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.

Infant mortality is high for patients diagnosed with early onset; mortality can occur within less than 2 months, while children diagnosed with late-onset syndrome seem to have higher rates of survival. Patients suffering from a complete lesion of mut0 have not only the poorest outcome of those suffering from methylaonyl-CoA mutase deficiency, but also of all individuals suffering from any form of methylmalonic acidemia.

No sexual predilection is observed because the deficiency of glycogen synthetase activity is inherited as an autosomal recessive trait.

The overall frequency of glycogen-storage disease is approximately 1 case per 20,000–25,000 people. Glycogen-storage disease type 0 is a rare form, representing less than 1% of all cases. The identification of asymptomatic and oligosymptomatic siblings in several glycogen-storage disease type 0 families has suggested that glycogen-storage disease type 0 is underdiagnosed.

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.

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).

Depending on clinical status and the blood ammonia level, the logical first step is to reduce protein intake and to attempt to maintain energy intake. Initiate intravenous infusion of 10% glucose (or higher, if administered through a central line) and lipids.

Intravenous sodium benzoate and sodium phenylacetate may be helpful. Arginine is usually administered with benzoate and phenylacetate. This is best administered in the setting of a major medical center where facilities for hemodialysis in infants is available.

Glycerol phenylbutyrate is a pre-prodrug that undergoes metabolism to form phenylacetate. Results of a phase 3 study comparing ammonia control in adults showed glycerol phenylbutyrate was noninferior to sodium phenylbutyrate. In a separate study involving young children ages 2 months through 5 years, glycerol phenylbutyrate resulted in a more evenly distributed urinary output of PAGN over 24 hours and accounted for fewer symptoms from accumulation of phenylacetate.

In patients with an extremely high blood ammonia level, rapid treatment with hemodialysis is indicated.

Metabolic disease specialists should provide long-term care with very close and frequent follow-up.

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.

Overall, according to a study in British Columbia, approximately 2.3 children per 100,000 births (1 in 43,000) have some form of glycogen storage disease. In the United States, they are estimated to occur in 1 per 20,000–25,000 births. Dutch incidence rate is estimated to be 1 per 40,000 births.

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.

Glycerol Kinase Deficiency causes the condition known as hyperglycerolemia, an accumulation of glycerol in the blood and urine. This excess of glycerol in bodily fluids can lead to many more potentially dangerous symptoms. Common symptoms include vomiting and lethargy. These tend to be the only symptoms, if any, present in adult GKD which has been found to present with fewer symptoms than infant or juvenile GKD. When GKD is accompanied by Duchenne Muscular Dystrophy and Adrenal Hypoplasia Congenita, also caused by mutations on the Xp21 chromosome, the symptoms can become much more severe. Symptoms visible at or shortly after birth include:

- cryptorchidism

- strabismus

- seizures

Some other symptoms that become more noticeable with time would be:

- metabolic acidosis

- hypoglycemia

- adrenal cortex insufficiency

- learning disabilities

- osteoporosis

- myopathy

Many of the physically visible symptoms, such as cryptorchidism, strabismus, learning disabilities, and myopathy, tend to have an added psychological effect on the subject due to the fact that they can set him or her apart from those without GKD. Cryptorchidism, the failure of one or both of the testes to descend to the scrotum, has been known to lead to sexual identity confusion amongst young boys because it is such a major physiological anomaly. Strabismus is the misalignment of one’s eyes. Typically, one is focused but the other is “lazy” and is directed inward or out ward (up and down is less common but does occur).

Citrullinemia type I (CTLN1), also known as arginosuccinate synthetase deficiency, is a rare disease caused by a deficiency in argininosuccinate synthetase, an enzyme involved in excreting excess nitrogen from the body. There are mild and severe forms of the disease, which is one of the urea cycle disorders.

The main treatments for CTLN1 include a low-protein, high-calorie diet with amino acid supplements, particularly arginine. The Ucyclyd protocol, using buphenyl and ammonul, is used for treatment as well. Hyperammonemia is treated with hemodialysis; intravenous arginine, sodium benzoate, and sodium phenylacetate. In some cases, liver transplantation may be a viable treatment. L-carnitine is used in some treatment protocols.

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 addition to the characteristic excessive orotic acid in the urine, patients typically have megaloblastic anemia (UMP synthase deficiency) which cannot be cured by administration of vitamin B12 or folic acid.

It also can cause inhibition of RNA and DNA synthesis and failure to thrive.

Orotic aciduria is a disease yielding an excessive excretion of orotic acid in urine. It causes a characteristic form of anemia and may be associated with mental and physical retardation.

Orotic acid is an intermediate product in pyrimidine synthesis pathway, a subsequent product of which plays a role in conversion between dihydrofolate and tetrahydrofolate. Orotic aciduria is associated with megaloblastic anemia due to decreased pyrimidine synthesis, which leads to decreased nucleotide-lipid cofactors needed for erythrocyte membrane synthesis in the bone marrow.

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.

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 human GALK1 gene contains 8 exons and spans approximately 7.3 kb of genomic DNA. The GALK1 promoter was found to have many features in common with other housekeeping genes, including high GC content, several copies of the binding site for the Sp1 transcription factor and the absence of TATA-box and CCAAT-box motifs typically present in eukaryotic polymerase II promoters. Analysis by 5-prime-RACE PCR indicated that the GALK1 mRNA is heterogeneous at the 5-prime end, with transcription sites occurring at many locations between 21 and 61 bp upstream of the ATG start site of the coding region. In vitro translation experiments of the GALK1 cDNA indicated that the protein is cytosolic and not associated with endoplasmic reticulum membrane.

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.

N-Acetylglutamate synthase (or synthetase) deficiency is an autosomal recessive urea cycle disorder.

The following list includes such examples:

- - hyperammonemia due to ornithine transcarbamylase deficiency

- - hyperinsulinism-hyperammonemia syndrome (glutamate dehydrogenase 1)

- - hyperornithinemia-hyperammonemia-homocitrullinuria

- - hyperammonemia due to N-acetylglutamate synthetase deficiency

- - hyperammonemia due to carbamoyl phosphate synthetase I deficiency (carbamoyl phosphate synthetase I)

- - hyperlysinuria with hyperammonemia (genetics unknown)

- Methylmalonic acidemia

- Isovaleric acidemia

- Propionic acidemia

- Carnitine palmitoyltransferase II deficiency

- Transient hyperammonemia of the newborn, specifically in the preterm

Galactose epimerase deficiency, also known as GALE deficiency, Galactosemia III and UDP-galactose-4-epimerase deficiency, is a rare, autosomal recessive form of galactosemia associated with a deficiency of the enzyme "galactose epimerase".

Treatment centers on limiting intake of ammonia and increasing its excretion. Dietary protein, a metabolic source of ammonium, is restricted and caloric intake is provided by glucose and fat. Intravenous arginine (argininosuccinase deficiency) sodium phenylbutyrate and sodium benzoate (ornithine transcarbamoylase deficiency) are pharmacologic agents commonly used as adjunctive therapy to treat hyperammonemia in patients with urea cycle enzyme deficiencies. Sodium phenylbutyrate and sodium benzoate can serve as alternatives to urea for the excretion of waste nitrogen. Phenylbutyrate, which is the product of phenylacetate, conjugates with glutamine to form phenylacetylglutamine, which is excreted by the kidneys. Similarly, sodium benzoate reduces ammonia content in the blood by conjugating with glycine to form hippuric acid, which is rapidly excreted by the kidneys. A preparation containing sodium phenylacetate and sodium benzoate is available under the trade name Ammonul.

Acidification of the intestinal lumen using lactulose can decrease ammonia levels by protonating ammonia and trapping it in the stool. This is a treatment for hepatic encephalopathy.

Treatment of severe hyperammonemia (serum ammonia levels greater than 1000 μmol/L) should begin with hemodialysis if it is otherwise medically appropriate and tolerated.

Essential fructosuria is a genetic condition that is inherited in an autosomal recessive manner. Mutations in the "KHK" gene, located on chromosome 2p23.3-23.2 are responsible. The incidence of essential fructosuria has been estimated at 1:130,000. The actual incidence is likely higher, because those affected are asymptomatic.