Type A, which has been identified mostly in people from North America, has moderately severe symptoms that begin in infancy. Characteristic features include developmental delay and a buildup of lactic acid in the blood (lactic acidosis). Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. In some cases, episodes of lactic acidosis are triggered by an illness or periods without food. Children with pyruvate carboxylase deficiency type A typically survive only into early childhood.

Pyruvate carboxylase deficiency type B has life-threatening signs and symptoms that become apparent shortly after birth. This form of the condition has been reported mostly in Europe, particularly France. Affected infants have severe lactic acidosis, a buildup of ammonia in the blood (hyperammonemia), and liver failure. They experience neurological problems including weak muscle tone (hypotonia), abnormal movements, seizures, and coma. Infants with this form of the condition usually survive for less than 3 months after birth.

Infants with this disorder appear normal at birth but usually develop signs and symptoms during the first year of life or in early childhood. The characteristic features of this condition, which can range from mild to life-threatening, include feeding difficulties, recurrent episodes of vomiting and diarrhea, excessive tiredness (lethargy), and weak muscle tone (hypotonia). If untreated, this disorder can lead to delayed development, seizures, and coma. Early detection and lifelong management (following a low-protein diet and using appropriate supplements) may prevent many of these complications. In some cases, people with gene mutations that cause 3-methylcrotonyl-CoA carboxylase deficiency never experience any signs or symptoms of the disorder.

The characteristic features of this condition are similar to those of Reye syndrome, a severe disorder that develops 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.

Signs and symptoms of a biotinidase deficiency can appear several days after birth. These include seizures, hypotonia and muscle/limb weakness, ataxia, paresis, hearing loss, optic atrophy, skin rashes (including seborrheic dermatitis and psoriasis), and alopecia. If left untreated, the disorder can rapidly lead to coma and death.

Biotinidase deficiency can also appear later in life. This is referred to as "late-onset" biotinidase deficiency. The symptoms are similar, but perhaps more mild, because if an individual survives the neonatal period they likely have some residual activity of biotin-related enzymes. Studies have noted individuals who were asymptomatic until adolescence or early adulthood. One study pointed out that untreated individuals may not show symptoms until age 21. Furthermore, in rare cases, even individuals with profound deficiencies of biotinidase can be asymptomatic.

Symptom severity is predictably correlated with the severity of the enzyme defect. Profound biotinidase deficiency refers to situations where enzyme activity is 10% or less. Individuals with partial biotinidase deficiency may have enzyme activity of 10-30%.

Functionally, there is no significant difference between dietary biotin deficiency and genetic loss of biotin-related enzyme activity. In both cases, supplementation with biotin can often restore normal metabolic function and proper catabolism of leucine and isoleucine.

The symptoms of biotinidase deficiency (and dietary deficiency of biotin) can be quite severe. A 2004 case study from Metametrix detailed the effects of biotin deficiency, including aggression, cognitive delay, and reduced immune function.

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.

Multiple carboxylase deficiency is a form of metabolic disorder involving failures of carboxylation enzymes.

The deficiency can be in biotinidase or holocarboxylase synthetase.

These conditions respond to biotin.

Forms include:

- Holocarboxylase synthetase deficiency - neonatal;

- Biotinidase deficiency - late onset;

If left untreated, the symptoms can include feeding problems, decreased body tone, generalized red rash with skin exfoliation and baldness, failure to thrive, seizure, coma, developmental delay, foul smelling urine, lactic acidosis, and high levels of ketones and ammonia in the blood.

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.

The signs and symptoms of this disorder typically appear in early childhood. Almost all affected children have delayed development. Additional signs and symptoms can include weak muscle tone (hypotonia), seizures, diarrhea, vomiting, and low blood sugar (hypoglycemia). A heart condition called cardiomyopathy, which weakens and enlarges the heart muscle, is another common feature of malonyl-CoA decarboxylase deficiency.

Some common symptoms in Malonyl-CoA decarboxylase deficiency, such as cardiomyopathy and metabolic acidosis, are triggered by the high concentrations of Malonyl-CoA in the cytoplasm. High level of Malonyl-CoA will inhibits β-oxidation of fatty acids through deactivating the carrier of fatty acyl group, CPT1, and thus, blocking fatty acids from going into the mitochondrial matrix for oxidation.

A research conducted in Netherlands has suggested that carnitine supplements and a low fat diet may help to reduce the level of malonic acid in our body.

A characteristic feature of isovaleric acidemia is a distinctive odor of sweaty feet. This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.

In about half of cases, the signs and symptoms of this disorder become apparent within a few days after birth and include poor feeding, vomiting, seizures, and lack of energy that can progress to coma. These medical problems are typically severe and can be life-threatening. In the other half of cases, the signs and symptoms of the disorder appear during childhood and may come and go over time. They are often triggered by an infection or by eating an increased amount of protein-rich foods.

SBCADD is included as a secondary target condition in most newborn screening programs, as the key analyte is the same as is used to identify isovaleric acidemia. Most cases have been Hmong individuals, who are asymptomatic. There are isolated case reports where individuals have been identified with SBCADD in addition to developmental delay and epilepsy. It is currently unclear what the complete clinical presentation of SBCADD looks like. There is some concern that these cases with additional symptoms may reflect an ascertainment bias rather than being a true representation of the clinical spectrum of the disease. Currently, there is no accepted treatment, as most affected individuals do not require any. Some recommend avoidance of valproic acid, as it can be a substrate for 2-methylbutyryl-CoA dehydrogenase.

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.

The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onset varies. Affected infants often have immunodeficiency diseases, difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). Immediate treatment and lifelong management (using biotin supplements) may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizures, and coma. These medical problems may be life-threatening in some cases.

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.

The presentation of patient with SPCD can be incredibly varied, from asymptomatic to lethal cardiac manifestations. Early cases were reported with liver dysfunction, muscular findings (weakness and underdevelopment), hypoketotic hypoglycemia, cardiomegaly, cardiomyopathy and marked carnitine deficiency in plasma and tissues, combined with increased excretion in urine. Patients who present clinically with SPCD fall into two categories, a metabolic presentation with hypoglycemia and a cardiac presentation characterized by cardiomyopathy. Muscle weakness can be found with either presentation.

In countries with expanded newborn screening, SPCD can be identified shortly after birth. Affected infants show low levels of free carnitine and all other acylcarnitine species by tandem mass spectrometry. Not all infants with low free carnitine are affected with SPCD. Some may have carnitine deficiency secondary to another metabolic condition or due to maternal carnitine deficiency. Proper follow-up of newborn screening results for low free carnitine includes studies of the mother to determine whether her carnitine deficiency is due to SPCD or secondary to a metabolic disease or diet. Maternal cases of SPCD have been identified at a higher than expected rate, often in women who are asymptomatic. Some mothers have also been identified through newborn screening with cardiomyopathy that had not been previously diagnosed. The identification and treatment of these asymptomatic individuals is still developing, as it is not clear whether they require the same levels of intervention as patients identified with SPCD early in life based on clinical presentation.

Biotinidase deficiency is an autosomal recessive metabolic disorder in which biotin is not released from proteins in the diet during digestion or from normal protein turnover in the cell. This situation results in biotin deficiency.

Biotin, also called vitamin B, is an important water-soluble nutrient that aids in the metabolism of fats, carbohydrates, and proteins. Biotin deficiency can result in behavioral disorders, lack of coordination, learning disabilities and seizures. Biotin supplementation can alleviate and sometimes totally stop such symptoms.

This exclusively myopathic form is the most prevalent and least severe phenotypic presentation of this disorder. Characteristic signs and symptoms include rhabdomyolysis (breakdown of muscle fibers and subsequent release of myoglobin), myoglobinuria, recurrent muscle pain, and weakness. It is important to note that muscle weakness and pain typically resolves within hours to days, and patients appear clinically normal in the intervening periods between attacks. Symptoms are most often exercise-induced, but fasting, a high-fat diet, exposure to cold temperature, or infection (especially febrile illness) can also provoke this metabolic myopathy. In a minority of cases, disease severity can be exacerbated by three life-threatening complications resulting from persistent rhabdomyolysis: acute kidney failure, respiratory insufficiency, and episodic abnormal heart rhythms. Severe forms may have continual pain from general life activity. The adult form has a variable age of onset. The first appearance of symptoms usually occurs between 6 and 20 years of age but has been documented in patients as young as 8 months as well as in adults over the age of 50. Roughly 80% cases reported to date have been male.

There are three main types of carnitine palmitoyltransferase II deficiency classified on the basis of tissue-specific symptomotology and age of onset:

- Mild to severe adult myopathic form

- Severe infantile multisystemic form

- Lethal neonatal form

It should be noted that among the few people diagnosed with CPT2, some have unknown and/or novel mutations that place them outside these three categories while remaining positive for CPT2.

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.

Holocarboxylase synthetase deficiency is an inherited metabolic disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, a group of disorders characterized by impaired activity of certain enzymes that depend on biotin. Symptoms are very similar to biotinidase deficiency and treatment – large doses of biotin – is also the same.

Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomiting, dehydration, acidosis, low muscle tone (hypotonia), seizures, and lethargy. The effects of propionic acidemia quickly become life-threatening.

3-Methylcrotonyl-CoA carboxylase deficiency (3MCC deficiency), also known as 3-Methylcrotonylglycinuria or BMCC deficiency is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have inadequate levels of an enzyme that helps break down proteins containing the amino acid leucine. This condition affects an estimated 1 in 50,000 individuals worldwide.

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

Systemic primary carnitine deficiency (SPCD), also known as carnitine uptake defect, carnitine transporter deficiency (CTD) or systemic carnitine deficiency is an inborn error of fatty acid transport caused by a defect in the transporter responsible for moving carnitine across the plasma membrane. Carnitine is an important amino acid for fatty acid metabolism. When carnitine cannot be transported into tissues, fatty acid oxidation is impaired, leading to a variety of symptoms such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. The specific transporter involved with SPCD is OCTN2, coded for by the "SLC22A5" gene located on chromosome 5. SPCD is inherited in an autosomal recessive manner, with mutated alleles coming from both parents.

Acute episodes due to SPCD are often preceded by metabolic stress such as extended fasting, infections or vomiting. Cardiomyopathy can develop in the absence of an acute episode, and can result in death. SPCD leads to increased carnitine excretion in the urine and low levels in plasma. In most locations with expanded newborn screening, SPCD can be identified and treated shortly after birth. Treatment with high doses of carnitine supplementation is effective, but needs to be rigorously maintained for life.

SPCD is more common in the Faroe Islands than in other countries, at least one out of every 1000 inhabitants of the Faroes has the illness, while the numbers for other countries are one in every 100,000. Around 100 persons in the islands have been diagnosed, around one third of the whole population of 48,000 people have been screened for SPCD. Several young Faroese people and children have died a sudden death with cardiac arrest because of SPCD. Scientists believe that around 10% of the Faroese population are carriers of the gene for SPCD. These people are not ill, but may have a lower amount of carnitine in their blood than non-carriers.

This disorder usually appears within the first year of life. The signs and symptoms of HMG-CoA lyase deficiency include vomiting, dehydration, lethargy, convulsions, and coma. When episodes occur in an infant or child, blood sugar becomes extremely low (hypoglycemia), and harmful compounds can build up and cause the blood to become too acidic (metabolic acidosis). These episodes are often triggered by an infection, fasting, strenuous exercise, or sometimes other types of stress.

Malonyl-CoA decarboxylase deficiency (MCD), or Malonic aciduria is an autosomal-recessive metabolic disorder caused by a genetic mutation that disrupts the activity of Malonyl-Coa decarboxylase. This enzyme breaks down Malonyl-CoA (a fatty acid precursor and a fatty acid oxidation blocker) into Acetyl-CoA and carbon dioxide.