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.

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

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.

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.

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

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.

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.

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.

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.

In ruminant animals, the gut fermentation of consumed plant materials liberates phytol, a constituent of chlorophyll, which is then converted to phytanic acid and stored in fats. Although humans cannot derive significant amounts of phytanic acid from the consumption of chlorophyll present in plant materials, it has been proposed that the great apes (bonobos, chimpanzees, gorillas, and orangutans) can derive significant amounts of phytanic acid from the hindgut fermentation of plant materials.

According to Clinicaltrials.gov, there are no current studies on hyperglycerolemia.

Clinicaltrials.gov is a service of the U.S. National Institutes of Health. Recent research shows patients with high concentrations of blood triglycerides have an increased risk of coronary heart disease. Normally, a blood glycerol test is not ordered. The research was about a child having elevated levels of triglycerides when in fact the child had glycerol kinase deficiency. This condition is known as pseudo-hypertriglyceridemia, a falsely elevated condition of triglycerides. Another group treated patients with elevated concentrations of blood triglycerides with little or no effect on reducing the triglycerides. A few laboratories can test for high concentrations of glycerol, and some laboratories can compare a glycerol-blanked triglycerides assay with the routine non-blanked method. Both cases show how the human body may exhibit features suggestive of a medical disorder when in fact it is another medical condition causing the issue.

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.

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.

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."

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.

A lipid storage disorder (or lipidosis) can be any one of a group of inherited metabolic disorders in which harmful amounts of fats or lipids accumulate in some of the body’s cells and tissues. People with these disorders either do not produce enough of one of the enzymes needed to metabolize and break down lipids or they produce enzymes that do not work properly. Over time, this excessive storage of fats can cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system, liver, spleen and bone marrow.

Inside cells under normal conditions, lysosomes convert, or metabolize, lipids and proteins into smaller components to provide energy for the body.

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.

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.

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.

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.

Many lipid storage disorders can be classified into the subgroup of sphingolipidoses, as they relate to sphingolipid metabolism. Members of this group include Niemann-Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay-Sachs disease, Metachromatic leukodystrophy, multiple sulfatase deficiency and Farber disease. They are generally inherited in an autosomal recessive fashion, but notably Fabry disease is X-linked. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000. Enzyme replacement therapy is available to treat mainly Fabry disease and Gaucher disease, and people with these types of sphingolipidoses may live well into adulthood. The other types are generally fatal by age 1 to 5 years for infantile forms, but progression may be mild for juvenile- or adult-onset forms.

Some of the sphingolipidoses may alternatively be classified into either GM1 gangliosidoses or GM2 gangliosidoses. Tay–Sachs disease belongs to the latter.

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.

Type A Niemann–Pick disease (about 85% of cases) has an extremely poor prognosis, with most cases being fatal by the age of 18 months. Type B (adult onset) and type C (mutation affecting a different molecule) Niemann–Pick diseases have a better prognosis.