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.

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.

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.

The classic characterization of the group of neurodegenerative, lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs) is through the progressive, permanent loss of motor and psychological ability with a severe intracellular accumulation of lipofuscins, with the United States and northern European populations having slightly higher frequency with an occurrence of 1 in 10,000. There are four classic diagnoses that have received the most attention from researchers and the medical field, differentiated from one another by age of symptomatic onset, duration, early-onset manifestations such as blindness or seizures, and the forms which lipofuscin accumulation takes.

In the early infantile variant of NCL (also called INCL or Santavuori-Haltia), probands appear normal at birth, but early visual loss leading to complete retinal blindness by the age of 2 years is the first indicator of the disease; by 3 years of age a vegetative state is reached and by 4 years isoelectric encephalograms confirm brain death. Late infantile variant usually manifests between 2 and 4 years of age with seizures and deterioration of vision. The maximum age before death for late infantile variant is 10–12 years. Juvenile NCL (JNCL, Batten Disease, or Spielmeyer-Vogt), with a prevalence of 1 in 100,000, usually arises between 4 and 10 years of age; the first symptoms include considerable vision loss due to retinal dystrophy, with seizures, psychological degeneration, and eventual death in the mid- to late-20s or 30s ensuing. Adult variant NCL (ANCL or Kuf’s Disease) is less understood and generally manifests milder symptoms; however, while symptoms typically appear around 30 years of age, death usually occurs ten years later.

All the mutations that have been associated with this disease have been linked to genes involved with the neural synapses metabolism – most commonly with the reuse of vesicle proteins.

Jansky–Bielschowsky disease is an extremely rare autosomal recessive genetic disorder that is part of the neuronal ceroid lipofuscinosis (NCL) family of neurodegenerative disorders. It is caused by the accumulation of lipopigments in the body due to a deficiency in tripeptidyl peptidase I as a result of a mutation in the TPP1 gene. Symptoms appear between ages 2 and 4 and consist of typical neurodegenerative complications: loss of muscle function (ataxia), drug resistant seizures (epilepsy), apraxia, development of muscle twitches (myoclonus), and vision impairment. This late-infantile form of the disease progresses rapidly once symptoms are onset and ends in death between age 8 and teens. The prevalence of Jansky–Bielschowsky disease is unknown, however NCL collectively affects an estimated 1 in 100,000 individuals worldwide. Jansky–Bielschowsky disease is also known as: late-infantile Batten disease, LINCL, or neuronal ceroid lipofuscinosis.

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.

Neuronal ceroid lipofuscinosis (NCL) is the general name for a family of at least eight genetically separate neurodegenerative disorders that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues. These lipopigments are made up of fats and proteins. Their name comes from the word stem "lipo-", which is a variation on "lipid" or "fat", and from the term "pigment", used because the substances take on a greenish-yellow color when viewed under an ultraviolet light microscope. These lipofuscin materials build up in neuronal cells and many organs, including the liver, spleen, myocardium, and kidneys.

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.

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.

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.

Diagnosis of Jansky–Bielschowsky disease is increasingly based on assay of enzyme activity and molecular genetic testing. Thirteen pathogenic candidate genes—PPT1, TPP1, CLN3, CLN5, CLN6, MFSD8, CLN8, CTSD, DNAJC5, CTSF, ATP13A2 GRN, KCTD7—are associated with the development of the disease. Patients with Jansky–Bielschowsky disease typically have up to 50% reduced lysosomal enzymes, and thus an enzyme activity assay is a quick and easy diagnostic test.

Vision impairment is an early symptom of Jansky–Bielschowsky disease, and so an eye exam is another common diagnostic tool. During the eye exam, loss of cells within the eye would indicate the presence of the disease however more tests are needed for a complete diagnosis.

Other common diagnostic tests include:

- Blood or urine test: Elevated levels of the chemical dolichol found in the urine is typical of individuals with the disease, as well as the presence of vacuolated lymphocytes in the blood.

- Skin or tissue sampling: Microscopy of skin could be used to observe lipopigment aggregation.

- CT scan or MRI: Visualization of the brain would be able to detect areas of cerebral atrophy.

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.

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.

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.

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

Chorea-acanthocytosis (ChAc, also called Choreoacanthocytosis), is a rare hereditary disease caused by a mutation of the gene that directs structural proteins in red blood cells. It belongs to a group of four diseases characterized under the name Neuroacanthocytosis. When a patient's blood is viewed under a microscope, some of the red blood cells appear thorny. These thorny cells are called acanthocytes.

Other effects of the disease may include epilepsy, behaviour changes, muscle degeneration, and neuronal degradation similar to Huntington's Disease. The average age of onset of symptoms is 35 years. The disease is incurable and inevitably leads to premature death.

Some more information about Chorea-acanthocytosis is that it is a very complex autosomal recessive adult-onset neurodegenerative disorder. It often shows itself as a mixed movement disorder, in which chorea, tics, dystonia and even parkinsonism may appear as a symptom.

This disease is also characterized by the presence of a few different movement disorders including chorea, dystonia etc.

Chorea-acanthocytosis is considered an autosomal recessive disorder, although a few cases with autosomal dominant inheritance have been noted.

There are multiple symptoms that can help this disease to be diagnosed, this disease is marked by the presence of acanthocytes in blood (these acanthocytes can sometimes be absent or even make a late appearance in the course of the disease.) and neurodegeneration causing a choreiform movement disorder.

Another one of them would be that this disease should be considered in patients who have elevated levels of acanthocytes in a peripheral blood film.

The serum creatine kinase is often elevated in the body of the people who are affected by this disease.

People afflicted by this disease also experience a loss of neurons. Loss of neurons is a hallmark of neurodegenerative diseases. Due to the generally non-regenerative nature of neuronal cells in the adult central nervous system, this results in an irreversible and fatal process of neurodegeneration. There is also the presence of several movement related disorders including chorea, dystonia and bradykinesia, one of the more incapacitating ones includes Truncal spasms.

It is associated with LAMP2. The status of this condition as a GSD has been disputed.

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.

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.

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.

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.

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.

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

The majority of patients is initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis. In some families where the disease-causing mutations are known and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders.