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.

A 1999 retrospective study of 74 cases of neonatal onset found that 32 (43%) patients died during their first hyperammonemic episode. Of those who survived, less than 20% survived to age 14. Few of these patients received liver transplants.

Current research suggests that nearly 8% of the population has at least partial DPD deficiency. A diagnostics determination test for DPD deficiency is available and it is expected that with a potential 500,000 people in North America using 5-FU this form of testing will increase. The whole genetic events affecting the DPYD gene and possibly impacting on its function are far from being elucidated, and epigenetic regulations could probably play a major role in DPD deficiency. It seems that the actual incidence of DPD deficiency remains to be understood because it could depend on the very technique used to detect it. Screening for genetic polymorphisms affecting the "DPYD" gene usually identify less than 5% of patients bearing critical mutations, whereas functional studies suggest that up to 20% of patients could actually show various levels of DPD deficiency.

Women could be more at risk than men. It is more common among African-Americans than it is among Caucasians.

Based on the results of worldwide screening of biotinidase deficiency in 1991, the incidence of the disorder is:

5 in 137,401 for profound biotinidase deficiency

- One in 109,921 for partial biotinidase deficiency

- One in 61,067 for the combined incidence of profound and partial biotinidase deficiency

- Carrier frequency in the general population is approximately one in 120.

Raw eggs should be avoided in those with biotin deficiency, because egg whites contain high levels of the anti-nutrient avidin. The name avidin literally means that this protein has an "avidity" (Latin: "to eagerly long for") for biotin. Avidin binds irreversibly to biotin and this compound is then excreted in the urine.

Transaldolase deficiency is recognized as a rare inherited pleiotropic metabolic disorder first recognized and described in 2001 that is autosomal recessive. There have been only a few cases that have been noted, as of 2012 there have been 9 patients recognized with this disease and one fetus.

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.

PNP-deficiency is extremely rare. Only 33 patients with the disorder in the United States have been documented. In the United Kingdom only one child has been diagnosed with this disorder.

Transaldolase deficiency is a disease characterised by abnormally low levels of the Transaldolase enzyme. It is a metabolic enzyme involved in the pentose phosphate pathway. It is caused by mutation in the transaldolase gene (TALDO1). It was first described by Verhoeven et al. in 2001.

This disorder, epidemiologically speaking, is thought to affect approximately 1 in 50,000 newborns according to Jethva, et al. While in the U.S. state of California there seems to be a ratio of 1 in 35,000.

The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one quarter of patients die as a result of thrombotic complications (e.g., heart attack).

Carnosinemia, also called carnosinase deficiency or aminoacyl-histidine dipeptidase deficiency, is a rare autosomal recessive metabolic disorder caused by a deficiency of "carnosinase", a dipeptidase (a type of enzyme that splits dipeptides into their two amino acid constituents).

Carnosine is a dipeptide composed of beta-alanine and histidine, and is found in skeletal muscle and cells of the nervous system. This disorder results in an excess of carnosine in the urine, cerebrospinal fluid (CSF), blood and nervous tissue. Neurological disorders associated with a deficiency of carnosinase, and the resulting carnosinemia ("carnosine in the blood") are common.

A small number of genetic variants have been repeatedly associated with DPD deficiency, such as IVS14+1G>A mutation in intron 14 coupled with exon 14 deletion (a.k.a. DPYD*2A), 496A>G in exon 6; 2846A>T in exon 22 and T1679G (a.k.a. DPYD*13) in exon 13. However, testing patients for these allelic variants usually show high specificity (i.e., bearing the mutation means that severe toxicity will occur indeed)but very low sentivity (i.e., not bearing the mutation does not mean that there is no risk for severe toxicities). Alternatively, phenotyping DPD using ex-vivo enzymatic assay or surrogate testing (i.e., monitoring physiological dihydrouracil to uracil ratio in plasma) has been presented as a possible upfront strategy to detect DPD deficiency. 5-FU test dose (i.e., preliminary administration of a small dose of 5-FU with pharmacokinetics evaluation) has been proposed as another possible alternative strategy to secure the use of fluoropyrimidine drugs.

Malonyl-CoA decarboxylase deficiency (MCD), or Malonic aciduria is an autosomal-recessive metabolic disorder caused by a genetic mutation that disrupts the activity of Malonyl-Coa decarboxylase. This enzyme breaks down Malonyl-CoA (a fatty acid precursor and a fatty acid oxidation blocker) into Acetyl-CoA and carbon dioxide.

Enolase Deficiency is a rare genetic disorder of glucose metabolism. Partial deficiencies have been observed in several caucasian families. The deficiency is transmitted through an autosomal dominant inheritance pattern. The gene for Enolase 1 has been localized to Chromosome 1 in humans. Enolase deficiency, like other glycolytic enzyme deficiences, usually manifests in red blood cells as they rely entirely on anaerobic glycolysis. Enolase deficiency is associated with a spherocytic phenotype and can result in hemolytic anemia, which is responsible for the clinical signs of Enolase deficiency.

Glutathione synthetase deficiency is a rare autosomal recessive metabolic disorder that prevents the production of glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components.

Short-chain acyl-coenzyme A dehydrogenase deficiency (SCADD), also called ACADS deficiency and SCAD deficiency, is an autosomal recessive fatty acid oxidation disorder which affects enzymes required to break down a certain group of fats called short chain fatty acids.

Carnosinase in humans has two forms:

1. Cellular, or tissue carnosinase. This form of the enzyme is found in every bodily tissue. It is a dimer, and hydrolyzes both carnosine and anserine, preferring dipeptides that have a histidine monomer in the c-terminus position. Tissue carnosinase is often considered a "non-specific dipeptidase", based in part on its ability to hydrolyze a range of dipeptide substrates, including those belonging to prolinase.

2. Serum carnosinase. This is the carnosinase found in the blood plasma. Deficiency of this form of carnosinase, along with carnosinuria ("carnosine in the urine"), is the usual metabolic indicator of systemic carnosinase deficiency. Serum carnosinase is a glycoprotein, and splits free carnosine and anserine in the blood. This form of the dipeptidase is not found in human blood until late infancy, slowly rising to adult levels by age 15. Unlike tissue carnosinase, serum carnosinase also hydrolyzes the GABA metabolite homocarnosine. Homocarnosinosis, a neurological disorder resulting in an excess of homocarnosine in the brain, though unaffected by tissue carnosinase, is caused by a deficiency of serum carnosinase in its ability to hydrolyze homocarnosine.

A deficiency of tissue and serum carnosinase, with serum being an indicator, is the underlying metabolic cause of carnosinemia.

There is a deficiency of malate in patients because fumarase enzyme can't convert fumarate into it therefore treatment is with oral malic acid which will allow the krebs cycle to continue, and eventually make ATP.

Without the enzymatic activity of Malonyl-CoA decarboxylase, cellular Mal-CoA increases so dramatically that at the end it is instead broken down by an unspecific short-chain acyl-CoA hydrolase, which produces malonic acid and CoA. Malonic acid is a Krebs cycle inhibitor, preventing the cells to make ATP through oxidation. In this condition, the cells, to make ATP, are forced to increase glycolysis, which produces lactic acid as a by-product. The increase of lactic and malonic acid drastically lowers blood pH, and causes both lactic and malonic aciduria (acidic urine). This condition is very rare, as fewer than 20 cases have been reported.

By 1999, only seven cases of Malonyl- CoA decarboxylase deficiency had been reported in human in Australia; however, this deficiency predominately occurs during childhood. Patients from the seven reported cases of Malonyl- CoA decarboxylase deficiency have an age range between 4 days to 13 years, and they all have the common symptom of delayed neurological development. Similar study was conducted in Netherland, and found seventeen reported cases of Malonyl- CoA decarboxylase deficiency in children age range from 8 days to 12 years.

Although we have not yet gained a clear understanding of the pathogenic mechanism of this deficiency, some researchers have suggested a brain-specific interaction between Malonyl-CoA and CTP1 enzyme which may leads to unexplained symptoms of the MCD deficiency.

Research has found that large amount of MCD are detached in the hypothalamus and cortex of the brain where high levels of lipogenic enzymes are found, indicating that MCD plays a role in lipid synthesis in the brain. Disturbed interaction between Malonyl-CoA and CPT1 may also contributed to abnormal brain development.

Malonyl-CoA decarboxylase plays an important role in the β-oxidation processes in both mitochondria and peroxisome. Some other authors have also hypothesized that it is the MCD deficiency induced inhibition of peroxisomal β-oxidation that contributes to the development delay.

It is caused by the deficiency of the enzyme cystathionine beta synthase, and the deficiency of folic acid, vitamin B12 and pyridoxine (vitamin B6), or mutations of related enzymes.

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.

In the US, the Dietary Reference Intake for adults is 55 µg/day. In the UK it is 75 µg/day for adult males and 60 µg/day for adult females. 55 µg/day recommendation is based on full expression of plasma glutathione peroxidase. Selenoprotein P is a better indicator of selenium nutritional status, and full expression of it would require more than 66 µg/day.

Increased consumption of zinc is another cause of copper deficiency. Zinc is often used for the prevention or treatment of common colds and sinusitis (inflammation of sinuses due to an infection), ulcers, sickle cell disease, celiac disease, memory impairment and acne. Zinc is found in many common vitamin supplements and is also found in denture creams. Recently, several cases of copper deficiency myeloneuropathy were found to be caused by prolonged use of denture creams containing high quantities of zinc.

Metallic zinc is the core of all United States currency coins, including copper coated pennies. People who ingest a large number of coins will have elevated zinc levels, leading to zinc-toxicity-induced copper deficiency and the associated neurological symptoms. This was the case for a 57-year-old woman diagnosed with schizophrenia. The woman consumed over 600 coins, and started to show neurological symptoms such as unsteady gait and mild ataxia.

Carbamoyl phosphate synthetase I deficiency (CPS I deficiency) is an autosomal recessive metabolic disorder that causes ammonia to accumulate in the blood due to a lack of the enzyme carbamoyl phosphate synthetase I. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.