A 2011 review of 176 cases found that diagnoses made early in life (within a few days of birth) were associated with more severe disease and a mortality of 33%. Children diagnosed later, and who had milder symptoms, showed a lower mortality rate of ~3%.

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.

That MMA can have disastrous effects on the nervous system has been long reported; however, the mechanism by which this occurs has never been determined. Published on June 15th 2015, research performed on the effects of methylmalonic acid on neurons isolated from fetal rats in an in vitro setting using a control group of neurons treated with an alternate acid of similar pH. These tests have suggested that methylmalonic acid causes decreases in cellular size and increase in the rate of cellular apoptosis in a concentration dependent manner with more extreme effects being seen at higher concentrations. Furthermore, micro-array analysis of these treated neurons have also suggested that on a epigenetic-level methylmalonic acid alters the transcription rate of 564 genes, notably including those involved in the apoptosis, p53, and MAPK signaling pathways.

Isovaleric acidemia is estimated to affect at least 1 in 250,000 births in the United States.

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).

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.

Most individuals with SBCADD are identified through newborn screening, where they present with an elevation of a five carbon acylcarnitine species. Confirmatory testing includes plasma and urine analysis to identify the carnitine and glycine conjugates of 2-methylbutyryl-CoA.

The disorder is caused by a mutation in the "ACADSB" gene, located on the long arm of human chromosome 10 (10q25-q26). It is inherited in an autosomal recessive manner, which means an affected individual must inherit one copy of the mutation from each parent.

D-Bifunctional protein deficiency (officially called 17β-hydroxysteroid dehydrogenase IV deficiency) is an autosomal recessive peroxisomal fatty acid oxidation disorder. Peroxisomal disorders are usually caused by a combination of peroxisomal assembly defects or by deficiencies of specific peroxisomal enzymes. The peroxisome is an organelle in the cell similar to the lysosome that functions to detoxify the cell. Peroxisomes contain many different enzymes, such as catalase, and their main function is to neutralize free radicals and detoxify drugs, such as alcohol. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder, often resembling Zellweger syndrome.

Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment. Other symptoms include severe craniofacial disfiguration, psychomotor delay, and neuronal migration defects. Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life.

Aminoacylase 1 deficiency is a rare inborn error of metabolism. To date only 21 cases have been described.

As of June 2014 (the latest update on HFM in GeneReviews) a total of 32 families had been reported with a clinical diagnosis of HFM of which there was genotypic confirmation in 24 families. Since then, another two confirmed cases have been reported and an additional case was reported based on a clinical diagnosis alone. Most cases emerge from consanguineous parents with homozygous mutations. There are three instances of HFM from non-consanguineous parents in which there were heterozygous mutations. HFM cases are worldwide with mostly private mutations. However, a number of families of Puerto Rican ancestry have been reported with a common pathogenic variant at a splice receptor site resulting in the deletion of exon 3 and the absence of transport function. A subsequent population-based study of newborn infants in Puerto Rico identified the presence of the same variant on the island. Most of the pathogenic variants result in a complete loss of the PCFT protein or point mutations that result in the complete loss of function. However, residual function can be detected with some of the point mutants.

Cerebral creatine deficiencies (CCD's) are a small group of disorders mainly concerned with creatine biosynthesis and utilization in the brain at the blood-brain interface. The most common CCD is:

- creatine transporter defect (CTD), an X-linked condition caused by mutations in the "SLC6A8" gene.

The two other forms of CCD are creatine "enzymatic" defects (CED's) in creatine biosynthesis, i.e. the enzyme deficiencies:

- , and

- guanidinoacetate methyltransferase deficiency.

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.

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.

The inherited forms of methylmalonic acidemia cause defects in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase.

Vitamin B is also needed for the conversion of methylmalonyl-CoA to Succinyl-CoA. Mutations leading to defects in vitamin B metabolism or in its transport frequently result in the development of methylmalonic acidemia.

This disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene—one from each parent—must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

There is a specific pattern of N-acetyl amino acid excretion in the urine. The diagnosis can be confirmed by sequencing of the aminoacylase 1 gene.

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.

ASS1 is the gene mutated in citrullinemia type I. Mutations in this gene have an autosomal recessive mode of inheritance.

People with methylmalonyl CoA mutase deficiency exhibit many symptoms similar to other diseases involving inborn errors of metabolism. Sometimes the symptoms appear shortly after birth, but other times the onset of symptoms is later.

Newborn babies experience with vomiting, acidosis, hyperammonemia, hepatomegaly (enlarged livers), hyperglycinemia (high glycine levels), and hypoglycemia (low blood sugar). Later, cases of thrombocytopenia and neutropenia can occur.

In some cases intellectual and developmental disabilities, such as autism, were noted with increased frequency in populations with methylmalonyl-CoA mutase deficiency.

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.

CTD is caused by mutations in the SLC6A8 gene, located at Xq28. The SLC6A8 gene contains 13 exons and spreads across 8.5 kb of genomic DNA (gDNA). The presence of hemizygous mutations in males and heterozygous mutations in females on the SLC6A8 gene provides evidence that CTD is inherited in an X-linked recessive manner. This usually results in hemizygous males having severe symptoms, while heterozygous female carriers tend to have less severe and more varying symptoms.

Creatine transporter defect (CTD) is an inborn error of creatine metabolism in which creatine is not properly transported to the brain and muscles due to defective creatine transporters. CTD is an X-linked disorder caused by mutations in the SLC6A8 gene. The SLC6A8 gene is located on the short arm of the sex chromosome, Xq28. Hemizygous males with CTD express speech and behavior abnormalities, intellectual disabilities, development delay, seizures, and autistic behavior. Heterozygous females with CTD generally express fewer, less severe symptoms. CTD is one of three different types of cerebral creatine deficiency (CCD). The other two types of CCD are guanidinoacetate methyltransferase (GAMT) deficiency and deficiency. Clinical presentation of CTD is similar to that of GAMT and AGAT deficiency. CTD was first identified in 2001 with the presence of a hemizygous nonsense mutation in the SLC6A8 gene in a male patient.

Delayed growth and development was noted in some patients, although not fully explained, this may be generally associated with the physiological difficulties implicit in errors of energy metabolism. In particular neurological impairment was conjecturally linked with the predominant role of aldolase A in the brain during development. However, this was not substantiated with direct enzymatic kinetic study.

Elevated liver glycogen in one patent was rationalised through an accumulation of fructose-1,6-bisphosphate leading to impaired glucose metabolism and increased diversion of hexose sugars from peripheral tissues. Within the liver the aldolase C isoform is unaffected and therefore hepatic metabolism is assumed to be normally functioning and compensatory processes may be operating.

Compromised immunity has also been indicated, relating to the predominance or exclusivity of aldolase A in leukocytes. This was correlated with recurrent infection in the Sicilian case.

Focal disruption of vital energy metabolism has thus far prevented complete investigation of non-catalytic perturbation. However relation to membrane structural stability has been implicated in the concurrence of aldolase A deficiency and dominant (mild) hereditary elliptocytosis, speculatively also relating to ATP depletion.

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.

Hypermethioninemia is an excess of the amino acid methionine, in the blood. This condition can occur when methionine is not broken down properly in the body.