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.

Whether MTHFR deficiency has any effect at all on all-cause mortality is unclear. One Dutch study showed that the MTHFR mutation was more prevalent in younger individuals (36% relative to 30%), and found that elderly men with MTHFR had an elevated mortality rate, attributable to cancer. Among women, however, no difference in life expectancy was seen. More recently, however, a meta-analysis has shown that overall cancer rates are barely increased with an odds ratio of 1.07, which suggests that an impact on mortality from cancer is small or zero.

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.

The prevalence of 677T homozygozity varies with race. 18-21% of Hispanics and Southern Mediterranean populations have this variant, as do 6-14% of North American Caucasians and <2% of Blacks living outside of Africa.

The prevalence of the 1298C mutation is lower, at 4-12% for most tested populations.

A study in 2000 had identified only 24 cases of severe MTHFR deficiency (from nonsense mutations) across the whole world.

In the world less than 1 in 1.00.000 have HIDS [5]. 200 individuals throughout the world do suffer from MVK.

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.

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.

6-Pyruvoyltetrahydropterin synthase deficiency is an autosomal recessive disorder that causes malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency.

It belongs to the rare diseases. It is a recessive disorder that is accompanied by hyperphenylalaninemia. Commonly reported symptoms are initial truncal hypotonia, subsequent appendicular hypertonia, bradykinesia, cogwheel rigidity, generalized dystonia, and marked diurnal fluctuation. Other reported clinical features include difficulty in swallowing, oculogyric crises, somnolence, irritability, hyperthermia, and seizures. Chorea, athetosis, hypersalivation, rash with eczema, and sudden death have also been reported. Patients with mild phenotypes may deteriorate if given folate antagonists such as methotrexate, which can interfere with a salvage pathway through which dihydrobiopterin is converted into tetrahydrobiopterin via dihydrofolate reductase. Treatment options include substitution with neurotransmitter precursors (levodopa, 5-hydroxytryptophan), monoamine oxidase inhibitors, and tetrahydrobiopterin. Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

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.

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.

Congenital disorder of glycosylation type IIc or Leukocyte adhesion deficiency-2 (LAD2) is a type of leukocyte adhesion deficiency attributable to the absence of neutrophil sialyl-LewisX, a ligand of P- and E-selectin on vascular endothelium. It is associated with "SLC35C1".

This disorder was discovered in two unrelated Israeli boys 3 and 5 years of age, each the offspring of consanguineous parents. Both had severe mental retardation, short stature, a distinctive facial appearance, and the Bombay (hh) blood phenotype, and both were secretor- and Lewis-negative. They both had had recurrent severe bacterial infections similar to those seen in patients with LAD1, including pneumonia, peridontitis, otitis media, and localized cellulitis. Similar to that in patients with LAD1, their infections were accompanied by pronounced leukocytosis (30,000 to 150,000/mm) but an absence of pus formation at sites of recurrent cellulitis. In vitro studies revealed a pronounced defect in neutrophil motility. Because the genes for the red blood cell H antigen and for the secretor status encode for distinct α1,2-fucosyltransferases and the synthesis of Sialyl-LewisX requires an α1,3-fucosyltransferase, it was postulated that a general defect in fucose metabolism is the basis for this disorder. It was subsequently found that GDP-L-fucose transport into Golgi vesicles was specifically impaired, and then missense mutations in the GDP-fucose transporter cDNA of three patients with LAD2 were discovered. Thus, GDP-fucose transporter deficiency is a cause of LAD2.

A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes. They often cause serious, sometimes fatal, malfunction of several different organ systems (especially the nervous system, muscles, and intestines) in affected infants. The most common subtype is CDG-Ia (also referred to as PMM2-CDG) where the genetic defect leads to the loss of phosphomannomutase 2, the enzyme responsible for the conversion of mannose-6-phosphate into mannose-1-phosphate.

No treatment is available for most of these disorders. Mannose supplementation relieves the symptoms in PMI-CDG (CDG-Ib) for the most part, even though the hepatic fibrosis may persist. Fucose supplementation has had a partial effect on some SLC35C1-CDG (CDG-IIc or LAD-II) patients.

A 2009 study reported results from 36 children who had received a stem cell transplant. At the time of follow-up (median time 62 months), 75% of the children were still alive.

The GM1 gangliosidoses (or GM1 gangliosidos"i"s) are caused by a deficiency of beta-galactosidase, with resulting abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells.

GM1 Gangliosidoses are inherited, autosomal recessive sphingolipidoses, resulting from marked deficiency of Acid Beta Galactosidase.

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

I-cell disease is an autosomal recessive disorder caused by a deficiency of GlcNAc phosphotransferase, which phosphorylates mannose residues to mannose-6-phosphate on N-linked glycoproteins in the Golgi apparatus within the cell. Without mannose-6-phosphate to target them to the lysosomes, the enzymes are transported from the Golgi to the extracellular space, resulting in large intracellular inclusions of molecules requiring lysosomal degradation in patients with the disease (hence the name of the disorder). Hydrolases secreted into the blood stream cause little problem as they are deactivated in the neutral pH of the blood.

It can be associated with GNPTA.

In a case report, it was complicated by severe dilative cardiomyopathy(DCM)

Though rare, a deficiency of phosphodiesterase which would cleave GlcNAc from the Mannose 6 Phosphate tag will also cause I-Cell. The presence of lipids, glycosaminoglycans (GAG's) and carbohydrates in the blood provide for the distinguishing characteristic to separate I-Cell from Hurlers Syndrome, in Hurlers, only glycosaminoglycans would be present.

Canine phosphofructokinase deficiency is found mostly in English Springer Spaniels and American Cocker Spaniels, but has also been reported in Whippets and Wachtelhunds. Mixed-breed dogs descended from any of these breeds are also at risk to inherit PFK deficiency.

Inclusion-cell (I-cell) disease, also referred to as mucolipidosis II (ML II), is part of the lysosomal storage disease family and results from a defective phosphotransferase (an enzyme of the Golgi apparatus). This enzyme transfers phosphate to mannose residues on specific proteins. Mannose 6 phosphate serves as a marker for them to be targeted to lysosomes within the cell. Without this marker, the proteins are instead excreted outside the cell—the default pathway for proteins moving through the Golgi apparatus. Lysosomes cannot function without these proteins, which function as catabolic enzymes for the normal breakdown of substances (e.g. oligosaccharides, lipids, and glycosaminoglycans) in various tissues throughout the body (i.e. fibroblasts). As a result, a buildup of these substances occurs within lysosomes because they cannot be degraded, resulting in the characteristic I-cells, or "inclusion cells". These cells can be identified under the microscope. In addition, the defective lysosomal enzymes normally found only within lysosomes are instead found in high concentrations in the blood.

Incidence of Sanfilippo syndrome varies geographically, with approximately 1 case per 280,000 live births in Northern Ireland, 1 per 66,000 in Australia, and 1 per 50,000 in the Netherlands.

The Australian study estimated the following incidences for each subtype of Sanfilippo syndrome:

Glycerol Kinase Deficiency has two main causes associated with it.

- The first cause is isolated enzyme deficiency. The enzyme glycerol kinase is encoded by the X-chromosome in humans. It acts as a catalyst in the phosphorylation of glycerol to glycerol-3-phosphate which plays a key role in formation of triacylglycerol (TAG) and fat storage. There is no genotype–phenotype correlation in isolated GKD and it can be either symptomatic or asymptomatic. Symptomatic means that GKD shows symptoms when it persists in the body and asymptomatic means that the no symptoms appear in the body. In this deficiency the genotype is not associated with the phenotype. The presence of certain mutations in genes has no relation with the phenotype i.e. any resulting physical traits or abnormality.

- The second cause is a deletion or mutation of a single gene. GKD is described by mendelian inheritance and is an X-linked recessive trait due to which it occurs mainly in males and occasionally in females. GKD results when the glycerol kinase gene present on the locus Xp21 of the X chromosome is either deleted or mutated. Females have two X chromosomes and males have one X and one Y chromosome .The expression of recessive genes on the X chromosome is different in males and females. This is due to the fact that genes present on the Y chromosome do not pair up with genes on the X chromosome in males. In females the disorder is expressed only when there are two copies of the affected gene present on each X chromosome but since the glycerol kinase gene is present only on one X chromosome the disorder is not expressed in women. Women have a second good copy that can compensate for the defect on the first copy. On the other hand, males only need a single copy of the recessive gene for the disorder to be expressed. They do not have a second copy that can protect against any defect on the first copy.

Characterised as a recessive disorder, symptomatic presentation requires the inheritance of aldolase A mutations from both parents. This conclusion is substantiated through the continuum type presentation witnessed, wherein heterozygous parents have intermediate enzyme activity. Structural instability has been indicated in four of the patients, with particular sensitivity to increased temperature according to direct enzymatic testing. This is exemplified in the early diagnosis of hereditary pyropoikilocytosis in the Sicilian girl. Deterioration with fever is likewise congruent. However, this direct relation has been disputed due to the increased overall metabolism and oxygen consumption also accompanying such maladies.

Sequence analysis has been conducted for three of the patients each revealing a distinct alteration at regions of typically high conservation. The conversion of the 128th aspartic acid to glycine causes conformational change according to CD spectral analysis and thermal lability in mutagenic analysis. Similarly the charge disruption created through the exchange of the negatively charged glutamic acid for positively charged lysine (at residue 209 of the E helix) disrupts interface interaction of the protein's subunits and therein destabilises its native tetrahedral configuration. The final case is unique in its non-homozygosity. A comparable maternal missense mutation wherein tyrosine is replaced by cysteine alters the carboxy-terminus due to its proximity to a crucial hinge structure. However, the paternal nonsense mutation at arginine 303 truncates the peptide. It is notable that Arg303 is required for enzymatic activity.

The initial 1973 case is atypical, in that no indication of aldolase A structural abnormality was found in isoelectric focusing, heat stabilization, electrophoresis or enzyme kinetics. It was concluded that either disordered regulation or a basic defect creating more rapid tetrameric inactivation were the most probable causes.

Depending on ethnicity and geography, prevalence has been estimated to be between 1 in 40,000 and 1 in 300,000; based on these estimates the disease may be underdiagnosed. Jewish infants of Iraqi or Iranian origin appear to be most at risk based on a study of a community in Los Angeles in which there was a prevalence of 1 in 4200.

On September 1990, the first gene therapy to combat this disease was performed by Dr. William French Anderson on a four-year-old girl, Ashanti DeSilva, at the National Institutes of Health, Bethesda, Maryland, U.S.A.

In April 2016 the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed and recommended for approval a stem cell gene therapy called Strimvelis, for children with ADA-SCID for whom no matching bone marrow donor is available.