Symptoms of early infantile GM1 (the most severe subtype, with onset shortly after birth) may include neurodegeneration, seizures, liver enlargement (hepatomegaly), spleen enlargement (splenomegaly), coarsening of facial features, skeletal irregularities, joint stiffness, distended abdomen, muscle weakness, exaggerated startle response to sound, and problems with gait.

About half of affected patients develop cherry-red spots in the eye.

Children may be deaf and blind by age 1 and often die by age 3 from cardiac complications or pneumonia.

- Autosomal recessive disorder; beta-galactosidase deficiency; neuronal storage of GM1 ganglioside and visceral storage of galactosyl oligosaccharides and keratan sulfate.

- Early psychomotor deterioration: decreased activity and lethargy in the first weeks; never sit; feeding problems - failure to thrive; visual failure (nystagmus noted) by 6 months; initial hypotonia; later spasticity with pyramidal signs; secondary microcephaly develops; decerebrate rigidity by 1 year and death by age 1–2 years (due to pneumonia and respiratory failure); some have hyperacusis.

- Macular cherry-red spots in 50% by 6–10 months; corneal opacities in some

- Facial dysmorphology: frontal bossing, wide nasal bridge, facial edema (puffy eyelids); peripheral edema, epicanthus, long upper lip, microretrognathia, gingival hypertrophy (thick alveolar ridges), macroglossia

- Hepatomegaly by 6 months and splenomegaly later; some have cardiac failure

- Skeletal deformities: flexion contractures noted by 3 months; early subperiosteal bone formation (may be present at birth); diaphyseal widening later; demineralization; thoracolumbar vertebral hypoplasia and beaking at age 3–6 months; kyphoscoliosis. *Dysostosis multiplex (as in the mucopolysaccharidoses)

- 10–80% of peripheral lymphocytes are vacuolated; foamy histiocytes in bone marrow; visceral mucopolysaccharide storage similar to that in Hurler disease; GM1 storage in cerebral gray matter is 10-fold elevated (20–50-fold increased in viscera)

- Galactose-containing oligosacchariduria and moderate keratan sulfaturia

- Morquio disease Type B: Mutations with higher residual beta-galactosidase activity for the GM1 substrate than for keratan sulfate and other galactose-containing oligosaccharides have minimal neurologic involvement but severe dysostosis resembling Morquio disease type A (Mucopolysaccharidosis type 4).

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.

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.

Onset of late infantile GM1 is typically between ages 1 and 3 years.

Neurological symptoms include ataxia, seizures, dementia, and difficulties with speech.

This disorder usually appears within the first year of life. The signs and symptoms of HMG-CoA lyase deficiency include vomiting, dehydration, lethargy, convulsions, and coma. When episodes occur in an infant or child, blood sugar becomes extremely low (hypoglycemia), and harmful compounds can build up and cause the blood to become too acidic (metabolic acidosis). These episodes are often triggered by an infection, fasting, strenuous exercise, or sometimes other types of stress.

3-Hydroxy-3-methylglutaryl-CoA lyase deficiency also referred to as HMG-CoA lyase deficiency or Hydroxymethylglutaric aciduria, is an uncommon inherited disorder in which the body cannot properly process the amino acid leucine. Additionally, the disorder prevents the body from making ketones, which are used for energy during fasting.

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.

3-Methylcrotonyl-CoA carboxylase deficiency (3MCC deficiency), also known as 3-Methylcrotonylglycinuria or BMCC deficiency is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have inadequate levels of an enzyme that helps break down proteins containing the amino acid leucine. This condition affects an estimated 1 in 50,000 individuals worldwide.

3-Methylglutaconic aciduria (MGA) is any of at least five metabolic disorders that impair the body's ability to make energy in the mitochondria. As a result of this impairment, 3-methylglutaconic acid and 3-methylglutaric acid build up and can be detected in the urine.

3-Methylglutaconic acid is an organic acid. The double carboxylic acid functions are the principal cause of the strength of this acid. 3-methylglutaconic acid can be detected by the presence of the acid function and the double connection that involves reactivity with some specific substances.

There are five known subgroups of MGA; MGA type I,II,III,IV & V.

The characteristic features of 3-methylglutaconic aciduria type I include speech delay, delayed development of both mental and motor skills (psychomotor delay), elevated levels of acid in the blood and tissues (metabolic acidosis), abnormal muscle tone (dystonia), and spasms and weakness affecting the arms and legs (spastic quadriparesis). Fewer than 20 cases of 3-methylglutaconic aciduria type I have been reported.

Barth syndrome is a common name for 3-methylglutaconic aciduria type II. The main features of Barth syndrome include a weakened and enlarged heart (dilated cardiomyopathy), recurrent infections due to low numbers of white blood cells (neutropenia), skeletal problems, and delayed growth. The incidence of 3-methylglutaconic aciduria type II is approximately 1 in 200,000 male infants.

Costeff optic atrophy syndrome is another name for 3-methylglutaconic aciduria type III. This disorder is characterized mainly by the degeneration of the optic nerves, which carry information from the eyes to the brain. Sometimes other nervous system problems occur, such as an inability to maintain posture, poor muscle tone, the development of certain involuntary movements (extrapyramidal dysfunction), and a general decrease in brain function (cognitive deficit). The incidence of 3-methylglutaconic aciduria type III is about 1 in 10,000 newborns in the Iraqi Jewish population. This disorder is extremely rare in all other populations.

The signs and symptoms of 3-methylglutaconic aciduria type IV are variable and overlap with types I-III. The incidence of 3-methylglutaconic aciduria type IV is unknown.

Typically, initial signs and symptoms of this disorder occur during infancy or early childhood and can include poor appetite, vomiting, diarrhea, lethargy, hypoglycemia, hypotonia, liver problems, and abnormally high levels of hyperinsulinism. Insulin controls the amount of sugar that moves from the blood into cells for conversion to energy. Individuals with 3-hydroxyacyl-coenzyme A dehydrogenase deficiency are also at risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden unexpected death.

Problems related to 3-hydroxyacyl-coenzyme A dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop 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.

Succinyl-CoA:3-oxoacid CoA transferase deficiency (SCOT deficiency) is an inborn error of ketone body utilization. Succinyl-CoA:3-oxoacid CoA transferase catalyzes the transfer of coenzyme A from succinyl-coenzyme A to acetoacetate. It can be caused by mutation in the "OXCT1" gene.

First described in 1972, more than 30 people have been reported in the medical literature with this inborn error of metabolism. They experience attacks of ketoacidosis during illness, and even when unwell may have elevated levels of ketone bodies in blood and urine (ketonemia and ketonuria, respectively). Not all people with SCOT deficiency have persistent ketonemia and ketonuria, particularly those with milder defects of enzyme activity.

3-Hydroxyisobutyric aciduria is a disorder of valine metabolism characterised by urinary excretion of 3-Hydroxyisobutyric acid.

Congenital dyserythropoietic anemia type II (CDA II), or hereditary erythroblastic multinuclearity with positive acidified serum lysis test (HEMPAS) is a rare genetic anemia in humans characterized by hereditary erythroblastic multinuclearity with positive acidified serum lysis test.

3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADH deficiency) is a rare condition that prevents the body from converting certain fats to energy, particularly during fasting. Normally, through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to metabolize fats and convert them to energy. People with 3-hydroxyacyl-coenzyme A dehydrogenase deficiency have inadequate levels of an enzyme required for a step that metabolizes groups of fats called medium chain fatty acids and short chain fatty acids; for this reason this disorder is sometimes called medium- and short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (M/SCHAD) deficiency.

The anemia associated with CDA type II can range from mild to severe, and most affected individuals have jaundice, hepatosplenomegaly, and the formation of hard deposits in the gallbladder called bilirubin gallstones. This form of the disorder is usually diagnosed in adolescence or early adulthood. An abnormal buildup of iron typically occurs after age 20, leading to complications including heart disease, diabetes, and cirrhosis.

Many of the physical features associated with the disorder are congenital. Characteristic craniofacial abnormalities typically include a long, narrow head that is disproportionate to the body size, a broad and prominent forehead, and a triangular-shaped face with a hypoplastic midface, pointed chin, prominent mouth, fleshy tipped upturned nose, large ears, and full lips. The teeth may be abnormally crowded together in some affected individuals.

Skeletal anomalies aren't present at birth but develop in the individual and include delayed bone maturation, slender long tubular bones, and tall vertebral bodies. Joint hyper-mobility and increased risk of hip dislocation has been presented in individuals. Abnormal spinal curvature, either kyhoscholiosis or hyperlordosis, causing back pain can also be experienced from this disorder.

Janus kinase 3 deficiency or JAK3 deficiency is a defect in the body's cytokine receptors and their signaling. JAK3 encodes Janus kinase 3, a tyrosine kinase that belongs to the Janus family. JAK3 functions in signal transduction and interacts with members of the STAT (signal transduction and activators of transcription) family. The cause of JAK3 deficiency. The deficiency causes the near absence of T lymphocytes and Natural killer cells; and normal or elevated B lymphocytes due to an autosomal recessive variant of severe combined immunodeficiency (SCID).

The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infections or developmental delay as a result of infection. Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a "primary" immunodeficiency, the cause of the immune deficiency must not be secondary in nature (i.e., caused by other disease, drug treatment, or environmental exposure to toxins). Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 100 recognized PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, autoinflammatory disorders, tumors, and disorders of various organs. There are currently no cures for these conditions; treatment is palliative and consists of managing infections and boosting the immune system.

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.

The most common presentation of Milroy Disease is bilateral lower extremity lymphedema, and may also be accompanied by hydrocele.

Acrocallosal syndrome (also known as ACLS) is a rare autosomal recessive syndrome characterized by corpus callosum agenesis, polydactyly, multiple dysmorphic features, motor and mental retardation, and other symptoms. The syndrome was first described by Albert Schinzel in 1979.

It is associated with "GLI3".