The disease is named for the presence of sweet-smelling urine, an odor similar to that of maple syrup, when the person goes into metabolic crisis. The smell is also present and sometimes stronger in the ear wax of an affected individual at these times. In populations to whom maple syrup is unfamiliar, the aroma can be likened to fenugreek, and fenugreek ingestion may impart the aroma to urine.

Infants with this disease seem healthy at birth but quickly deteriorate, often with severe brain damage, which may be permanent. Death often occurs within the first five months in severe cases of the disease, when left untreated.

Hartnup disease manifests during infancy with variable clinical presentation: failure to thrive, photosensitivity, intermittent ataxia, nystagmus, and tremor.

Nicotinamide is necessary for neutral amino acid transporter production in the proximal renal tubules found in the kidney, and intestinal mucosal cells found in the small intestine. Therefore, a symptom stemming from this disorder results in increased amounts of amino acids in the urine.

Pellagra, a similar condition, is also caused by low nicotinamide; this disorder results in dermatitis, diarrhea, and dementia.

Hartnup disease is a disorder of amino acid transport in the intestine and kidneys; otherwise, the intestine and kidneys function normally, and the effects of the disease occur mainly in the brain and skin. Symptoms may begin in infancy or early childhood, but sometimes they begin as late as early adulthood. Symptoms may be triggered by sunlight, fever, drugs, or emotional or physical stress. A period of poor nutrition nearly always precedes an attack. The attacks usually become progressively less frequent with age. Most symptoms occur sporadically and are caused by a deficiency of niacinamide. A rash develops on parts of the body exposed to the sun. Mental retardation, short stature, headaches, unsteady gait, and collapsing or fainting are common. Psychiatric problems (such as anxiety, rapid mood changes, delusions, and hallucinations) may also result.

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.

Because of the enormous number of these diseases and wide range of systems affected, nearly every "presenting complaint" to a doctor may have a congenital metabolic disease as a possible cause, especially in childhood. The following are examples of potential manifestations affecting each of the major organ systems.

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

This defect leads to a multi-systemic disorder of the connective tissue, muscles, central nervous system (CNS), and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague.

Signs and symptoms of homocystinuria that may be seen include the following:

The term fatty acid oxidation disorder (FAOD) is sometimes used, especially when there is an emphasis on the oxidation of the fatty acid.

In addition to the fetal complications, they can also cause complications for the mother during pregnancy.

Examples include:

- trifunctional protein deficiency

- MCADD, LCHADD, and VLCADD

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.

A broad classification for genetic disorders that result from an inability of the body to produce or utilize one enzyme that is required to oxidize fatty acids. The enzyme can be missing or improperly constructed, resulting in it not working. This leaves the body unable to produce energy within the liver and muscles from fatty acid sources.

The body's primary source of energy is glucose; however, when all the glucose in the body has been expended, a normal body digests fats. Individuals with a fatty-acid metabolism disorder are unable to metabolize this fat source for energy, halting bodily processes. Most individuals with a fatty-acid metabolism disorder are able to live a normal active life with simple adjustments to diet and medications.

If left undiagnosed many complications can arise. When in need of glucose the body of a person with a fatty-acid metabolism disorder will still send fats to the liver. The fats are broken down to fatty acids. The fatty acids are then transported to the target cells but are unable to be broken down, resulting in a build-up of fatty acids in the liver and other internal organs.

Fatty-acid metabolism disorders are sometimes classified with the lipid metabolism disorders, but in other contexts they are considered a distinct category.

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.

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 hypermethioninemia often do not show any symptoms. Some individuals with hypermethioninemia exhibit learning disabilities, mental retardation, and other neurological problems; delays in motor skills such as standing or walking; sluggishness; muscle weakness; liver problems; unusual facial features; and their breath, sweat, or urine may have a smell resembling boiled cabbage.

Hypermethioninemia can occur with other metabolic disorders, such as homocystinuria, tyrosinemia and galactosemia, which also involve the faulty breakdown of particular molecules. It can also result from liver disease or excessive dietary intake of methionine from consuming large amounts of protein or a methionine-enriched infant formula.

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.

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.

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.

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.

Traditionally the inherited metabolic diseases were classified as disorders of carbohydrate metabolism, amino acid metabolism, organic acid metabolism, or lysosomal storage diseases. In recent decades, hundreds of new inherited disorders of metabolism have been discovered and the categories have proliferated. Following are some of the major classes of congenital metabolic diseases, with prominent examples of each class. Many others do not fall into these categories.

The signs and symptoms of beta-ketothiolase deficiency include vomiting, dehydration, trouble breathing, extreme tiredness, and occasionally convulsions. These episodes are called ketoacidotic attacks and can sometimes lead to coma. Attacks occur when compounds called organic acids (which are formed as products of amino acid and fat breakdown) build up to toxic levels in the blood. These attacks are often triggered by an infection, fasting (not eating), or in some cases, other types of stress.

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.

Isovaleric acidemia is a rare autosomal recessive metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine. It is a classical type of organic acidemia.

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.

Beta-ketothiolase deficiency is a rare, autosomal recessive metabolic disorder in which the body cannot properly process the amino acid isoleucine or the products of lipid breakdown.

The typical age of onset for this disorder is between 6 months and 24 months.

Classical homocystinuria, also known as cystathionine beta synthase deficiency or CBS deficiency, is an inherited disorder of the metabolism of the amino acid methionine, often involving cystathionine beta synthase. It is an inherited autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from both parents to be affected.

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.