Diagnosis typically occurs during the first 6 months of life due to characteristic neurological symptoms. These symptoms include muscle spasms, tetany, and seizures. Laboratory testing indicates hypomagnesemia (decreased serum magnesium levels), hypocalcemia (decreased serum calcium levels), and little to no measurable parathyroid hormone levels. Diagnosis is confirmed with these symptoms and can be further solidified with genetic sequencing of the TRPM6 gene.

Hypomagnesemia with secondary hypocalcemia (HSH) is an autosomal recessive genetic disorder affecting intestinal magnesium absorption. Decreased intestinal magnesium reabsorption and the resulting decrease in serum magnesium levels is believed to cause lowered parathyroid hormone (PTH) output by the parathyroid gland. This results in decreased PTH and decreased serum calcium levels (hypocalcemia). This manifests in convulsions and spasms in early infancy which, if left untreated, can lead to mental retardation or death. HSH is caused by mutations in the TRPM6 gene.

Some of the possible symptoms that can occur with metabolic disorders are: lethargy, weight loss, jaundice, seizures, to name a few. The symptoms expressed would vary with the type of metabolic disorder. There are four categories of symptoms: acute symptoms, late-onset acute symptoms, progressive general symptoms and permanent symptoms.

Hypertryptophanemia, also called familial hypertryptophanemia, is a rare autosomal recessive metabolic disorder that results in a massive buildup of the amino acid tryptophan in the blood, with associated symptoms and tryptophanuria ("-uria" denotes "in the urine").

Elevated levels of tryptophan are also seen in Hartnup disease, a disorder of amino acid transport. However, the increase of tryptophan in that disorder is negligible when compared to that of hypertryptophanemia.

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.

Affected individuals may not have symptoms in some cases. Symptomatic individuals present with symptoms identical to those of patients who are on thiazide diuretics, given that the affected transporter is the exact target of thiazides.

Clinical signs of Gitelman syndrome include a high blood pH in combination with low levels of chloride, potassium, and magnesium in the blood and decreased calcium excretion in the urine. In contrast to people with Gordon's syndrome, those affected by Gitelman's syndrome generally have low or normal blood pressure. Individuals affected by Gitelman's syndrome often complain of severe muscle cramps or weakness, numbness, thirst, waking up at night to urinate, salt cravings, abnormal sensations, chondrocalcinosis, or weakness expressed as extreme fatigue or irritability. More severe symptoms such as seizures, tetany, and paralysis have been reported. Abnormal heart rhythms and a prolonged QT interval can be detected on electrocardiogram and cases of sudden cardiac death have been reported due to low potassium levels. Phenotypic variations observed among patients probably result from differences in their genetic background and may depend on which particular amino acid in the NCCT protein has been mutated.

Histidinemia is considered benign as most patients remain asymptomatic, early correlational evidence from the first decade of histidinemia research lead to the theory that histidinemia was associated with multiple developmental symptoms including hyperactivity, speech impediment, developmental delay, learning difficulties, and sometimes mental retardation. However, these claims were later deemed coincidental as a large subpopulation of infants that tested positive for histidinemia were found to have normal IQ and speech characteristics; as such histidinemia has since been reclassified as a benign inborn error of metabolism.

A number of abnormalities and symptoms have been observed with hypertryptophanemia.

Musculoskeletal effects include: joint contractures of the elbows and interphalangeal joints of the fingers and thumbs (specifically the distal phalanges), pes planus (fallen arches), an ulnar drift affecting the fingers of both hands (an unusual, yet correctible feature where the fingers slant toward the ulnar side of the forearm), joint pain and laxity, and adduction of the thumbs (where the thumb appears drawn into the palm, related to contracture of the adductor pollicis).

Behavioral, developmental and other anomalies often include: hypersexuality, perceptual hypersensitivity, emotional lability (mood swings), hyperaggressive behavior; hypertelorism (widely-set eyes),

optical strabismus (misalignment) and myopia.

Metabolically, hypertryptophanemia results in tryptophanuria and exhibits significantly elevated serum levels of tryptophan, exceeding 650% of maximum (normal range: 25-73 micromole/l) in some instances.

A product of the bacterial biosynthesis of tryptophan is indole. The excess of tryptophan in hypertryptophanemia also results in substantial excretion of indoleic acids. These findings suggest a possible congenital defect in the metabolic pathway where tryptophan is converted to kynurenine.

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.

Although many people with a defective AMPD gene are asymptomatic, others may have symptoms such as exercise intolerance, muscle pain, and muscle cramping.

- Fatigue

- MADD lowers aerobic power output, so increased anaerobic power is needed to perform the same amount of work.

- Without myoadenlyate deaminase, heavy activity causes adenosine to be released into the cell or perfused into the surrounding tissues. Fatigue and sedation after heavy exertion can be caused by excess adenosine in the cells which signals muscle fiber to feel fatigued. In the brain, excess adenosine decreases alertness and causes sleepiness. In this way, adenosine may play a role in fatigue from MADD.

- Recovery from over-exertion can be hours, days or even months. In cases of rhabdomyolysis, which is the rapid breakdown of muscle fibers, time to recovery is dependent on duration and intensity of original activity plus any excess activity during the recovery period.

- Muscle pain

- Muscle pain from MADD is not well understood, but is partially due to high levels of lactate. Increased levels of free adenosine temporarily decrease pain, allowing over-exertion without awareness. The over exertion can cause mild to severe cases of rhabdomyolysis, which is painful.

- Adenosine mediates pain through adenosine receptors. MADD causes an increase of free adenosine during heavy activity which may cause exercise-induced muscle pain. Over time, excess free adenosine down-regulates primary A1 adenosine receptors, leading to increased muscle pain. Secondary receptors (A3) increase peripheral inflammation, which also increases pain.

- Muscle cramping

- The cause of cramping is unknown, but may be related to elevated lactate, increased calcium signaling across the sarcoplasmic reticulum caused by membrane instability from reduced levels of ATP, or increased levels of free adenosine.

- Muscle weakness

- Muscle weakness is not a major symptom, though the progressive effects of chronic muscle damage from rhabdomyolysis will eventually cause significant weakness. Similarly, the long-term metabolic effects may result in nerve damage.

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

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.

Histidinemia, also referred to as histidinuria, is a rare autosomal recessive metabolic disorder caused by a deficiency of the enzyme histidase. Histidase is needed for the metabolism of the amino acid histidine. Although originally thought to be linked to multiple developmental disorders histidinemia is now accepted as a relatively benign disorder, leading to a reduction in the prevalence of neonatal screening procedures.

Gitelman syndrome is an autosomal recessive kidney disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. The disorder is caused by genetic mutations resulting in improper function of the thiazide-sensitive sodium-chloride symporter (also known as NCC, NCCT, or TSC) located in the distal convoluted tubule of the kidney. This symporter is a channel responsible for the transport of multiple electrolytes such as sodium, chloride, calcium, magnesium, and potassium.

Gitelman syndrome was formerly considered a subset of Bartter syndrome until the distinct genetic and molecular bases of these disorders were identified. Bartter syndrome is also an autosomal recessive hypokalemic metabolic alkalosis, but it derives from a mutation to the NKCC2 found in the thick ascending limb of the loop of Henle.

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).

Lactic acidosis is a medical condition characterized by the buildup of lactate (especially L-lactate) in the body, which results in an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body's metabolism of lactic acid.

Lactic acidosis is typically the result of an underlying acute or chronic medical condition, medication, or poisoning. The symptoms are generally attributable to these underlying causes, but may include nausea, vomiting, rapid deep breathing, and generalised weakness.

The diagnosis is made on biochemical analysis of blood (often initially on arterial blood gas samples), and once confirmed, generally prompts an investigation to establish the underlying cause to treat the acidosis. In some situations, hemofiltration (purification of the blood) is temporarily required. In rare chronic forms of lactic acidosis caused by mitochondrial disease, a specific diet or dichloroacetate may be used. The prognosis of lactic acidosis depends largely on the underlying cause; in some situations (such as severe infections), it indicates an increased risk of death.

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.

A metabolic disorder can happen when abnormal chemical reactions in the body alter the normal metabolic process. It can also be defined as inherited single gene anomaly, most of which are autosomal recessive.

Lactic acidosis is commonly found in people who are unwell, such as those with severe heart and/or lung disease, a severe infection with sepsis, the systemic inflammatory response syndrome due to another cause, severe physical trauma, or severe depletion of body fluids. Symptoms in humans include all those of typical metabolic acidosis (nausea, vomiting, generalized muscle weakness, and rapid breathing).

The low incidence of this syndrome is often related to aldolase A's essential glycolytic role along with its exclusive expression in blood and skeletal muscle. Early developmental reliance and constitutive function prevents severe mutation in successful embryos. Infrequent documentation thus prevents clear generalisation of symptoms and causes. However five cases have been well described. ALDOA deficiency is diagnosed through reduced aldoA enzymatic activity, however, both physiological response and fundamental causes vary.

Magnesium deficiency is a nutritional deficiency which can affect both plants and animals

Magnesium deficiency may refer to:

- Magnesium deficiency (plants)

- Magnesium deficiency (medicine)

- For the specific condition of low blood magnesium levels, see Hypomagnesemia

Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrates) into others (products). In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or to the effects of reduced ability to synthesize essential compounds. Inborn errors of metabolism are now often referred to as congenital metabolic diseases or inherited metabolic diseases.

The term "inborn error of metabolism" was coined by a British physician, Archibald Garrod (1857–1936), in 1908. He is known for work that prefigured the "one gene-one enzyme" hypothesis, based on his studies on the nature and inheritance of alkaptonuria. His seminal text, "Inborn Errors of Metabolism" was published in 1923.

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.

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.

Symptoms of congenital Type III Galactosemia are apparent from birth, but vary in severity depending on whether the peripheral or generalized disease form is present. Symptoms may include:

- Infantile jaundice

- Infantile hypotonia

- Dysmorphic features

- Sensorineural hearing loss

- Impaired growth

- Cognitive deficiencies

- Depletion of cerebellar Purkinje cells

- Ovarian failure (POI) and hypertrophic hypergonadism

- Liver failure

- Renal failure

- Splenomegaly

- Cataracts

Studies of Type III galactosemia symptoms are mostly descriptive, and precise pathogenic mechanisms remain unknown. This is largely due to a lack of functional animal models of classic galactosemia. The recent development of a "Drosophila melanogaster" GALE mutant exhibiting galactosemic symptoms may yield a promising future animal model.