Pentosuria is a condition where the sugar xylitol, a pentose, presents in the urine in unusually high concentrations. It was characterized as an inborn error of carbohydrate metabolism in 1908. It is associated with a deficiency of L-xylulose reductase, necessary for xylitol metabolism. L-Xylulose is a reducing sugar, so it may give false diagnosis of diabetes, as it is found in high concentrations in urine. However glucose metabolism is normal in people with pentosuria, and they are not diabetic. Patients of pentosuria have a low concentration of the sugar d-xyloketose. Using, Phenyl pentosazone crystals, phloroglucin reaction, and absorption spectrum, pentose can be traced back as the reducing substance in urine, with those that have pentosuria.

Research has shown that pentosuria appears in 3 forms. The most widely studied is essential pentosuria, where a couple of grams of L-xylusol are released into a person’s system daily. L-xylulose reductase, contained in red blood cells, is composed of both a major and minor isozyme. For those diagnosed with essential pentosuria, the major isozyme appears to be the same as the minor one. Alimentary pentosuria can be acquired through fruits high in pentose. Finally, drug-induced pentosuria can be developed by those exposed to morphine, fevers, allergies, and some hormones.

Those diagnosed with Pentosuria are predominantly of Jewish root. However, it is a harmless defect, and no cure is needed.

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.

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.

Glutathionuria is the presence of glutathione in the urine, and is a rare inborn error of metabolism.

The condition has been identified in five patients.

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).

Clinical signs of PEM are variable depending on the area of the cerebral cortex affected and may include head pressing, dullness, opisthotonos, central blindness, anorexia, muscle tremors, teeth grinding, trismus, salivation, drooling, convulsions, nystagmus, clonic convulsions, and recumbency. Early administration of thiamine may be curative, but if the lesion is more advanced, then surviving animals may remain partially blind and mentally dull.

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.

Aldolase A deficiency, also called ALDOA deficiency, red cell aldolase deficiency or glycogen storage disease type 12 (GSD XII) is an autosomal recessive metabolic disorder resulting in a deficiency of the enzyme aldolase A; the enzyme is found predominantly in red blood cells and muscle tissue. The deficiency may lead to hemolytic anaemia as well as myopathy associated with exercise intolerance and rhabdomyolysis in some cases.

In undiagnosed and untreated children, the accumulation of precursor metabolites due to the deficient activity of galactose 1-phosphate uridylyltransferase (GALT) can lead to feeding problems, failure to thrive, liver damage, bleeding, and infections. The first presenting symptom in an infant is often prolonged jaundice. Without intervention in the form of galactose restriction, infants can develop hyperammonemia and sepsis, possibly leading to shock. The accumulation of galactitol and subsequent osmotic swelling can lead to cataracts which are similar to those seen in galactokinase deficiency. Long-term consequences of continued galactose intake can include developmental delay, developmental verbal dyspraxia, and motor abnormalities. Galactosemic females frequently suffer from ovarian failure, regardless of treatment in the form of galactose restriction.

Symptoms may include:

- Abnormal softening of the skull bone (craniotabes—infants and children)

- Blurred vision

- Bone pain or swelling

- Bulging fontanelle (infants)

- Changes in consciousness

- Decreased appetite

- Dizziness

- Double vision (young children)

- Drowsiness

- Headache

- Gastric mucosal calcinosis

- Heart valve calcification

- Hypercalcemia

- Increased intracranial pressure manifesting as cerebral edema, papilledema, and headache (may be referred to as Idiopathic intracranial hypertension)

- Irritability

- Liver damage

- Nausea

- Poor weight gain (infants and children)

- Skin and hair changes

- Cracking at corners of the mouth

- Hair loss

- Higher sensitivity to sunlight

- Oily skin and hair (seborrhea)

- Premature epiphyseal closure

- Skin peeling, itching

- Spontaneous fracture

- Yellow discoloration of the skin (aurantiasis cutis)

- Uremic pruritus

- Vision changes

- Vomiting

Inborn errors of metal metabolism refers to metabolic disturbances in the processing or distribution of dietary minerals.

An example is hemochromatosis.

No treatment is indicated for essential fructosuria, while the degree of fructosuria depends on the dietary fructose intake, it does not have any clinical manifestations. The amount of fructose routinely lost in urine is quite small. Other errors in fructose metabolism have greater clinical significance. Hereditary fructose intolerance, or the presence of fructose in the blood (fructosemia), is caused by a deficiency of aldolase B, the second enzyme involved in the metabolism of fructose. This enzyme deficiency results in an accumulation of fructose-1-phosphate, which inhibits the production of glucose and results in diminished regeneration of adenosine triphosphate. Clinically, patients with hereditary fructose intolerance are much more severely affected than those with essential fructosuria, with elevated uric acid, growth abnormalities and can result in coma if untreated.

Signs of vitamin E deficiency include the following:

- Neuromuscular problems-such as spinocerebellar ataxia and myopathies.

- Neurological problems-may include dysarthria, absence of deep tendon reflexes, loss of the ability to sense vibration and detect where body parts are in three dimensional space, and positive Babinski sign.

- Hemolytic anemia-due to oxidative damage to red blood cells

- Retinopathy

- Impairment of the immune response

There is also some laboratory evidence that vitamin E deficiency can cause male infertility.

A diagnosis of essential fructosuria is typically made after a positive test for reducing substances in the urine. The excretion of fructose in the urine is not constant, it depends largely on dietary intake.

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.

Polioencephalomalacia (PEM), also referred to as cerebrocortical necrosis (CCN), is a neurological disease seen in ruminants that is caused by disrupted thiamine production in the body. Thiamine is a key chemical in glucose metabolism that, when definicient, is most threatening to neurological activity. Cattles, sheep, goat, and other ruminants that are diagnosed with PEM or pre-PEM suffer opishotonus, cortical blindness, disoriented movement, and eventually fatality, if left untreated. Current data shows that the onset of PEM can range from birth to late adulthood.

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.

Vitamin E deficiency or hypovitaminosis E is a deficiency of vitamin E. It causes nerve problems due to poor conduction of electrical impulses along nerves due to changes in nerve membrane structure and function.

Galactose-1-phosphate uridylyltransferase deficiency, also called galactosemia type 1, classic galactosemia or GALT deficiency, is the most common type of galactosemia, an inborn error of galactose metabolism, caused by a deficiency of the enzyme galactose-1-phosphate uridylyltransferase. It is an autosomal recessive metabolic disorder that can cause liver disease and death if untreated. Treatment of galactosemia is most successful if initiated early and includes dietary restriction of lactose intake. Because early intervention is key, galactosemia is included in newborn screening programs in many areas. On initial screening, which often involves measuring the concentration of galactose in blood, classic galactosemia may be indistinguishable from other inborn errors of galactose metabolism, including galactokinase deficiency and galactose epimerase deficiency. Further analysis of metabolites and enzyme activities are needed to identify the specific metabolic error.

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

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.

Inborn errors of purine–pyrimidine metabolism are a class of inborn error of metabolism disorders specifically affecting purine metabolism and pyrimidine metabolism. An example is Lesch–Nyhan syndrome.

Urine tests may be of use in identifying some of these disorders.

Mauriac syndrome is a rare complication of diabetes mellitus type 1 characterized by extreme hepatomegaly due to glycogen deposition, along with growth failure and delayed puberty. It occurs in children and adolescents with type 1 diabetes as a result of abnormally high blood sugar levels and the symptoms tend to rectify with attainment of normal blood sugar levels. Abnormally high blood sugar levels are relatively common among patients with type I diabetes, but Mauriac syndrome is rare suggesting that a factor affecting glycogen metabolism in addition to the high level of blood sugar is necessary to cause the syndrome. A study of an adolescent boy with severe Mauriac syndrome found a mutation in PHKG2 which is the catalytic subunit of glycogen phosphorylase kinase (PhK). PhK is a large enzyme complex responsible for the activation of glycogen phosphorylase, the first enzyme in the pathway of glycogen metabolism. Expression of the mutant PHKG2 in a human liver cell line inhibited the enzyme activity of the PhK complex and increased glycogen levels. The mother of the boy with Mauriac syndrome possessed the mutant PHKG2, but did not have diabetes or a clinically detectable enlarged liver. The father of the boy had type 1 diabetes with abnormally high blood sugar levels and the size of his liver and his growth were normal. The study suggests that a mutant enzyme of glycogen metabolism in addition to an abnormally high blood glucose level is necessary to cause Mauriac syndrome.

Inborn errors of amino acid metabolism are metabolic disorders which impair the synthesis and degradation of amino acids.

Remarks:

- Some GSDs have different forms, e.g. infantile, juvenile, adult (late-onset).

- Some GSDs have different subtypes, e.g. GSD1a / GSD1b, GSD9A1 / GSD9A2 / GSD9B / GSD9C / GSD9D.

- GSD type 0: Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified with the GSDs as type 0 because it is another defect of glycogen storage and can cause similar problems.

- GSD type VIII (GSD 8): In the past it was considered a distinct condition, however it is now classified with GSD type VI or GSD IXa1; it has been described as X-linked recessive inherited.

- GSD type XI (GSD 11): Fanconi-Bickel syndrome, hepatorenal glycogenosis with renal Fanconi syndrome, no longer considered a glycogen storage disease.

- GSD type XIV (GSD 14): Now classed as Congenital disorder of glycosylation type 1 (CDG1T), affects the phosphoglucomutase enzyme (gene PGM1).

- Lafora disease is considered a complex neurodegenerative disease and also a glycogen metabolism disorder.