Treatment of THB deficiencies consists of THB supplementation (2–20 mg/kg per day) or diet to control blood phenylalanine concentration and replacement therapy with neurotransmitters precursors (L-DOPA and 5-HTP) and supplements of folinic acid in DHPR deficiency.

Tetrahydrobiopterin is available as a tablet for oral administration in the form of "tetrahydrobiopterin dihydrochloride" (BH4*2HCL). BH4*2HCL is FDA approved under the trade name Kuvan. The typical cost of treating a patient with Kuvan is $100,000 per year. BioMarin holds the patent for Kuvan until at least 2024, but Par Pharmaceutical has a right to produce a generic version by 2020. BH4*2HCL is indicated at least in tetrahydrobiopterin deficiency caused by GTPCH deficiency or PTPS deficiency.

For women with phenylketonuria, it is important for the health of their children to maintain low Phe levels before and during pregnancy. Though the developing fetus may only be a carrier of the PKU gene, the intrauterine environment can have very high levels of phenylalanine, which can cross the placenta. The child may develop congenital heart disease, growth retardation, microcephaly and intellectual disability as a result. PKU-affected women themselves are not at risk of additional complications during pregnancy.

In most countries, women with PKU who wish to have children are advised to lower their blood Phe levels (typically to between 2 and 6 mg/dL) before they become pregnant, and carefully control their levels throughout the pregnancy. This is achieved by performing regular blood tests and adhering very strictly to a diet, in general monitored on a day-to-day basis by a specialist metabolic dietitian. In many cases, as the fetus' liver begins to develop and produce PAH normally, the mother's blood Phe levels will drop, requiring an increased intake to remain within the safe range of 2–6 mg/dL. The mother's daily Phe intake may double or even triple by the end of the pregnancy, as a result. When maternal blood Phe levels fall below 2 mg/dL, anecdotal reports indicate that the mothers may suffer adverse effects, including headaches, nausea, hair loss, and general malaise. When low phenylalanine levels are maintained for the duration of pregnancy, there are no elevated levels of risk of birth defects compared with a baby born to a non-PKU mother.

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.

This condition is very rare; approximately 600 cases have been reported worldwide. In most parts of the world, only 1% to 2% of all infants with high phenylalanine levels have this disorder. In Taiwan, about 30% of newborns with elevated levels of phenylalanine have a deficiency of THB.

Persons with the genotype for PKU are unaffected in utero, because maternal circulation prevents buildup of [phe]. After birth, PKU in newborns is treated by a special diet with highly restricted phenylalanine content. Persons with genetic predisposition to PKU have normal mental development on this diet. Previously, it was thought safe to withdraw from the diet in the late teens or early twenties, after the central nervous system was fully developed; recent studies suggest some degree of relapse, and a continued phenylalanine-restricted diet is now recommended.

PKU or hyperphenylalaninemia may also occur in persons without the PKU genotype. If the mother has the PKU genotype but has been treated so as to be asymptomatic, high levels of [phe] in the maternal blood circulation may affect the non-PKU fetus during gestation. Mothers successfully treated for PKU are advised to return to the [phe]-restricted diet during pregnancy.

A small subset of patients with hyperphenylalaninemia shows an appropriate reduction in plasma phenylalanine levels with dietary restriction of this amino acid; however, these patients still develop progressive neurologic symptoms and seizures and usually die within the first 2 years of life ("malignant" hyperphenylalaninemia). These infants exhibit normal phenylalanine hydroxylase (PAH) enzymatic activity but have a deficiency in dihydropteridine reductase (DHPR), an enzyme required for the regeneration of tetrahydrobiopterin (THB or BH), a cofactor of PAH.

Less frequently, DHPR activity is normal but a defect in the biosynthesis of THB exists. In either case, dietary therapy corrects the hyperphenylalaninemia. However, THB is also a cofactor for two other hydroxylation reactions required in the syntheses of neurotransmitters in the brain: the hydroxylation of tryptophan to 5-hydroxytryptophan and of tyrosine to L-dopa. It has been suggested that the resulting deficit in the CNS neurotransmitter activity is, at least in part, responsible for the neurologic manifestations and eventual death of these patients.

Carnitine deficiency has been extensively studied, although most commonly as a secondary finding to other metabolic conditions. The first case of SPCD was reported in the 1980s, in a child with fasting hypoketotic hypoglycemia that resolved after treatment with carnitine supplementation. Later cases were reported with cardiomyopathy and muscle weakness. Newborn screening expanded the potential phenotypes associated with SPCD, to include otherwise asymptomatic adults.

Systemic primary carnitine deficiency (SPCD), also known as carnitine uptake defect, carnitine transporter deficiency (CTD) or systemic carnitine deficiency is an inborn error of fatty acid transport caused by a defect in the transporter responsible for moving carnitine across the plasma membrane. Carnitine is an important amino acid for fatty acid metabolism. When carnitine cannot be transported into tissues, fatty acid oxidation is impaired, leading to a variety of symptoms such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. The specific transporter involved with SPCD is OCTN2, coded for by the "SLC22A5" gene located on chromosome 5. SPCD is inherited in an autosomal recessive manner, with mutated alleles coming from both parents.

Acute episodes due to SPCD are often preceded by metabolic stress such as extended fasting, infections or vomiting. Cardiomyopathy can develop in the absence of an acute episode, and can result in death. SPCD leads to increased carnitine excretion in the urine and low levels in plasma. In most locations with expanded newborn screening, SPCD can be identified and treated shortly after birth. Treatment with high doses of carnitine supplementation is effective, but needs to be rigorously maintained for life.

SPCD is more common in the Faroe Islands than in other countries, at least one out of every 1000 inhabitants of the Faroes has the illness, while the numbers for other countries are one in every 100,000. Around 100 persons in the islands have been diagnosed, around one third of the whole population of 48,000 people have been screened for SPCD. Several young Faroese people and children have died a sudden death with cardiac arrest because of SPCD. Scientists believe that around 10% of the Faroese population are carriers of the gene for SPCD. These people are not ill, but may have a lower amount of carnitine in their blood than non-carriers.

GH deficiency is treated by replacing GH with daily injections under the skin or into muscle. Until 1985, growth hormone for treatment was obtained by extraction from human pituitary glands collected at autopsy. Since 1985, recombinant human growth hormone (rHGH) is a recombinant form of human GH produced by genetically engineered bacteria, manufactured by recombinant DNA technology. In both children and adults, costs of treatment in terms of money, effort, and the impact on day-to-day life, are substantial.

GH treatment is not recommended for children who are not growing despite having normal levels of growth hormone, and in the UK it is not licensed for this use. Children requiring treatment usually receive daily injections of growth hormone. Most pediatric endocrinologists monitor growth and adjust dose every 3–6 months and many of these visits involve blood tests and x-rays. Treatment is usually extended as long as the child is growing, and lifelong continuation may be recommended for those most severely deficient. Nearly painless insulin syringes, pen injectors, or a needle-free delivery system reduce the discomfort. Injection sites include the biceps, thigh, buttocks, and stomach. Injection sites should be rotated daily to avoid lipoatrophy. Treatment is expensive, costing as much as US $10,000 to $40,000 a year in the USA.

There is no treatment for MKD. But, the inflammation and the other effects can be reduced to a certain extent.

- IL-1 targeting drugs can be used to reduce the effects of the disorder. Anakinra is antagonist to IL-1 receptors. Anakinra binds the IL-1 receptor, preventing the actions of both IL-1α and IL-1β, and it has been proved to reduce the clinical and biochemical inflammation in MKD. It can effectively decreases the frequency as well as the severity of inflammatory attacks when used on a daily basis. Disadvantages with the usage of this drug are occurrence of painful injection site reaction and as the drug is discontinued in the near future the febrile attacks start. (Examined in a 12-year-old patient).

- Canakinumab is a long acting monoclonal antibody which is directed against IL-1β has shown to be effective in reducing both frequency and severity in patients suffering from mild and severe MKD in case reports and observational case series. It reduces the physiological effects but the biochemical parameter still remain elevated (Galeotti et al. demonstrated that it is more effective than anakinra –considered 6 patients suffering from MKD).

- Anti-TNF therapy might be effective in MKD, but the effect is mostly partial and therapy failure and clinical deterioration have been described frequently in patients on infliximab or etanercept. A beneficial effect of human monoclonal anti-TNFα antibody adalimumab was seen in a small number of MKD patients.

- Most MKD patients are benefited by anti-IL-1 therapy. However, anti-IL-1-resistant disease may also occur. Example. tocilizumab (a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor). This drug is used when the patients are unresponsive towards Anakinra. (Shendi et al. treated a young woman in whom anakinra was ineffective with tocilizumab). It was found that it was effective in reducing the biochemical and clinical inflammation [30].Stoffels et al. observed reduction of frequency and severity of the inflammatory attacks, although after several months of treatment one of these two patients persistently showed mild inflammatory symptoms in the absence of biochemical inflammatory markers.

- A beneficial effect of hematopoietic stem cell transplantation can be used in severe mevalonate kinase deficiency conditions (Improvement of cerebral myelinisation on MRI after allogenic stem cell transplantation was observed in one girl). But, liver transplantation did not influence febrile attacks in this patient.

Hyperphenylalaninemia is a medical condition characterized by mildly or strongly elevated concentrations of the amino acid phenylalanine in the blood. Phenylketonuria (PKU) can result in severe hyperphenylalaninemia. Phenylalanine concentrations ([phe]) are routinely screened in newborns by the neonatal heel prick (Guthrie test), which takes a few drops of blood from the heel of the infant. Standard [phe] concentrations in unaffected persons are about 60µM: [phe] concentrations in persons with untreated phenylketonuria may be many times that (600µM to 2400µM), which indicate that the child is at risk for severe intellectual disability. Phenylketonuria is classed as an autosomal recessive condition: in heterozygous form, [phe] shows a moderate elevation, perhaps two-fold over that of unaffected homozygotes, which is classified as hyperphenylalaninemia ("" + "phenylalanine" + "" = high [phe] in blood).

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.

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.

No curative treatment is available for prolidase deficiency at this time, although palliative treatment is possible to some extent.

The latter mainly focuses on treating the skin lesions through standard methods and stalling collagen degradation (or boosting prolidase performance, where possible), so as to keep the intracellular dipeptide levels low and give the cells time to resynthesise or absorb what proline they cannot recycle so as to be able to rebuild what collagen "does" degrade. Patients can be treated orally with ascorbate (a.k.a. vitamin C, a cofactor of prolyl hydroxylase, an enzyme that hydroxylates proline, increasing collagen stability), manganese (a cofactor of prolidase), suppression of collagenase (a collagen degrading enzyme), and local applications of ointments that contain L-glycine and L-proline. The response to the treatment is inconsistent between affected individuals.

A therapeutic approach based on enzyme replacement (administering functional prolidase) is under consideration.

Due to the weakened immune response in PD cases, it is also of paramount importance to keep any infections under control, often with heavy antibiotics.

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.

Hawkinsinuria, also called 4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency, is an autosomal dominant metabolic disorder affecting the metabolism of tyrosine. Normally, the breakdown of the amino acid tyrosine involves the conversion of 4-hydroxyphenylpyruvate to homogentisate by 4-Hydroxyphenylpyruvate dioxygenase. Complete deficiency of this enzyme would lead to tyrosinemia III. In rare cases, however, the enzyme is still able to produce the reactive intermediate 1,2-epoxyphenyl acetic acid, but is unable to convert this intermediate to homogentisate. The intermediate then spontaneously reacts with glutathione to form 2-L-cystein-S-yl-1,4-dihydroxy-cyclohex-5-en-1-yl acetic acid (hawkinsin).

Patients present with metabolic acidosis during the first year of life, which should be treated by a phenylalanine- and tyrosine-restricted diet. The tolerance toward these amino acids normalizes as the patients get older. Then only a chlorine-like smell of the urine indicates the presence of the condition, patients have a normal life and do not require treatment or a special diet.

The production of hawkinsin is the result of a gain-of-function mutation, inheritance of hawkinsinuria is therefore autosomal dominant (presence of a single mutated copy of the gene causes the condition). Most other inborn errors of metabolism are caused by loss-of-function mutations, and hence have recessive inheritance (condition occurs only if both copies are mutated).

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)

Mevalonate kinase deficiency, also called mevalonic aciduria and hyper immunoglobin D syndrome is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids.

It is characterized by an elevated level of immunoglobin D in the blood.

The enzyme is involved in biosynthesis of cholesterols and isoprenoids. The enzyme is necessary for the conversion of mevalonate to mevalonate-5-phosphate in the presence of Mg2+ [Harper’s biochemistry manual]. Mevalonate kinase deficiency causes the accumulation of mevalonate in urine and hence the activity of the enzyme is again reduced Mevalonate kinase deficiency. It was first described as HIDS in 1984.

Treatment consists of maintaining normal levels of calcium, phosphorus, and Vitamin D. Phosphate binders, supplementary Calcium and Vitamin D will be used as required.

Saccharopinuria (an excess of saccharopine in the urine), also called saccharopinemia, saccharopine dehydrogenase deficiency or alpha-aminoadipic semialdehyde synthase deficiency, is a variant form of hyperlysinemia. It is caused by a partial deficiency of the enzyme saccharopine dehydrogenase, which plays a secondary role in the lysine metabolic pathway. Inheritance is thought to be autosomal recessive, but this cannot be established as individuals affected by saccharopinuria typically have only a 40% reduction in functional enzyme.

There is no cure for congenital alpha-mannosidosis. Treatment is limited to reducing or controlling the symptoms of this disorder by, for example, taking medication to control seizures, using a hearing aid to assist with hearing loss, and by having routine physical therapy to assist with muscular pain and weakness. In some cases, a wheelchair is recommended if muscle or spinal impairments immobilize the individual affected. Despite early reports to the contrary, bone marrow transplants performed at an early age have shown promise in halting the progression of this disorder.

The life expectancy in alpha-mannosidosis is highly variable. Individuals with early onset severe disease often do not survive beyond childhood, whereas those with milder disorders may survive well into adult life.

An inborn error of steroid metabolism is an inborn error of metabolism due to defects in steroid metabolism.

A variety of conditions of abnormal steroidogenesis exist due to genetic mutations in the steroidogenic enzymes involved in the process, of which include:

- 18,20-Desmolase (P450scc) deficiency: blocks production of all steroid hormones from cholesterol

- 3β-Hydroxysteroid dehydrogenase type 2 deficiency: impairs progestogen and androgen metabolism; prevents the synthesis of estrogens, glucocorticoids, and mineralocorticoids; causes androgen deficiency in males and androgen excess in females

- Combined 17α-hydroxylase/17,20-lyase deficiency: impairs progestogen metabolism; prevents androgen, estrogen, and glucocorticoid synthesis; causes mineralocorticoid excess

- Isolated 17,20-lyase deficiency: prevents androgen and estrogen synthesis

- 21-Hydroxylase deficiency: prevents glucocorticoid and mineralocorticoid synthesis; causes androgen excess in females

- 11β-Hydroxylase type 1 deficiency: impairs glucocorticoid and mineralocorticoid metabolism; causes glucocorticoid deficiency and mineralocorticoid excess as well as androgen excess in females

- 11β-Hydroxylase type 2 deficiency: impairs corticosteroid metabolism; results in excessive mineralocorticoid activity

- 18-Hydroxylase deficiency: impairs mineralocorticoid metabolism; results in mineralocorticoid deficiency

- 18-Hydroxylase overactivity: impairs mineralocorticoid metabolism; results in mineralocorticoid excess

- 17β-Hydroxysteroid dehydrogenase deficiency: impairs androgen and estrogen metabolism; results in androgen deficiency in males and androgen excess and estrogen deficiency in females

- 5α-Reductase type 2 deficiency: prevents the conversion of testosterone to dihydrotestosterone; causes androgen deficiency in males

- Aromatase deficiency: prevents estrogen synthesis; causes androgen excess in females

- Aromatase excess: causes excessive conversion of androgens to estrogens; results in estrogen excess in both sexes and androgen deficiency in males

In addition, several conditions of abnormal steroidogenesis due to genetic mutations in "receptors", as opposed to enzymes, also exist, including:

- Gonadotropin-releasing hormone (GnRH) insensitivity: prevents synthesis of sex steroids by the gonads in both sexes

- Follicle-stimulating (FSH) hormone insensitivity: prevents synthesis of sex steroids by the gonads in females; merely causes problems with fertility in males

- Luteinizing hormone (LH) insensitivity: prevents synthesis of sex steroids by the gonads in males; merely causes problems with fertility in females

- Luteinizing hormone (LH) oversensitivity: causes androgen excess in males, resulting in precocious puberty; females are asymptomatic

No activating mutations of the GnRH receptor in humans have been described in the medical literature, and only one of the FSH receptor has been described, which presented as asymptomatic.

Treatment: There is no treatment or way to reverse the disease. Treatment will focus on the symptoms an individual has, such as seizure medication.

- It is possible that if an individual receives a bone marrow transplant, they could receive healthy bone marrow cells which would produce normal amounts of fucosidase. But there not is enough research to prove this is an effective treatment.

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

An example is lactose intolerance.

Carbohydrates account for a major portion of the human diet. These carbohydrates are composed of three principal monosaccharides: glucose, fructose and galactose; in addition glycogen is the storage form of carbohydrates in humans. The failure to effectively use these molecules accounts for the majority of the inborn errors of human carbohydrates metabolism.