGMP substitutes part of the free amino acids and this may help ensure improved compliance to the PKU diet.

Furthermore, CGMP contains a high amount of the phe lowering LNAAs, which constitutes about 41 g per 100 g protein and will therefore help maintain plasma phe levels in the target range.

Treatments for Glycerol Kinase Deficiency are targeted to treat the symptoms because there are no permanent treatments for this disease. The main way to treat these symptoms is by using corticosteroids, glucose infusion, or mineralocorticoids. Corticosteroids are steroid hormones that are naturally produced in the adrenal glands. These hormones regulate stress responses, carbohydrate metabolism, blood electrolyte levels, as well as other uses. The mineralocorticoids, such as aldosterone control many electrolyte levels and allow the kidneys to retain sodium. Glucose infusion is coupled with insulin infusion to monitor blood glucose levels and keep them stable.

Due to the multitude of varying symptoms of this disease, there is no specific treatment that will cure this disease altogether. The symptoms can be treated with many different treatments and combinations of medicines to try to find the correct combination to offset the specific symptoms. Everyone with Glycerol Kinase Deficiency has varying degrees of symptoms and thereby requires different medicines to be used in combination to treat the symptoms; however, this disease is not curable and the symptoms can only be managed, not treated fully.

No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B (also known as pyridoxine). Slightly less than 50% respond to this treatment and need to take supplemental vitamin B for the rest of their lives. Those who do not respond require a Low-sulfur diet (especially monitoring methionine), and most will need treatment with trimethylglycine. A normal dose of folic acid supplement and occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine (so adding cysteine can be important to reduce oxidative stress).

Betaine (N,N,N-trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine, i.e., increasing flux through the re-methylation pathway independent of folate derivatives (which is mainly active in the liver and in the kidneys).The re-formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S-adenosyl-methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS, or cystathione beta synthase deficiency), the plasma methionine level usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromoles/L) may be reached.

Low-protein food is recommended for this disorder, which requires food products low in particular types of amino acids (e.g., methionine).

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).

There is no cure for GALT deficiency, in the most severely affected patients, treatment involves a galactose free diet for life. Early identification and implementation of a modified diet greatly improves the outcome for patients. The extent of residual GALT enzyme activity determines the degree of dietary restriction. Patients with higher levels of residual enzyme activity can typically tolerate higher levels of galactose in their diets. As patients get older, dietary restriction is often relaxed. With the increased identification of patients and their improving outcomes, the management of patients with galactosemia in adulthood is still being understood.

After diagnosis, patients are often supplemented with calcium and vitamin D3. Long-term manifestations of the disease including ovarian failure in females, ataxia. and growth delays are not fully understood. Routine monitoring of patients with GALT deficiency includes determining metabolite levels (galactose 1-phosphate in red blood cells and galactitol in urine) to measure the effectiveness of and adherence to dietary therapy, ophthalmologic examination for the detection of cataracts and assessment of speech, with the possibility of speech therapy if developmental verbal dyspraxia is evident.

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.

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.

Dietary control may help limit progression of the neurological damage.

PKU is not curable. However, if PKU is diagnosed early enough, an affected newborn can grow up with normal brain development by managing and controlling phenylalanine ("Phe") levels through diet, or a combination of diet and medication.

The treatment goal for individuals affected with OTC deficiency is the avoidance of hyperammonemia. This can be accomplished through a strictly controlled low-protein diet, as well as preventative treatment with nitrogen scavenging agents such as sodium benzoate. The goal is to minimize the nitrogen intake while allowing waste nitrogen to be excreted by alternate pathways. Arginine is typically supplemented as well, in an effort to improve the overall function of the urea cycle. If a hyperammonemic episode occurs, the aim of treatment is to reduce the individual's ammonia levels as soon as possible. In extreme cases, this can involve hemodialysis.

Gene therapy had been considered a possibility for curative treatment for OTC deficiency, and clinical trials were taking place at the University of Pennsylvania in the late 1990s. These were halted after the death of Jesse Gelsinger, a young man taking part in a phase I trial using an adenovirus vector. Currently, the only option for curing OTC deficiency is a liver transplant, which restores normal enzyme activity. A 2005 review of 51 patients with OTC deficiency who underwent liver transplant estimated 5-year survival rates of greater than 90%. Severe cases of OTC deficiency are typically evaluated for liver transplant by 6 months of age.

Intake of carbohydrates which must be converted to G6P to be utilized (e.g., galactose and fructose) should be minimized. Although elemental formulas are available for infants, many foods contain fructose or galactose in the forms of sucrose or lactose. Adherence becomes a contentious treatment issue after infancy.

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.

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.

Depending on clinical status and the blood ammonia level, the logical first step is to reduce protein intake and to attempt to maintain energy intake. Initiate intravenous infusion of 10% glucose (or higher, if administered through a central line) and lipids.

Intravenous sodium benzoate and sodium phenylacetate may be helpful. Arginine is usually administered with benzoate and phenylacetate. This is best administered in the setting of a major medical center where facilities for hemodialysis in infants is available.

Glycerol phenylbutyrate is a pre-prodrug that undergoes metabolism to form phenylacetate. Results of a phase 3 study comparing ammonia control in adults showed glycerol phenylbutyrate was noninferior to sodium phenylbutyrate. In a separate study involving young children ages 2 months through 5 years, glycerol phenylbutyrate resulted in a more evenly distributed urinary output of PAGN over 24 hours and accounted for fewer symptoms from accumulation of phenylacetate.

In patients with an extremely high blood ammonia level, rapid treatment with hemodialysis is indicated.

Metabolic disease specialists should provide long-term care with very close and frequent follow-up.

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.

Persistent elevation of uric acid above 6.5 mg/dl warrants treatment with allopurinol to prevent uric acid deposition in kidneys and joints.

Because of the potential for impaired platelet function, coagulation ability should be checked and the metabolic state normalized before surgery. Bleeding time may be normalized with 1–2 days of glucose loading, and improved with ddavp. During surgery, iv fluids should contain 10% dextrose and no lactate.

A patient with GSD, type 1b was treated with a liver transplant at UCSF Medical Center in 1993 that resulted in the resolution of hypoglycemic episodes and the need for the patient to stay away from natural sources of sugar. Other patients have undergone this procedure as well with positive results. Although a liver transplant resulted in the resolution of hypoglycemia it did not however resolve the chronic neutropenia and the risk of infection among patients.

Keeping MSUD under control requires careful monitoring of blood chemistry, both at home and in a hospital setting. DNPH or specialised dipsticks may be used to test the patient's urine for ketones (a sign of metabolic decompensation), when metabolic stress is likely or suspected. Fingerstick tests are performed regularly and sent to a laboratory to determine blood levels of leucine, isoleucine, and valine. Regular metabolic consultations, including blood-draws for full nutritional analysis, are recommended; especially during puberty and periods of rapid growth. MSUD management also involves a specially tailored metabolic formula, a modified diet, and lifestyle precautions such as avoiding fatigue and infections, as well as consuming regular, sufficient calories in proportion to physical stress and exertion. Without sufficient calories, catabolism of muscle protein will result in metabolic crisis. Those with MSUD must be hospitalised for intravenous infusion of sugars and nasogastric drip-feeding of formula, in the event of metabolic decompensation, or anorexia, diarrhea or vomiting. Food avoidance, rejection of formula and picky eating are all common problems with MSUD. Some patients may need to receive all or part of their daily nutrition through a feeding tube.

Since the conversion of dihydroxyphenylserine (Droxidopa; trade name: Northera; also known as L-DOPS, L-threo-dihydroxyphenylserine, L-threo-DOPS and SM-5688), to norepinephrine bypasses the dopamine beta-hydroxylation step of catecholamine synthesis, L-Threo-DOPS is the ideal therapeutic agent. In humans with DβH deficiency, L-Threo-DOPS, a synthetic precursor of noradrenaline, administration has proven effective in dramatic increase of blood pressure and subsequent relief of postural symptoms.

L-DOPS continues to be studied pharmacologically and pharmacokinetically and shows an ability to increase the levels of central nervous system norepinephrine by a significant amount. This is despite the fact that L-DOPS has a relative difficulty crossing the blood-brain barrier when compared to other medications such as L-DOPA. When used concurrently, there is evidence to show that there is increased efficacy as they are both intimately involved and connected to the pathway in becoming norepinephrine.

There is hope and evidence that L-DOPS can be used much more widely to help other conditions or symptoms such as pain, chronic stroke symptoms, and progressive supranuclear palsy, amongst others. Clinically, L-DOPS has been already shown to be helpful in treating a variety of other conditions related to hypotension including the following:

- Diabetes induced orthostatic hypotension

- Dialysis-induced hypotension

- Orthostatic intolerance

- Familial amyloidotic polyneuropathy

- Spinal Cord Injury related hypotension

Empirical evidence of mild effectiveness has been reported using mineralocorticoids or adrenergic receptor agonists as therapies.

Other medications that can bring relief to symptoms include:

- phenylpropanolamine- due to pressor response to vascular α-adrenoceptors

- indomethacin

Vitamin C (ascorbic acid) is also a required cofactor for the Dopamine beta hydroxylase enzyme. Recent research has shown that vitamin C rapidly catalyzes the conversion of dopamine to norepinephrine through stimulation of the dopamine beta hydroxylase enzyme.

Treatment of HFI depends on the stage of the disease, and the severity of the symptoms. Stable patients without acute intoxication events are treated by careful dietary planning that avoids fructose and its metabolic precursors. Fructose is replaced in the diet by glucose, maltose or other sugars. Management of patients with HFI often involves dietitians who have a thorough knowledge of what foods are acceptable.

At this time there is no treatment for transaldolase deficiency.

There is currently research being done to find treatments for transaldolase deficiency. A study done in 2009 used orally administered N-acetylcysteine on transaldolase deficient mice and it prevented the symptoms associated with the disease. N-acetylcysteine is a precursor for reduced glutathione, which is decreased in transaldolase deficient patients.

Initial and general approach for AGL patients are to treat the metabolic complications such as leptin-replacement therapy and/or to control the abnormal levels of lipids or glucose levels. Anti-diabetic medications such as insulin, metformin, or thiazolidinediones are used for insulin-resistance or high glucose levels, or statins or fibrates are used for hyperlipidemia. If symptoms persist, metreleptin can be prescribed.

Metreleptin (MYALEPT) is a recombinant human leptin analog and was approved by FDA in 2014 for generalized lipodystrophy as an adjunct therapy to diet to treat the complication of leptin deficiency. It is the only drug option approved for generalized lipodystrophy-related symptoms and is not intended to use for patients with HIV-related lipodystrophy or complications of partial lipodystrophy. Although it is a recombinant human leptin analog, it is not completely the same as natural leptin as it is produced in "e. coli" and has added methionine residues at is amino terminus. It works by binding to the human leptin receptor, ObR, and activates the receptor. The receptor belongs to the Class I cytokine family and signals the JAK/STAT pathway. It is available as 11.3 mg powder in a vial for subcutaneous injection upon reconstitution and needs to be protected from the light. For treatment, patients and their doctors need to be enrolled and certified in the Myalept Risk Evaluation and Mitigation Strategy (REMS) Program because people on this treatment has a risk of developing anti-metreleptin antibodies that decrease the effectiveness of metreleptin, and increased risk of lymphoma. Clinical study with GL patients who took metreleptin had increased insulin sensitivity, as indicated by decreased HbA1c and fasting glucose level, and reduced caloric intake as well as fasting triglyceride levels.

Plasmapheresis was previously an option for lowering extremely high triglyceride levels for preventing pancreatitis and painful xanthoma, but its use has been decreased after the approval of metreleptin.

Cosmetic treatments, such as facial reconstruction or implants, can be done to replace adipose tissues.

Lifestyle modifications are also recommended, including changes into less fat diet and exercise.

The prognosis of the disease is unknown as of December, 2017.

SR deficiency is currently being treated using a combination therapy of levodopa and carbidopa. These treatments are also used for individuals suffering from Parkinson's. The treatment is noninvasive and only requires the patient to take oral tablets 3 or 4 times a day, where the dosage of levodopa and carbidopa is determined by the severity of the symptoms. Levodopa is in a class of medications called central nervous system agents where its main function is to become dopamine in the brain. Carbidopa is in a class of medications called decarboxylase inhibitors and it works by preventing levodopa from being broken down before it reaches the brain. This treatment is effective in mitigating motor symptoms, but it does not totally eradicate them and it is not as effective on cognitive problems. Patients who have been diagnosed with SR deficiency and have undergone this treatment have shown improvements with most motor impairments including oculogyric crises, dystonia, balance, and coordination.