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.

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.

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.

Glycogen storage disease type III presents during infancy with hypoglycemia and failure to thrive. Clinical examination usually reveals hepatomegaly. Muscular disease, including hypotonia and cardiomyopathy, usually occurs later. The liver pathology typically regresses as the individual enter adolescence, as does splenomegaly, should the individual so develop it.

The clinical picture is heterogeneous and includes motor delay, seizures, moderate to severe mental retardation, absent speech, growth delay, muscular hypotonia and autistic features.

Glycogen storage disease type III is an autosomal recessive metabolic disorder and inborn error of metabolism (specifically of carbohydrates) characterized by a deficiency in glycogen debranching enzymes. It is also known as Cori's disease in honor of the 1947 Nobel laureates Carl Cori and Gerty Cori. Other names include Forbes disease in honor of clinician Gilbert Burnett Forbes (1915–2003), an American Physician who further described the features of the disorder, or limit dextrinosis, due to the limit dextrin-like structures in cytosol. Limit dextrin is the remaining polymer produced after hydrolysis of glycogen. Without glycogen debranching enzymes to further convert these branched glycogen polymers to glucose, limit dextrinosis abnormally accumulates in the cytoplasm.

Glycogen is a molecule the body uses to store carbohydrate energy. Symptoms of GSD-III are caused by a deficiency of the enzyme amylo-1,6 glucosidase, or debrancher enzyme. This causes excess amounts of an abnormal glycogen to be deposited in the liver, muscles and, in some cases, the heart.

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.

Quite often, the presenting symptom of ornithine aminotransferase (OAT) deficiency is myopia which progresses to night blindness. The onset of myopia is often in early childhood. Ophthalmological findings in affected individuals include constricted visual fields, posterior subcapsular cataracts (can begin in late teens), elevated dark adaptation thresholds and decreased or absent electroretinographic responses. Symptoms of OAT deficiency are progressive, and between the ages of 45 and 65, most affected individuals are almost completely blind.

In some cases, affected individuals will present in the neonatal period with disease that closely mimics a classic urea cycle defect, such as ornithine transcarbamylase deficiency, as the block in ornithine metabolism leads to secondary dysfunction of the urea cycle. These individuals present with hyperammonemia, poor feeding, failure to thrive and increased excretion of orotic acid.

Tyrosinemia or tyrosinaemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms include liver and kidney disturbances and intellectual disability. Untreated, tyrosinemia can be fatal.Most inborn forms of tyrosinemia produce hypertyrosinemia (high levels of tyrosine).

Aminoacylase 1 deficiency is a rare inborn error of metabolism. To date only 21 cases have been described.

Mutations in the FAH, TAT, or HPD gene cause a decrease in the activity of one of the enzymes in the breakdown of tyrosine.

As a result, tyrosine and its byproducts accumulate to toxic levels, which can cause damage and death to cells in the liver, kidneys, nervous system, and other organs.

Numerous genetic disorders are caused by errors in fatty acid metabolism. These disorders may be described as fatty oxidation disorders or as a "lipid storage disorders", and are any one of several inborn errors of metabolism that result from enzyme defects affecting the ability of the body to oxidize fatty acids in order to produce energy within muscles, liver, and other cell types.

Some of the more common fatty acid metabolism disorders are:

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.

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.

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.

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.

SLOS can present itself differently in different cases, depending on the severity of the mutation and other factors. Originally, SLOS patients were classified into two categories (classic and severe) based on external behaviours, physical characteristics, and other clinical features. Since the discovery of the specific biochemical defect responsible for SLOS, patients are given a severity score based on their levels of cerebral, ocular, oral, and genital defects. It is then used to classify patients as having mild, classical, or severe SLOS.

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

The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features ("e.g.," inverted nipples and subcutaneous fat pads; and strabismus. If an MRI is obtained, cerebellar atrophy and hypoplasia is a common finding.

Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic disc pallor, and reduced rod function on electroretinography.

Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.

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.

Sitosterolemia may share several clinical characteristics with the well-characterized familial hypercholesterolemia (FH), such as the development of tendon xanthomas in the first 10 years of life and the development of premature atherosclerosis . However, in contrast to FH patients, sitosterolemia patients usually have normal to moderately elevated total sterol levels and very high levels of plant sterols (sitosterol, campesterol, stigmasterol, avenosterol) and 5α-saturated stanols in their plasma. Plasma sitosterol levels in sitosterolemia patients are 10–25 times higher than in normal individuals (8–60 mg/dl). Not all patients with sitosterolemia have tendon xanthomas, thus absence of this should not be used to exclude this diagnosis.

Xanthomas may appear at any age, even in childhood. These may be present as subcutaneous xanthomas on the buttocks in children or in usual locations (e.g., Achilles tendon, extensor tendons of the hand) in children and adults. Xanthelasma and corneal arcus are less common. Decreased range of motion with possible redness, swelling, and warmth of joints due to arthritis may be present.In addition, sitosterolemia patients may develop hemolytic episodes and splenomegaly.

Untreated, the condition causes a significant increase in morbidity and mortality. Coronary heart disease and its inherent health consequences are the primary causes of illness and premature death in untreated patients.

This condition is suspected to result in liver dysfunction and cirrhosis, in the context of sitosterolemia, is reported

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

An example is lactose intolerance.

Carbohydrates account for a major portion of the human diet. These carbohydrates are composed of three principal monosaccharides: glucose, fructose and galactose; in addition glycogen is the storage form of carbohydrates in humans. The failure to effectively use these molecules accounts for the majority of the inborn errors of human carbohydrates metabolism.

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.

Neurologic signs and symptoms include progressively delayed development, weak muscle tone (hypotonia), seizures, and abnormal movements. The body's network of blood vessels is also affected. Children with this disorder may experience rashes of tiny red spots (petechiae) caused by bleeding under the skin and blue discoloration in the hands and feet due to reduced oxygen in the blood (acrocyanosis). Chronic diarrhea is another common feature of ethylmalonic encephalopathy. EE is often identified by urine organic acid analysis, the excretion of ethylmalonic acid, methylsuccinic acid, isobutyrylglycine and isovalerylglucine. Patients will also often have elevated thiosulphate concentration in their urine.

The signs and symptoms of ethylmalonic encephalopathy are apparent at birth or begin in the first few months of life. Problems with the nervous system typically worsen over time, and most affected individuals survive only into early childhood. A few children with a milder, chronic form of this disorder have been reported, and there can be considerable phenotypic variation, even within families. The life expectancy of individuals with EE is less than ten years.

Glycogen storage disease type IV, also known as Anderson’s Disease, is a form of glycogen storage disease, which is caused by an inborn error of metabolism. It is the result of a mutation in the GBE1 gene, which causes a defect in the glycogen branching enzyme. Therefore, glycogen is not made properly and abnormal glycogen molecules accumulate in cells; most severely in cardiac and muscle cells. The severity of this disease varies on the amount of enzyme produced. Glycogen Storage Disease Type IV is autosomal recessive, which means each parent has a mutant copy of the gene but show no symptoms of the disease. It affects 1 in 800,000 individuals worldwide, with 3% of all Glycogen Storage Diseases being type IV.