Short-chain acyl-coenzyme A dehydrogenase deficiency affected infants will have vomiting, low blood sugar, a lack of energy (lethargy), poor feeding, and failure to gain weight and grow. Additional features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delays, and microcephaly. The symptoms of short-chain acyl-CoA dehydrogenase deficiency may be triggered during illnesses such as viral infections. In some cases, signs and symptoms may not appear until adulthood, when some individuals may develop muscle weakness, while other individuals mild symptoms may never be diagnosed.

Typically, initial signs and symptoms of this disorder occur during infancy and include low blood sugar (hypoglycemia), lack of energy (lethargy), and muscle weakness. There is also a high risk of complications such as liver abnormalities and life-threatening heart problems. Symptoms that begin later in childhood, adolescence, or adulthood tend to be milder and usually do not involve heart problems. Episodes of very long-chain acyl-coenzyme A dehydrogenase deficiency can be triggered by periods of fasting, illness, and exercise.

It is common for babies and children with the early and childhood types of VLCADD to have episodes of illness called metabolic crises. Some of the first symptoms of a metabolic crisis are: extreme sleepiness, behavior changes, irritable mood, poor appetite.

Some of these other symptoms of VLCADD in infants may also follow: fever, nausea, diarrhea, vomiting, hypoglycemia.

Typically, initial signs and symptoms of this disorder occur during infancy or early childhood and can include feeding difficulties, lethargy, hypoglycemia, hypotonia, liver problems, and abnormalities in the retina. Muscle pain, a breakdown of muscle tissue, and abnormalities in the nervous system that affect arms and legs (peripheral neuropathy) may occur later in childhood. There is also a risk for complications such as life-threatening heart and breathing problems, coma, and sudden unexpected death. Episodes of LCHAD deficiency can be triggered by periods of fasting or by illnesses such as viral infections.

Depending on the affected gene(s), this disorder may present symptoms that range from mild to life-threatening.

- Stroke

- Progressive encephalopathy

- Seizure

- Kidney failure

- Vomiting

- Dehydration

- Failure to thrive and developmental delays

- Lethargy

- Repeated Yeast infections

- Acidosis

- Hepatomegaly

- Hypotonia

- Pancreatitis

- Respiratory distress

Short-chain acyl-coenzyme A dehydrogenase deficiency (SCADD), also called ACADS deficiency and SCAD deficiency, is an autosomal recessive fatty acid oxidation disorder which affects enzymes required to break down a certain group of fats called short chain fatty acids.

Babies with this disorder are usually healthy at birth. The signs and symptoms may not appear until later in infancy or childhood and can include poor feeding and growth (failure to thrive), a weakened and enlarged heart (dilated cardiomyopathy), seizures, and low numbers of red blood cells (anemia). Another feature of this disorder may be very low blood levels of carnitine (a natural substance that helps convert certain foods into energy).

Isobutyryl-CoA dehydrogenase deficiency may be worsened by long periods without food (fasting) or infections that increase the body's demand for energy. Some individuals with gene mutations that can cause isobutyryl-CoA dehydrogenase deficiency may never experience any signs and symptoms of the disorder.

Typically, initial signs and symptoms of this disorder occur during infancy or early childhood and can include poor appetite, vomiting, diarrhea, lethargy, hypoglycemia, hypotonia, liver problems, and abnormally high levels of hyperinsulinism. Insulin controls the amount of sugar that moves from the blood into cells for conversion to energy. Individuals with 3-hydroxyacyl-coenzyme A dehydrogenase deficiency are also at risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden unexpected death.

Problems related to 3-hydroxyacyl-coenzyme A dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

If a metabolic crisis is not treated, a child with VLCADD can develop: breathing problems, seizures, coma, sometimes leading to death.

Methylmalonic acidemia (MMA), also called methylmalonic aciduria, is an autosomal recessive metabolic disorder. It is a classical type of organic acidemia. The result of this condition is the inability to properly digest specific fats and proteins, which in turn leads to a buildup of a toxic level of methylmalonic acid in the blood.

Methylmalonic acidemia stems from several genotypes, all forms of the disorder usually diagnosed in the early neonatal period, presenting progressive encephalopathy, and secondary hyperammonemia. The disorder can result in death if undiagnosed or left untreated. It is estimated that this disorder has a frequency of 1 in 48,000 births, though the high mortality rate in diagnosed cases make exact determination difficult. Methylmalonic acidemias are found with an equal frequency across ethnic boundaries.

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.

Signs and symptoms of this disorder include low levels of ketones (products of fat breakdown that are used for energy) and low blood sugar (hypoglycemia). Together these signs are called hypoketotic hypoglycemia. People with this disorder typically also have an enlarged liver (hepatomegaly), muscle weakness, and elevated levels of carnitine in the blood.

A 2001 study followed up on 50 patients. Of these 38% died in childhood while the rest suffered from problems with morbidity.

Coenzyme Q10 deficiency is a deficiency of Coenzyme Q10.

It can be associated with "COQ2", "APTX", "PDSS2", "PDSS1", "CABC1", and "COQ9".

Some forms may be more treatable than other mitochondrial diseases.

Isobutyryl-coenzyme A dehydrogenase deficiency, commonly known as IBD deficiency, is a rare metabolic disorder in which the body is unable to process certain amino acids properly.

People with this disorder have inadequate levels of an enzyme that helps break down the amino acid valine, resulting in a buildup of valine in the urine, a symptom called valinuria.

The symptoms of Leigh syndrome are classically described as beginning in infancy and leading to death within a span of several years; however, as more cases are recognized, it is apparent that symptoms can emerge at any age—including adolescence or adulthood—and patients can survive for many years following diagnosis. Symptoms are often first seen after a triggering event that taxes the body's energy production, such as an infection or surgery. The general course of Leigh syndrome is one of episodic developmental regression during times of metabolic stress. Some patients have long periods without disease progression while others develop progressive decline.

Infants with the syndrome have symptoms that include diarrhea, vomiting, and dysphagia (trouble swallowing or sucking), leading to a failure to thrive. Children with early Leigh disease also may appear irritable and cry much more than usual. Seizures are often seen. Excess lactate may be seen in the urine, cerebrospinal fluid, and blood of a person with Leigh syndrome.

As the disease progresses, the muscular system is debilitated throughout the body, as the brain cannot control the contraction of muscles. Hypotonia (low muscle tone and strength), dystonia (involuntary, sustained muscle contraction), and ataxia (lack of control over movement) are often seen in people with Leigh disease. The eyes are particularly affected; the muscles that control the eyes become weak, paralyzed, or uncontrollable in conditions called ophthalmoparesis (weakness or paralysis) and nystagmus (involuntary eye movements). Slow saccades are also sometimes seen. The heart and lungs can also fail as a result of Leigh disease. Hypertrophic cardiomyopathy (thickening of part of the heart muscle) is also sometimes found and can cause death; asymmetric septal hypertrophy has also been associated with Leigh syndrome. In children with Leigh-syndrome associated ventricular septal defects, caused by pyruvate dehydrogenase deficiency, high forehead and large ears are seen; facial abnormalities are not typical of Leigh syndrome.

However, respiratory failure is the most common cause of death in people with Leigh syndrome. Other neurological symptoms include peripheral neuropathy, loss of sensation in extremities caused by damage to the peripheral nervous system.

Hypertrichosis is seen in Leigh syndrome caused by mutations in the nuclear gene SURF1.

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.

3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADH deficiency) is a rare condition that prevents the body from converting certain fats to energy, particularly during fasting. Normally, through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to metabolize fats and convert them to energy. People with 3-hydroxyacyl-coenzyme A dehydrogenase deficiency have inadequate levels of an enzyme required for a step that metabolizes groups of fats called medium chain fatty acids and short chain fatty acids; for this reason this disorder is sometimes called medium- and short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (M/SCHAD) deficiency.

Urocanic aciduria is thought to be relatively benign. Although aggressive behavior and mental retardation have been reported with the disorder, no definitive neurometabolic connection has yet been established.

2,4 Dienoyl-CoA reductase deficiency is an inborn error of metabolism resulting in defective fatty acid oxidation caused by a deficiency of the enzyme 2,4 Dienoyl-CoA reductase. Lysine degradation is also affected in this disorder leading to hyperlysinemia. The disorder is inherited in an autosomal recessive manner, meaning an individual must inherit mutations in "NADK2," located at 5p13.2 from both of their parents. NADK2 encodes the mitochondrial NAD kinase. A defect in this enzyme leads to deficient mitochondrial nicotinamide adenine dinucleotide phosphate levels. 2,4 Dienoyl-CoA reductase, but also lysine degradation are performed by NADP-dependent oxidoreductases explaining how NADK2 deficiency can lead to multiple enzyme defects.

2,4-Dienoyl-CoA reductase deficiency was initially described in 1990 based on a single case of a black female who presented with persistent hypotonia. Laboratory investigations revealed elevated lysine, low levels of carnitine and an abnormal acylcarnitine profile in urine and blood. The abnormal acylcarnitine species was eventually identified as 2-trans,4-cis-decadienoylcarnitine, an intermediate of linoleic acid metabolism. The index case died of respiratory failure at four months of age. Postmortem enzyme analysis on liver and muscle samples revealed decreased 2,4-dienoyl-CoA reductase activity when compared to normal controls. A second case with failure to thrive, developmental delay, lactic acidosis and severe encephalopathy was reported in 2014.

2,4-Dienoyl-CoA reductase deficiency was included as a secondary condition in the American College of Medical Genetics Recommended Uniform Panel for newborn screening. Its status as a secondary condition means there was not enough evidence of benefit to include it as a primary target, but it may be detected during the screening process or as part of a differential diagnosis when detecting conditions included as primary target. Despite its inclusion in newborn screening programs in several states for a number of years, no cases have been identified via neonatal screening.

Succinyl-CoA:3-oxoacid CoA transferase deficiency (SCOT deficiency) is an inborn error of ketone body utilization. Succinyl-CoA:3-oxoacid CoA transferase catalyzes the transfer of coenzyme A from succinyl-coenzyme A to acetoacetate. It can be caused by mutation in the "OXCT1" gene.

First described in 1972, more than 30 people have been reported in the medical literature with this inborn error of metabolism. They experience attacks of ketoacidosis during illness, and even when unwell may have elevated levels of ketone bodies in blood and urine (ketonemia and ketonuria, respectively). Not all people with SCOT deficiency have persistent ketonemia and ketonuria, particularly those with milder defects of enzyme activity.

The symptoms of Sly syndrome are similar to those of Hurler syndrome (MPS I). The symptoms include:

- in the head, neck, and face: coarse (Hurler-like) facies and macrocephaly, frontal prominence, premature closure of sagittal lambdoid sutures, and J-shaped sella turcica

- in the eyes: corneal opacity and iris coloboma

- in the nose: anteverted nostrils and a depressed nostril bridge

- in the mouth and oral areas: prominent alveolar processes and cleft palate

- in the thorax: usually pectus carinatum or exacavatum and oar-shaped ribs; also a protruding abdomen and inguinal or umbilical hernia

- in the extremities: talipes, an underdeveloped ilium, aseptic necrosis of femoral head, and shortness of tubular bones occurs

- in the spine: kyphosis or scoliosis and hook-like deformities in thoracic and lumbar vertebrate

- in the bones: dysostosis multiplex

In addition recurrent pulmonary infections occur. Hepatomegaly occurs in the gastrointestinal system. Splenomegaly occurs in the hematopoietic system. Inborn mucopolysaccharide metabolic disorders due to β-glucuronidase deficiency with granular inclusions in granulocytes occurs in the biochemical and metabolic systems. Growth and motor skills are affected, and mental retardation also occurs.

Urocanic aciduria, also called urocanate hydratase deficiency or urocanase deficiency, is an autosomal recessive metabolic disorder caused by a deficiency of the enzyme urocanase. It is a secondary disorder of histidine metabolism.

Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an under-recognized inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who first described the condition in 1951.

Direct sequence analysis of genomic DNA from blood can be used to perform a mutation analysis for the TALDO1 gene responsible for the Transaldolase enzyme.

Methylmalonyl-CoA mutase is a mitochondrial homodimer apoenzyme (EC. 5. 4.99.2) that focuses on the catalysis of methylmalonyl CoA to succinyl CoA. The enzyme is bound to adenosylcobalamin, a hormonal derivative of vitamin B12 in order to function. Methylmalonyl-CoA mutase deficiency is caused by genetic defect in the MUT gene responsible for encoding the enzyme. Deficiency in this enzyme accounts for 60% of the cases of methylmalonic acidemia.