A 2005 study on rats suggested that hyperprolininemia causes cognitive dysfunction.

Different genetic causes and types of Leigh syndrome have different prognoses, though all are poor. The most severe forms of the disease, caused by a full deficiency in one of the affected proteins, cause death at a few years of age. If the deficiency is not complete, the prognosis is somewhat better and an affected child is expected to survive 6–7 years, and in rare cases, to their teenage years.

Incidence can vary greatly from type-to-type, and from country-to-country.

In Germany, one study reported an incidence of 1.28 per 100,000.

A study in Italy reported an incidence of 0.56 per 100,000.

A study in Norway reported an incidence of 3.9 per 100,000 using the years from 1978 to 1999, with a lower rate in earlier decades.

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

One European study reported a rate of 1 in 254,000; a Japanese study reported a rate of 1 in 357,143. No correlation with other inherited characteristics, or with ethnic origin, is known.

Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. This rare form of the disorder may appear benign at times, but often involves seizures, convulsions, and intellectual disability.

Hyperprolinemia can also occur with other conditions, such as malnutrition or liver disease. In particular, individuals with conditions that cause elevated levels of lactic acid in the blood, such as lactic acidemia, are likely to have elevated proline levels, because lactic acid inhibits the breakdown of proline.

Carnitine palmitoyltransferase II deficiency (CPT-II) is an autosomal recessively inherited genetic metabolic disorder characterized by an enzymatic defect that prevents long-chain fatty acids from being transported into the mitochondria for utilization as an energy source.

The adult myopathic form of this disease was first characterized in 1973 by DiMauro and DiMauro. It is the most common inherited disorder of lipid metabolism affecting the skeletal muscle of adults. CPT II deficiency is also the most frequent cause of hereditary myoglobinuria. Symptoms of this disease are commonly provoked by prolonged exercise or periods without food.

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.

Refsum disease, also known as classic or adult Refsum disease, heredopathia atactica polyneuritiformis, phytanic acid oxidase deficiency and phytanic acid storage disease, is an autosomal recessive neurological disease that results from the over-accumulation of phytanic acid in cells and tissues. It is one of several disorders named after Norwegian neurologist Sigvald Bernhard Refsum (1907–1991). Refsum disease typically is adolescent onset and is diagnosed by above average levels of phytanic acid. Humans obtain the necessary phytanic acid primarily through diet. It is still unclear what function phytanic acid plays physiologically in humans, but has been found to regulate fatty acid metabolism in the liver of mice.

In order to get Tarui’s disease, both parents must be carriers of the genetic defect so that the child is born with the full form of the recessive trait. The best indicator of risk is a family member with PFK deficiency.

Sandhoff disease is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. The disease results from mutations on chromosome 5 in the HEXB gene, critical for the lysosomal enzymes beta-N-acetylhexosaminidase A and B. Sandhoff Disease is clinically indistinguishable from Tay-Sachs Disease. The most common form, infantile Sandhoff disease, is usually fatal by early childhood.

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.

Glycerol Kinase Deficiency (GKD) is an X-linked recessive enzyme defect that is heterozygous in nature. Three clinically distinct forms of this deficiency have been proposed, namely infantile, juvenile, and adult. National Institutes of Health and its Office of Rare Diseases Research (ORDR) branch classifies GKD as a rare disease, known to affect fewer than 200,000 individuals in the United States. The responsible gene lies in a region containing genes in which deletions can cause Duchenne muscular dystrophy and adrenal hypoplasia congenita. Combinations of these three genetic defects including GKD are addressed medically as Complex GKD.

The incidence of metachromatic leukodystrophy is estimated to occur in 1 in 40,000 to 1 in 160,000 individuals worldwide. There is a much higher incidence in certain genetically isolated populations, such as 1 in 75 in Habbanites (a small group of Jews who immigrated to Israel from southern Arabia), 1 in 2,500 in the western portion of the Navajo Nation, and 1 in 8,000 among Arab groups in Israel.

As an autosomal recessive disease, 1 in 40,000 equates to a 1 in 100 carrier frequency in the general population.

There are an estimated 3,600 MLD births per year, with 1,900 alive in the US, 3,100 in Europe, and 49,000 alive worldwide with MLD.

MLD is considered a rare disease in the US and other countries.

MLD has an autosomal recessive inheritance pattern. The inheritance probabilities "per birth" are as follows:

- If both parents are carriers:

- 25% (1 in 4) children will have the disease

- 50% (2 in 4) children will be carriers, but unaffected

- 25% (1 in 4) children will be free of MLD – unaffected child that is not a carrier

- If one parent is affected and one is free of MLD:

- 0% (0) children will have the disorder – only one parent is affected, other parent always gives normal gene

- 100% (4 in 4) children will be carriers (but unaffected)

- If one parent is a carrier and the other is free of MLD:

- 50% (2 in 4) children will be carriers (but unaffected)

- 50% (2 in 4) children will be free of MLD – unaffected child that is not a carrier

In addition to these frequencies there is a 'pseudo'-deficiency that affects 7–15% of the population. People with the pseudo deficiency do not have any MLD problems unless they also have affected status. With the current diagnostic tests, Pseudo-deficiency reports as low enzyme levels but sulfatide is processed normally so MLD symptoms do not exist. This phenomenon wreaks havoc with traditional approaches to Newborn Screening so new screening methods are being developed.

"For further information, see recessive gene and dominance relationship. Also, consult the MLD genetics page at MLD Foundation."

Tay–Sachs disease is a rare autosomal recessive genetic disorder that causes a progressive deterioration of nerve cells and of mental and physical abilities that begins around six months of age and usually results in death by the age of four. It is the most common of the GM2 gangliosidoses. The disease occurs when harmful quantities of cell membrane gangliosides accumulate in the brain's nerve cells, eventually leading to the premature death of the cells.

Infants with Schindler disease tend to die within 4 years of birth, therefore, treatment for this form of the disease is mostly palliative. However, Type II Schindler disease, with its late onset of symptoms, is not characterized by neurological degeneration. There is no known cure for Schindler disease, but bone marrow transplants have been trialed, as they have been successful in curing other glycoprotein disorders.

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.

The disease affects approximately 1 in 140,000 babies and 1 in 60,000 adults a year. It has been reported in almost all ethnic populations.

The prognosis for individuals with Pompe disease varies according to the onset and severity of symptoms. Without treatment the disease is particularly lethal in infants and young children.

Myozyme (alglucosidase alfa) is a recombinant form of the human enzyme acid alpha-glucosidase, and is also currently being used to replace the missing enzyme. In a study which included the largest cohort of patients with Pompe disease treated with enzyme replacement therapy (ERT) to date findings showed that Myozyme treatment clearly prolongs ventilator-free survival and overall survival in patients with infantile-onset Pompe disease as compared to an untreated historical control population. Furthermore, the study demonstrated that initiation of ERT prior to 6 months of age, which could be facilitated by newborn screening, shows great promise to reduce the mortality and disability associated with this devastating disorder. Taiwan and several states in the United States have started the newborn screening and results of such regimen in early diagnosis and early initiation of the therapy have dramatically improved the outcome of the disease; many of these babies have reached the normal motor developmental milestones.

Another factor affecting the treatment response is generation of antibodies against the infused enzyme, which is particularly severe in Pompe infants who have complete deficiency of the acid alpha-glucosidase. Immune tolerance therapy to eliminate these antibodies has improved the treatment outcome.

A Late Onset Treatment Study (LOTS) was published in 2010. The study was undertaken to evaluate the safety and efficacy of aglucosidase alfa in juvenile and adult patients with Pompe disease. LOTS was a randomized, double-blind, placebo-controlled study that enrolled 90 patients at eight primary sites in the United States and Europe. Participants received either aglucosidase alfa or a placebo every other week for 18 months. The average age of study participants was 44 years. The primary efficacy endpoints of the study sought to determine the effect of Myozyme on functional endurance as measured by the six-minute walk test and to determine the effect of aglucosidase alfa on pulmonary function as measured by percent predicted forced vital capacity.

The results showed that, at 78 weeks, patients treated with aglucosidase alfa increased their distance walked in six minutes by an average of approximately 25 meters as compared with the placebo group which declined by 3 meters (P=0.03). The placebo group did not show any improvement from baseline. The average baseline distance walked in six minutes in both groups was approximately 325 meters.

Percent predicted forced vital capacity in the group of patients treated with aglucosidase alfa increased by 1.2 percent at 78 weeks. In contrast, it declined by approximately 2.2 percent in the placebo group (P=0.006).

In infantile Krabbe disease, death usually occurs in early childhood. A 2011 study found 1, 2, 3 year survival rates of 60%, 26%, and 14%, respectively. A few survived for longer and one was still alive at age 13. Patients with late-onset Krabbe disease tend to have a slower progression of the disease and live significantly longer.

The prevalence of Molybdenum co-factor deficiency is estimated as being between 1 in 100 000 and 1 in 200 000. To date more than 100 cases have been reported. However, this may significantly under represent cases.

The symptoms of LSD vary, depending on the particular disorder and other variables such as the age of onset, and can be mild to severe. They can include developmental delay, movement disorders, seizures, dementia, deafness, and/or blindness. Some people with LSDhave enlarged livers (hepatomegaly) and enlarged spleens (splenomegaly), pulmonary and cardiac problems, and bones that grow abnormally.

Menkes disease (MNK), also known as Menkes syndrome, is an X-linked recessive disorder that affects copper levels in the body, leading to copper deficiency.

It is more common in males than females, because it only takes one copy of the X-linked recessive gene to be expressed for a male to develop the disease. In order for females to develop the disorder they would need to express two copies of the gene, one on each X chromosome to develop the disorder. MNK is characterized by kinky hair, growth failure, and deterioration of the nervous system. It is caused by mutations in the copper transport gene, ATP7A, which is responsible for making a protein that is important for regulating the copper levels in the body.

The onset of Menkes disease typically begins during infancy, affecting about 1 in 100,000 to 250,000 newborns. Infants with MNK syndrome often do not live past the age of 3. The disorder was first described by John Hans Menkes in 1962.

Lysosomal storage diseases (LSDs; ) are a group of about 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective, because of a mutation, the large molecules accumulate within the cell, eventually killing it.

Lysosomal storage disorders are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of lipids, glycoproteins (sugar-containing proteins), or so-called mucopolysaccharides. Individually, LSDs occur with incidences of less than 1:100,000; however, as a group, the incidence is about 1:5,000 - 1:10,000. Most of these disorders are autosomal recessively inherited such as Niemann–Pick disease, type C, but a few are X-linked recessively inherited, such as Fabry disease and Hunter syndrome (MPS II).

The lysosome is commonly referred to as the cell's recycling center because it processes unwanted material into substances that the cell can use. Lysosomes break down this unwanted matter by enzymes, highly specialized proteins essential for survival. Lysosomal disorders are usually triggered when a particular enzyme exists in too small an amount or is missing altogether. When this happens, substances accumulate in the cell. In other words, when the lysosome does not function normally, excess products destined for breakdown and recycling are stored in the cell.

Like other genetic disorders, individuals inherit lysosomal storage diseases from their parents. Although each disorder results from different gene mutations that translate into a deficiency in enzyme activity, they all share a common biochemical characteristic – all lysosomal disorders originate from an abnormal accumulation of substances inside the lysosome.

LSDs affect mostly children and they often die at a young and unpredictable age, many within a few months or years of birth. Many other children die of this disease following years of suffering from various symptoms of their particular disorder.