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

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.

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.

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.

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.

Argininosuccinic aciduria, also called argininosuccinic acidemia, is an inherited disorder that causes the accumulation of argininosuccinic acid (also known as "ASA") in the blood and urine. Some patients may also have an elevation of ammonia, a toxic chemical, which can affect the nervous system. Argininosuccinic aciduria may become evident in the first few days of life because of high blood ammonia, or later in life presenting with "sparse" or "brittle" hair, developmental delay, and tremors.

An infant with argininosuccinic aciduria may seem lethargic or be unwilling to eat, have poorly controlled breathing rate or body temperature, experience seizures or unusual body movements, or go into a coma. Complications from argininosuccinic aciduria may include developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen. Immediate treatment and lifelong management (following a strict diet and using appropriate supplements) may prevent many of these complications.

Occasionally, an individual may inherit a mild form of the disorder in which ammonia accumulates in the bloodstream only during periods of illness or other stress.

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.

Organic acidemias are usually diagnosed in infancy, characterized by urinary excretion of abnormal amounts or types of organic acids. The diagnosis is usually made by detecting an abnormal pattern of organic acids in a urine sample by gas chromatography-mass spectrometry. In some conditions, the urine is always abnormal, in others the characteristic substances are only present intermittently. Many of the organic acidemias are detectable by newborn screening with tandem mass spectrometry.

These disorders vary in their prognosis, from manageable to fatal, and usually affect more than one organ system, especially the central nervous system.

Neurological damage and developmental delay are common factors in diagnosis, with associated symptoms ranging from poor feeding to slow growth, lethargy, vomiting,

dehydration, malnutrition, hypoglycemia, hypotonia, metabolic acidosis, ketoacidosis, hyperammonemia, and if left untreated, death.

Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity or decreased muscle tone and muscle weakness (which may be the result of secondary carnitine deficiency). Glutaric aciduria type 1, in many cases, can be defined as a cerebral palsy of genetic origins.

Babies with glutaric acidemia type 1 often are born with unusually large heads (macrocephaly). Macrocephaly is amongst the earliest signs of GA1. It is thus important to investigate all cases of macrocephaly of unknown origins for GCDH deficiency, given the importance of the early diagnosis of GA1.

Macrocephaly is a "pivotal clinical sign" of many neurological diseases. Physicians and parents should be aware of the benefits of investigating for an underlying neurological disorder, particularly a neurometabolic one, in children with head circumferences in the highest percentiles.

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.

Its hereditary form, an autosomal recessive disorder, can be caused by a deficiency in the enzyme UMPS, a bifunctional protein that includes the enzyme activities of orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase.

It can also arise secondary to blockage of the urea cycle, particularly in ornithine transcarbamylase deficiency (or OTC deficiency). This can be distinguished from hereditary orotic aciduria (seen above) by assessing blood ammonia levels and blood urea nitrogen (BUN). In OTC deficiency, hyperammonemia and decreased BUN are seen because the urea cycle is not functioning properly.

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.

3-Hydroxy-3-methylglutaryl-CoA lyase deficiency also referred to as HMG-CoA lyase deficiency or Hydroxymethylglutaric aciduria, is an uncommon inherited disorder in which the body cannot properly process the amino acid leucine. Additionally, the disorder prevents the body from making ketones, which are used for energy during fasting.

Propionic acidemia, also known as propionic aciduria, propionyl-CoA carboxylase deficiency and ketotic glycinemia, is an autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia.

The disorder presents in the early neonatal period with progressive encephalopathy. Death can occur quickly, due to secondary hyperammonemia, infection, cardiomyopathy, or basal ganglial stroke.

Propionic acidemia is a rare disorder that is inherited from both parents. Being autosomal recessive, neither parent shows symptoms, but both carry a defective gene responsible for this disease. It takes two faulty genes to cause PA, so there is a 1 in 4 chance for these parents to have a child with PA.

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.

1) Detection of orotic acid in urine

2) Deficiency of Enzymes orotate phosphoribosyl transferase and OMP decarboxylase

The signs/symptoms of this condition are consistent with the following:

- Intellectual disability,

- Muscular hypotonia

- Encephalitis

- Seizures

- Aphasia

2-hydroxyglutaric aciduria is an organic aciduria, and because of the stereoisomeric property of 2-hydroxyglutarate different variants of this disorder are distinguished:

Organic acidemia, also called organic aciduria, is a term used to classify a group of metabolic disorders which disrupt normal amino acid metabolism, particularly branched-chain amino acids, causing a buildup of acids which are usually not present.

The branched-chain amino acids include isoleucine, leucine and valine. Organic acids refer to the amino acids and certain odd-chained fatty acids which are affected by these disorders.

The four main types of organic acidemia are: methylmalonic acidemia, propionic acidemia, isovaleric acidemia, and maple syrup urine disease.

Hawkinsinuria, also called 4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency, is an autosomal dominant metabolic disorder affecting the metabolism of tyrosine. Normally, the breakdown of the amino acid tyrosine involves the conversion of 4-hydroxyphenylpyruvate to homogentisate by 4-Hydroxyphenylpyruvate dioxygenase. Complete deficiency of this enzyme would lead to tyrosinemia III. In rare cases, however, the enzyme is still able to produce the reactive intermediate 1,2-epoxyphenyl acetic acid, but is unable to convert this intermediate to homogentisate. The intermediate then spontaneously reacts with glutathione to form 2-L-cystein-S-yl-1,4-dihydroxy-cyclohex-5-en-1-yl acetic acid (hawkinsin).

Patients present with metabolic acidosis during the first year of life, which should be treated by a phenylalanine- and tyrosine-restricted diet. The tolerance toward these amino acids normalizes as the patients get older. Then only a chlorine-like smell of the urine indicates the presence of the condition, patients have a normal life and do not require treatment or a special diet.

The production of hawkinsin is the result of a gain-of-function mutation, inheritance of hawkinsinuria is therefore autosomal dominant (presence of a single mutated copy of the gene causes the condition). Most other inborn errors of metabolism are caused by loss-of-function mutations, and hence have recessive inheritance (condition occurs only if both copies are mutated).

D-Glyceric Acidemia should not be confused with L-Glyceric Acidemia (a.k.a. L-glyceric aciduria, a.k.a. primary hyperoxaluria type II ), which is associated with mutations in the "GRHPR" (encoding for the enzyme 'glyoxylate reductase/hydroxypyruvate reductase').

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.

Medium-chain acyl-CoA dehydrogenase deficiency, often known as MCAD deficiency or MCADD, is a disorder of fatty acid oxidation that impairs the body's ability to break down medium-chain fatty acids into acetyl-CoA. The disorder is characterized by hypoglycemia and sudden death without timely intervention, most often brought on by periods of fasting or vomiting.

Prior to expanded newborn screening, MCADD was an underdiagnosed cause of sudden death in infants. Individuals who have been identified prior to the onset of symptoms have an excellent prognosis.

MCADD is most prevalent in individuals of Northern European Caucasian descent, with an incidence of 1:4000 to 1:17,000 depending on the population. Treatment of MCADD is mainly preventative, by avoiding fasting and other situations where the body relies on fatty acid oxidation to supply energy.

Diagnostic methods

Diagnosis is based mainly on clinical findings and laboratory test results. Plasma concentrations of ammonia (>150 µmol/L) and citrulline (200-300 µmol/L) are elevated. Elevated levels of argininosuccinic acid (5-110 µmol/L) in the plasma or urine are diagnostic. Molecular genetic testing confirms diagnosis. Newborn screening for ASA is available in the U.S. and parts of Australia, and is considered in several European countries<