Males

In males the symptoms of Danon Disease are more severe. Features of Danon Disease in males are:

- An early age of onset of muscle weakness and heart disease (onset in childhood or adolescence)

- Some learning problems or intellectual disability can be present

- Muscle weakness can be severe and can affect endurance and the ability to walk

- Heart disease (cardiomyopathy) can be severe and can lead to a need for medications. It usually progress to heart failure, commonly complicated by atrial fibrillation and embolic strokes with severe neurological disability, leading to death unless heart transplant is performed.

- Cardiac conduction abnormalities can occur. Wolff-Parkinson-White syndrome is a common conduction pattern in Danon disease.

- Symptoms are usually gradually progressive

- Some individuals may have visual disturbances, and/or retinal pigment abnormalities

- Danon Disease is rare and unfamiliar to most physicians. It can be mistaken for other forms of heart disease and/or muscular dystrophies, including Pompe disease.

Females

In females the symptoms of Danon Disease are less severe. Common symptoms of Danon Disease in females are:

- A later age of onset of symptoms. Many females will not have obvious symptoms until late adolescence or even adulthood.

- Learning problems and intellectual disability are usually ABSENT

- Muscle weakness is often absent or subtle. Some females will tire easily with exercise

- Cardiomyopathy) is often absent in childhood. Some women will develop this in adulthood. Cardiomyopathy can be associated with atrial fibrillation and embolic strokes.

- Cardiac conduction abnormalities can occur. Wolff-Parkinson-White syndrome is a common conduction pattern in Danon disease.

- Symptoms in females progress more slowly than in males.

- Some females may have visual disturbances, and/or retinal pigment abnormalities

- Danon Disease is rare and unfamiliar to most physicians. The milder and more subtle symptoms in females can make it more difficult to diagnose females with Danon Disease

Danon disease (or glycogen storage disease Type IIb) is a metabolic disorder.Danon disease is an X-linked lysosomal and glycogen storage disorder associated with hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability.

Infants with Krabbe disease are normal at birth. Symptoms begin between the ages of 3 and 6 months with irritability, fevers, limb stiffness, seizures, feeding difficulties, vomiting, and slowing of mental and motor development. In the first stages of the disease, doctors often mistake the symptoms for those of cerebral palsy. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy, optic nerve enlargement, blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur. Juvenile- and adult-onset cases of Krabbe disease also occur, which have similar symptoms but slower progression.

Individuals with Refsum disease present with neurologic damage, cerebellar degeneration, and peripheral neuropathy. Onset is most commonly in childhood/adolescence with a progressive course, although periods of stagnation or remission occur. Symptoms also include ataxia, scaly skin (ichthyosis), difficulty hearing, and eye problems including retinitis pigmentosa, cataracts, and night blindness. In 80% of patients diagnosed with Refsum disease, sensorineural hearing loss has been reported. This is hearing loss as the result of damage to the inner ear or the nerve connected to ear to the brain.

There are three main types of the disease each with its own distinctive symptoms.

Type I infantile form, infants will develop normally until about a year old. At this time, the affected infant will begin to lose previously acquired skills involving the coordination of physical and mental behaviors. Additional neurological and neuromuscular symptoms such as diminished muscle tone, weakness, involuntary rapid eye movements, vision loss, and seizures may become present. With time, the symptoms worsen and children affected with this disorder will experience a decreased ability to move certain muscles due to muscle rigidity. The ability to respond to external stimuli will also decrease. Other symptoms include neuroaxonal dystrophy from birth, discoloration of skin, Telangiectasia or widening of blood vessels.

Type II adult form, symptoms are milder and may not appear until the individual is in his or her 30s. Angiokeratomas, an increased coarsening of facial features, and mild intellectual impairment are likely symptoms.

Type III is considered an intermediate disorder. Symptoms vary and can include to be more severe with seizures and mental retardation, or less severe with delayed speech, a mild autistic like presentation, and/or behavioral problems.

Symptoms are typically first experienced in early childhood and can be very difficult to understand; the rarity of Fabry disease to many clinicians sometimes leads to misdiagnoses. Manifestations of the disease usually increase in number and severity as an individual ages.

Sandhoff disease symptoms are clinically indeterminable from Tay–Sachs disease. The classic infantile form of the disease has the most severe symptoms and is incredibly hard to diagnose at this early age. The first signs of symptoms begin before 6 months of age and the parents’ notice when the child begins regressing in their development. If the children had the ability to sit up by themselves or crawl they will lose this ability. This is caused by a slow deterioration of the muscles in the child’s body from the buildup of GM2 gangliosides. Since the body is unable to create the enzymes it needs within the central nervous system it is unable to attach to these gangliosides to break them apart and make them non-toxic. With this buildup there are several symptoms that begin to appear such as muscle/motor weakness, sharp reaction to loud noises, blindness, deafness, inability to react to stimulants, respiratory problems and infections, mental retardation, seizures, cherry red spots in the retina, enlarged liver and spleen (hepatosplenomegaly), pneumonia, or bronchopneumonia.

The other two forms of Sandhoff disease have similar symptoms but to a lesser extent. Adult and juvenile forms of Sandhoff disease are more rare than the infantile form. In these cases victims suffer cognitive impairment (retardation) and a loss of muscle coordination that impairs and eventually destroys their ability to walk; the characteristic red spots in the retina also develop. The adult form of the disease, however, is sometimes milder, and may only lead to muscle weakness that impairs walking or the ability to get out of bed.

Full body or localized pain to the extremities (known as acroparesthesia) or gastrointestinal (GI) tract is common in patients with Fabry disease. This acroparesthesia is believed to be related to the damage of peripheral nerve fibers that transmit pain. GI tract pain is likely caused by accumulation of lipids in the small vasculature of the GI tract which obstructs blood flow and causes pain.

Disease onset is typically in early infancy but may occur later in life. Children who have the classic form of Farber disease develop symptoms within the first few weeks of life. These symptoms may include moderately impaired mental ability and problems with swallowing. The liver, heart and kidneys may also be affected. Other symptoms may include vomiting, arthritis, swollen lymph nodes, swollen joints, joint contractures (chronic shortening of muscles or tendons around joints), hoarseness and xanthomas which thicken around joints as the disease progresses. Patients with breathing difficulty may require a breathing tube.

Tay–Sachs disease is typically first noticed in infants around 6 months old displaying an abnormally strong response to sudden noises or other stimulus, known as the "startle response," because they are startled. There may also be listlessness or muscle stiffness (hypertonia). The disease is classified into several forms, which are differentiated based on the onset age of neurological symptoms.

- Infantile Tay–Sachs disease. Infants with Tay–Sachs disease appear to develop normally for the first six months after birth. Then, as neurons become distended with gangliosides, a relentless deterioration of mental and physical abilities begins. The child may become blind, deaf, unable to swallow, atrophied, and paralytic. Death usually occurs before the age of four.

- Juvenile Tay–Sachs disease. Juvenile Tay–Sachs disease is rarer than other forms of Tay–Sachs, and usually is initially seen in children between two and ten years old. People with Tay–Sachs disease develop cognitive and motor skill deterioration, dysarthria, dysphagia, ataxia, and spasticity. Death usually occurs between the age of five to fifteen years.

- Adult/Late-Onset Tay–Sachs disease. A rare form of this disease, known as Adult-Onset or Late-Onset Tay–Sachs disease, usually has its first symptoms during the 30s or 40s. In contrast to the other forms, late-onset Tay–Sachs disease is usually not fatal as the effects can stop progressing. It is frequently misdiagnosed. It is characterized by unsteadiness of gait and progressive neurological deterioration. Symptoms of late-onset Tay–Sachs – which typically begin to be seen in adolescence or early adulthood – include speech and swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline, and psychiatric illness, particularly a schizophrenia-like psychosis. People with late-onset Tay–Sachs may become full-time wheelchair users in adulthood.

Until the 1970s and 1980s, when the disease's molecular genetics became known, the juvenile and adult forms of the disease were not always recognized as variants of Tay–Sachs disease. Post-infantile Tay–Sachs was often misdiagnosed as another neurological disorder, such as Friedreich's ataxia.

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.

Early signs and symptoms of the disorder usually appear around ages 2–10, with gradual onset of vision problems, or seizures. Early signs may be subtle personality and behavior changes, slow learning or regression, repetitive speech or echolalia, clumsiness, or stumbling. Slowing head growth in the infantile form, poor circulation in lower extremities (legs and feet), decreased body fat and muscle mass, curvature of the spine, hyperventilation and/or breath-holding spells, teeth grinding, and constipation may occur.

Over time, affected children suffer mental impairment, worsening seizures, and progressive loss of sight, speech, and motor skills. Batten disease is a terminal disease; life expectancy varies depending on the type or variation.

Females with juvenile Batten disease show first symptoms a year later than males, but on average die a year sooner.

Krabbe disease (KD) (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare and often fatal lysosomal storage disease which results in progressive damage to the nervous system. KD involves dysfunctional metabolism of sphingolipids and is inherited in an autosomal recessive pattern. The disease is named after the Danish neurologist Knud Krabbe (1885–1965).

New York, Missouri and Kentucky include Krabbe in the newborn screening panel.

Refsum disease, also known as classic or adult Refsum disease, heredopathia atactica polyneuritiformis, phytanic acid oxidase deficiency and phytanic acid storage disease, is an autosomal recessive neurological disease that results from the over-accumulation of phytanic acid in cells and tissues. It is one of several disorders named after Norwegian neurologist Sigvald Bernhard Refsum (1907–1991). Refsum disease typically is adolescent onset and is diagnosed by above average levels of phytanic acid. Humans obtain the necessary phytanic acid primarily through diet. It is still unclear what function phytanic acid plays physiologically in humans, but has been found to regulate fatty acid metabolism in the liver of mice.

There are three types of Sandhoff disease: classic infantile, juvenile, and adult late onset. Each form is classified by the severity of the symptoms as well as the age at which the patient shows these symptoms.

- Classic infantile form of the disease is classified by the development of symptoms anywhere from 2 months to 9 months of age. It is the most severe of all of the forms and will lead to death before the patient reaches the age of three. This is the most common and severe form of Sandhoff disease. Infants with this disorder typically appear normal until the age of 3 to 6 months, when development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. As the disease progresses, infants develop seizures, vision and hearing loss, dementia, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Some infants with Sandhoff disease may have enlarged organs (organomegaly) or bone abnormalities. Children with the severe form of this disorder usually live only into early childhood.

- Juvenile form of the disease shows symptoms starting at age 3 ranging to age 10 and, although the child usually dies by the time they are 15, it is possible for them to live longer if they are under constant care. Symptoms include autism, ataxia, motor skills regression, spacticity, and learning disorders.

- Adult onset form of the disease is classified by its occurrence in older individuals and has an effect on the motor function of these individuals. It is not yet known if Sandhoff disease will cause these individuals to have a decrease in their life span.

Juvenile and adult onset forms of Sandhoff disease are very rare. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form of Sandhoff disease. As in the infantile form, mental abilities and coordination are affected. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Sandhoff disease.

Schindler disease, also known as Kanzaki disease and alpha-N-acetylgalactosaminidase deficiency is a rare disease found in humans. This lysosomal storage disorder is caused by a deficiency in the enzyme alpha-NAGA (alpha-N-acetylgalactosaminidase), attributable to mutations in the NAGA gene on chromosome 22, which leads to excessive lysosomal accumulation of glycoproteins. A deficiency of the alpha-NAGA enzyme leads to an accumulation of glycosphingolipids throughout the body. This accumulation of sugars gives rise to the clinical features associated with this disorder. Schindler disease is an autosomal recessive disorder, meaning that one must inherit an abnormal allele from both parents in order to have the disease.

Most children with Farber disease die by age 2, usually from lung disease. In one of the most severe forms of the disease, an enlarged liver and spleen (hepatosplenomegaly) can be diagnosed soon after birth. Children born with this form of the disease usually die within 6 months.

Batten disease is a fatal disease of the nervous system that typically begins in childhood. Onset of symptoms is usually between 5 and 10 years of age. Often it is autosomal recessive. It is the most common form of a group of disorders called the neuronal ceroid lipofuscinoses (NCLs).

Although Batten disease is usually regarded as the juvenile form of NCL (or "type 3"), some physicians use the term Batten disease to describe all forms of NCL. Historically, the NCLs were classified by age of disease onset as infantile NCL (INCL), late infantile NCL (LINCL), juvenile NCL (JNCL) or adult NCL (ANCL). At least 20 genes have been identified in association with Batten disease, but juvenile NCL, the most prevalent form of Batten disease, has been linked to mutations in the "CLN3" gene.

It was first described in 1903.

Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common type, known as infantile Tay–Sachs disease, becomes apparent around three to six months of age with the baby losing the ability to turn over, sit, or crawl. This is then followed by seizures, hearing loss, and inability to move. Death usually occurs in early childhood. Less commonly the disease may occur in later childhood or adulthood. These forms are generally milder in nature.

Tay–Sachs disease is caused by a genetic mutation in the "HEXA" genes on chromosome 15. It is inherited from a person's parents in an autosomal recessive manner. The mutation results in problems with an enzyme called beta-hexosaminidase A which results in the buildup of the molecule GM2 ganglioside within cells, leading to toxicity. Diagnosis is by measuring the blood hexosaminidase A level or genetic testing. It is a type of sphingolipidoses.

The treatment of Tay–Sachs disease is supportive in nature. This may involve multiple specialities as well as psychosocial support for the family. The disease is rare in the general population. In Ashkenazi Jews, French Canadians of southeastern Quebec, and Cajuns of southern Louisiana, the condition is more common. Approximately 1 in 3,600 Ashkenazi Jews at birth are affected.

The disease is named after Waren Tay, who in 1881 first described a symptomatic red spot on the retina of the eye; and Bernard Sachs, who described in 1887 the cellular changes and noted an increased rate of disease in Ashkenazi Jews. Carriers of a single Tay–Sachs allele are typically normal. It has been hypothesized that being a carrier may confer protection from another condition such as tuberculosis, explaining the persistence of the allele in certain populations. Researchers are looking at gene therapy or enzyme replacement therapy as possible treatments.

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.

Other lipid storage disorders that are generally not classified as sphingolipidoses include fucosidosis, Schindler disease and Wolman disease.

A lipid storage disorder (or lipidosis) can be any one of a group of inherited metabolic disorders in which harmful amounts of fats or lipids accumulate in some of the body’s cells and tissues. People with these disorders either do not produce enough of one of the enzymes needed to metabolize and break down lipids or they produce enzymes that do not work properly. Over time, this excessive storage of fats can cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system, liver, spleen and bone marrow.

Inside cells under normal conditions, lysosomes convert, or metabolize, lipids and proteins into smaller components to provide energy for the body.

Urbach–Wiethe disease is characterized by both neurological and dermatological symptoms.

Although the dermatological changes are the most obvious symptoms of Urbach–Wiethe disease, many patients also have neurological symptoms. About 50–75% of the diagnosed cases of Urbach–Wiethe disease also show bilateral symmetrical calcifications on the medial temporal lobes. These calcifications often affect the amygdala and the periamygdaloid gyri. The amygdala is thought to be involved in processing biologically relevant stimuli and in emotional long term memory, particularly those associated with fear, and both PET and MRI scans have shown a correlation between amygdala activation and episodic memory for strongly emotional stimuli. Therefore, Urbach–Wiethe disease patients with calcifications and lesions in these regions may suffer impairments in these systems. These calcifications are the result of a buildup of calcium deposits in the blood vessels within this brain region. Over time, these vessels harden and the tissue they are a part of dies, causing lesions. The amount of calcification is often related to disease duration. The true prevalence of these calcifications is difficult to accurately state as not all patients undergo brain imaging. Some patients also exhibit epilepsy and neuropsychiatric abnormalities. Epilepsy symptoms could begin with light anxiety attacks and it can be controlled with "Epilum" (Epilepsy Medicine) Other patients present with symptoms similar to schizophrenia while some suffer from mood, anxiety, and psychotic disorders.

Sphingolipidoses (singular "sphingolipidosis") are a class of lipid storage disorders relating to sphingolipid metabolism. The main members of this group are Niemann–Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay–Sachs disease and metachromatic leukodystrophy. They are generally inherited in an autosomal recessive fashion, but notably Fabry disease is X-linked recessive. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000, but substantially more in certain populations such as Ashkenazi Jews. Enzyme replacement therapy is available to treat mainly Fabry disease and Gaucher disease, and people with these types of sphingolipidoses may live well into adulthood. The other types are generally fatal by age 1 to 5 years for infantile forms, but progression may be mild for juvenile- or adult-onset forms.