Signs and symptoms of CTLN1 in infants are caused by increasing levels of ammonia in the blood and cerebrospinal fluid and include excessive vomiting, anorexia, refusal to eat, irritability, increased intracranial pressure, and worsening lethargy, seizures, hypotonia, respiratory distress, hepatomegaly, and cerebral edema. These symptoms appear within days of birth in the more severe forms of the disease with complete deficiency of the enzyme. As ammonia accumulates further, the affected infant may enter a hyperammonemic coma, which indicates neurological damage and can cause developmental delays, cognitive disabilities, cerebral palsy, hypertonia, spasticity, ankle clonus, seizures, and liver failure.

Milder forms of the disease are caused by partial arginosuccinate synthetase deficiency and may manifest in childhood or in adulthood. Symptoms of mild CTLN1 include failure to thrive, avoidance of high-protein foods, ataxia, worsening lethargy, and vomiting. Hyperammonemic coma can still develop in these people. CTLN1 can also develop in the perinatal period.

Citrullinemia type I (CTLN1), also known as arginosuccinate synthetase deficiency, is a rare disease caused by a deficiency in argininosuccinate synthetase, an enzyme involved in excreting excess nitrogen from the body. There are mild and severe forms of the disease, which is one of the urea cycle disorders.

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.

Type 1 usually begins somewhere in the first three to 18 months of age and in considered the most severe of the three types. Symptoms include:

- Coarse facial features

- Enlarged liver, spleen, and/or heart

- Intellectual disability

- Seizures

- Abnormal bone formation of many bones

- Progressive deterioration of brain and spinal cord

- Increased or decreased perspiration

Patients have no vascular lesions, but have rapid psychomotor regression, severe and rapidly progressing neurologic signs, elevated sodium and chloride excretion in the sweat, and fatal outcome before the sixth year.

Type I citrullinemia (, also known as classic citrullinemia) usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up in the body, they develop a lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. These medical problems can be life-threatening in many cases. A milder form of type I citrullinemia is less common in childhood or adulthood. Some people with gene mutations that cause type I citrullinemia never experience signs and symptoms of the disorder.

Type I citrullinemia is the most common form of the disorder, affecting about one in 57,000 births worldwide. Mutations in the "ASS" gene cause type I citrullinemia. The enzyme made by this gene, argininosuccinate synthetase (), is responsible for one step of the urea cycle. Mutations in the "ASS" gene reduce the activity of the enzyme, which disrupts the urea cycle and prevents the body from processing nitrogen effectively. Excess nitrogen, in the form of ammonia, and other byproducts of the urea cycle, accumulate in the bloodstream, leading to the characteristic features of type I citrullinemia.

Type 1 tyrosinemia typically presents in infancy as failure to thrive and hepatomegaly. The primary effects are progressive liver and kidney dysfunction. The liver disease causes cirrhosis, conjugated hyperbilirubinemia, elevated AFP, hypoglycemia and coagulation abnormalities. This can lead to jaundice, ascites and hemorrhage. There is also an increased risk of hepatocellular carcinoma.

The kidney dysfunction presents as Fanconi syndrome: Renal tubular acidosis, hypophosphatemia and aminoaciduria. Cardiomyopathy, neurologic and dermatologic manifestations are also possible. The urine has an odor of cabbage or rancid butter.

Citrullinemia is an autosomal recessive urea cycle disorder that causes ammonia and other toxic substances to accumulate in the blood. Since the substances also accumulate in the urine, the disorder can also be called citrullinuria.

Two forms of citrullinemia have been described, both having different signs and symptoms, and are caused by mutations in different genes. Citrullinemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of chemical reactions taking place in the liver. These reactions process excess nitrogen, generated when protein is used for energy by the body, to make urea, which is excreted by the kidneys.

Type 1 tyrosinemia, also known as hepatorenal tyrosinemia or tyrosinosis, is the most severe form of tyrosinemia, a buildup of too much of the amino acid tyrosine in the blood and tissues due to an inability to metabolize it. It is caused by a deficiency of the enzyme fumarylacetoacetate hydrolase.

Galactose epimerase deficiency, also known as GALE deficiency, Galactosemia III and UDP-galactose-4-epimerase deficiency, is a rare, autosomal recessive form of galactosemia associated with a deficiency of the enzyme "galactose epimerase".

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.

Type 2 appears when a child is around 18 months of age and in considered milder than Type 1 but still severe. Symptoms include:

- Symptoms similar to Type 1 but milder and progress more slowly.

The most common clinical history in patients with glycogen-storage disease type 0 (GSD-0) is that of an infant or child with symptomatic hypoglycemia or seizures that occur before breakfast or after an inadvertent fast. In affected infants, this event typically begins after they outgrow their nighttime feeds. In children, this event may occur during acute GI illness or periods of poor enteral intake.

Mild hypoglycemic episodes may be clinically unrecognized, or they may cause symptoms such as drowsiness, sweating, lack of attention, or pallor. Uncoordinated eye movements, disorientation, seizures, and coma may accompany severe episodes.

Glycogen-storage disease type 0 affects only the liver. Growth delay may be evident with height and weight percentiles below average. Abdominal examination findings may be normal or reveal only mild hepatomegaly.Signs of acute hypoglycemia may be present, including the following:

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).

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.

A Glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by enzyme deficiencies affecting either glycogen synthesis, glycogen breakdown or glycolysis (glucose breakdown), typically within muscles and/or liver cells.

GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism (genetically defective enzymes) involved in these processes. In livestock, acquired GSD is caused by intoxication with the alkaloid castanospermine.

Glycogen storage disease type 0 is a disease characterized by a deficiency in the glycogen synthase enzyme (GYS). Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified as a glycogen storage disease because it is another defect of glycogen storage and can cause similar problems. There are two isoforms (types) of glycogen synthase enzyme; GYS1 in muscle and GSY2 in liver, each with a corresponding form of the disease. Mutations in the liver isoform (GYS2), causes fasting hypoglycemia, high blood ketones, increased free fatty acids and low levels of alanine and lactate. Conversely, feeding in these patients results in hyperglycemia and hyperlactatemia.

The symptoms of LSD vary, depending on the particular disorder and other variables such as the age of onset, and can be mild to severe. They can include developmental delay, movement disorders, seizures, dementia, deafness, and/or blindness. Some people with LSDhave enlarged livers (hepatomegaly) and enlarged spleens (splenomegaly), pulmonary and cardiac problems, and bones that grow abnormally.

Niemann–Pick Type B involves an enlarged liver and spleen hepatosplenomegaly, growth retardation, and problems with lung function including frequent lung infections. Other signs include blood abnormalities such as abnormal cholesterol and lipid levels, and low numbers of blood cells involved in clotting (platelets). The brain is not affected in Type B and the disease often presents in the pre-teen years.

Niemann–Pick disease, SMPD1-associated refers to two different types of Niemann–Pick disease which are associated with the SMPD1 gene.

There are approximately 1,200 cases of NPA and NPB worldwide with the majority of cases being Type B or an intermediate form.

Descriptions of type E and type F have been published, but they are not well characterized, and are currently classified under type B.

Lysosomal storage diseases (LSDs; ) are a group of about 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective, because of a mutation, the large molecules accumulate within the cell, eventually killing it.

Lysosomal storage disorders are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of lipids, glycoproteins (sugar-containing proteins), or so-called mucopolysaccharides. Individually, LSDs occur with incidences of less than 1:100,000; however, as a group, the incidence is about 1:5,000 - 1:10,000. Most of these disorders are autosomal recessively inherited such as Niemann–Pick disease, type C, but a few are X-linked recessively inherited, such as Fabry disease and Hunter syndrome (MPS II).

The lysosome is commonly referred to as the cell's recycling center because it processes unwanted material into substances that the cell can use. Lysosomes break down this unwanted matter by enzymes, highly specialized proteins essential for survival. Lysosomal disorders are usually triggered when a particular enzyme exists in too small an amount or is missing altogether. When this happens, substances accumulate in the cell. In other words, when the lysosome does not function normally, excess products destined for breakdown and recycling are stored in the cell.

Like other genetic disorders, individuals inherit lysosomal storage diseases from their parents. Although each disorder results from different gene mutations that translate into a deficiency in enzyme activity, they all share a common biochemical characteristic – all lysosomal disorders originate from an abnormal accumulation of substances inside the lysosome.

LSDs affect mostly children and they often die at a young and unpredictable age, many within a few months or years of birth. Many other children die of this disease following years of suffering from various symptoms of their particular disorder.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder which manifests with insulin resistance, absence of subcutaneous fat and muscular hypertrophy. Homozygous or compound heterozygous mutations in four genes are associated with the four subtypes of CGL. The condition appears in early childhood with accelerated linear growth, quick aging of bones, and a large appetite. As the child grows up, acanthosis nigricans (hyperpigmentation and thickening of skin) will begin to present itself throughout the body – mainly in the neck, trunk, and groin. The disorder also has characteristic features like hepatomegaly or an enlarged liver which arises from fatty liver and may lead to cirrhosis, muscle hypertrophy, lack of adipose tissue, splenomegaly, hirsutism (excessive hairiness) and hypertriglyceridemia. Fatty liver and muscle hypertrophy arise from the fact that lipids are instead stored in these areas; whereas in a healthy individual, lipids are distributed more uniformly throughout the body subcutaneously. The absence of adipose tissue where they normally occur causes the body to store fat in the remaining areas. Common cardiovascular problems related to this syndrome are cardiac hypertrophy and arterial hypertension (high blood pressure). This disorder can also cause metabolic syndrome. Most with the disorder also have a prominent umbilicus or umbilical hernia. Commonly, patients will also have acromegaly with enlargement of the hands, feet, and jaw. After puberty, additional symptoms can develop. In women, clitoromegaly and polycystic ovary syndrome can develop. This impairs fertility for women, and only a few documented cases of successful pregnancies in women with CGL exist. However, the fertility of men with the disorder is unaffected.

Congenital generalized lipodystrophy (also known as Berardinelli–Seip syndrome) is an extremely rare autosomal recessive skin condition, characterized by an extreme scarcity of fat in the subcutaneous tissues. It is a type of lipodystophy disorder where the magnitude of fat loss determines the severity of metabolic complications. Only 250 cases of the condition have been reported, and it is estimated that it occurs in 1 in 10 million people worldwide.

Horses with Type 1 PSSM usually appear normal at rest, but show signs of exertional rhabdomyolysis ("tying up") such as shortened stride, stiffness, firm musculature, sweating, pain or reluctance to exercise, when asked to perform light work. While episodes of exertional rhabdomyolysis is one of the most frequent signs associated with affected horses (reported in ~37% of affected animals), other common signs include gait abnormalities, shifting lameness, muscle weakness that may result in an inability to rise, colic-like pain, and muscle fasciculation, atrophy, and/or stiffness (most commonly seen in the semimembranosis, semitendinosis, and longissimus muscles).

These clinical signs usually first become apparent when the horse is placed into training as a young animal; however, affected horses will show histological changes consistent with muscle damage at one month of age, and may also show elevations in creatine kinase (CK), an enzyme that elevates with muscle damage. Concurrent illness, such as respiratory or gastrointestinal infection, can lead to elevations in CK and potentially life-threatening rhabdomyolysis, even without exercise. Horses with PSSM often have a persistently elevated CK at rest, which differentiates the disease from recurrent exertional rhabdomyolysis, in which horses have normal CK concentrations between episodes.

The onset of the disease is usually before age 2, but patients have been diagnosed with PFIC even into adolescence. Of the three entities, PFIC-3 usually presents earliest. Patients usually present in early childhood with cholestasis, jaundice, and failure to thrive. Intense pruritus is characteristic; in patients who present in adolescence, it has been linked with suicide. Patients may have fat malabsorption, leading to fat soluble vitamin deficiency, and complications, including osteopenia.

Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions caused by defects in biliary epithelial transporters. The clinical presentation usually occurs first in childhood with progressive cholestasis. This usually leads to failure to thrive, cirrhosis, and the need for liver transplantation.