Adult polyglucosan body disease is a condition that affects the nervous system. People with this condition have problems walking due to reduced sensation in their legs (peripheral neuropathy) and progressive muscle weakness and stiffness (spasticity). Damage to the nerves that control bladder function, a condition called neurogenic bladder, causes affected individuals to have progressive difficulty controlling the flow of urine. About half of people with adult polyglucosan body disease experience a decline in intellectual function (dementia). Most people with the condition first go to the doctor due to the bladder issues.

People with adult polyglucosan body disease typically first experience signs and symptoms related to the condition between ages 30 and 60.

The onset of this disease is usually noticed in childhood, but often not diagnosed until the third or fourth decade of life. Symptoms include exercise intolerance with muscle pain, early fatigue, painful cramps, and myoglobin in the urine (often provoked by a bout of exercise). Myoglobinuria may result from the breakdown of skeletal muscle known as rhabdomyolysis, a condition in which muscle cells breakdown, sending their contents into the bloodstream.

Patients may exhibit a “second wind” phenomenon. This is characterized by the patient’s better tolerance for aerobic exercise such as walking and cycling after approximately 10 minutes. This is attributed to the combination of increased blood flow and the ability of the body to find alternative sources of energy, like fatty acids and proteins. In the long term, patients may exhibit renal failure due to the myoglobinuria, and with age, patients may exhibit progressively increasing weakness and substantial muscle loss.

Patients may present at emergency rooms with severe fixed contractures of the muscles and often severe pain. These require urgent assessment for rhabdomyolysis as in about 30% of cases this leads to acute renal failure. Left untreated this can be life-threatening. In a small number of cases compartment syndrome has developed, requiring prompt surgical referral.

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.

This form differs from the infantile principally in the relative lack of cardiac involvement. The onset is more insidious and has a slower progression. Cardiac involvement may occur but is milder than in the infantile form. Skeletal involvement is more prominent with a predilection for the lower limbs.

Late onset features include impaired cough, recurrent chest infections, hypotonia, progressive muscle weakness, delayed motor milestones, difficulty swallowing or chewing and reduced vital capacity.

Prognosis depends on the age of onset on symptoms with a better prognosis being associated with later onset disease.

Adult polyglucosan body disease (APBD) is an orphan disease and a glycogen storage disorder that is caused by an inborn error of metabolism. Symptoms can emerge any time after the age of 30; early symptoms include trouble controlling urination, trouble walking, and lack of sensation in the legs. People eventually develop dementia.

A person inherits loss-of-function mutations in the "GBE1" gene from each parent, and the lack of glycogen branching enzyme (the protein encoded by "GNE1") leads to buildup of unbranched glycogen in cells, which harms neurons more than other kinds of cells.

Most people first go to the doctor due to trouble with urination. The condition is diagnosed by gathering symptoms, a neurological examination, laboratory tests including genetic testing, and medical imaging. As of 2015 there was no cure or treatment, but the symptoms could be managed. People diagnosed with APBD can live a long time after diagnosis, but will probably die earlier than people without the condition.

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 infantile form usually comes to medical attention within the first few months of life. The usual presenting features are cardiomegaly (92%), hypotonia (88%), cardiomyopathy (88%), respiratory distress (78%), muscle weakness (63%), feeding difficulties (57%) and failure to thrive (50%).

The main clinical findings include floppy baby appearance, delayed motor milestones and feeding difficulties. Moderate hepatomegaly may be present. Facial features include macroglossia, wide open mouth, wide open eyes, nasal flaring (due to respiratory distress), and poor facial muscle tone. Cardiopulmonary involvement is manifested by increased respiratory rate, use of accessory muscles for respiration, recurrent chest infections, decreased air entry in the left lower zone (due to cardiomegaly), arrhythmias and evidence of heart failure.

Median age at death in untreated cases is 8.7 months and is usually due to cardiorespiratory failure.

Mucolipidosis II (ML II) is a particularly severe form of ML that has a significant resemblance to another mucopolysaccharidoses called Hurler syndrome. Generally only laboratory testing can distinguish the two as the presentation is so similar. There are high plasma levels of lysosomal enzymes and are often fatal in childhood. Typically, by the age of 6 months, failure to thrive and developmental delays are obvious symptoms of this disorder. Some physical signs, such as abnormal skeletal development, coarse facial features, and restricted joint movement, may be present at birth. Children with ML II usually have enlargement of certain organs, such as the liver (hepatomegaly) or spleen (splenomegaly), and sometimes even the heart valves. Affected children often have stiff claw-shaped hands and fail to grow and develop in the first months of life. Delays in the development of their motor skills are usually more pronounced than delays in their cognitive (mental processing) skills. Children with ML II eventually develop a clouding on the cornea of their eyes and, because of their lack of growth, develop short-trunk dwarfism (underdeveloped trunk). These young patients are often plagued by recurrent respiratory tract infections, including pneumonia, otitis media (middle ear infections), bronchitis and carpal tunnel syndrome. Children with ML II generally die before their seventh year of life, often as a result of congestive heart failure or recurrent respiratory tract infections.

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.

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).

The signs and symptoms in glycogen storage disease type IX include:

- Enlarged liver

- Slowed growth

- Motor development delay (mild)

- Low blood sugar accompanied by ketosis

- Lack of muscle tone

Most of these signs and symptoms diminish as adulthood sets in.

Gangliosidosis contains different types of lipid storage disorders caused by the accumulation of lipids known as gangliosides. There are two distinct genetic causes of the disease. Both are autosomal recessive and affect males and females equally.

Symptoms of ML III are often not noticed until the child is 3–5 years of age. Patients with ML III are generally of normal intelligence (trait) or have only mild mental retardation. These patients usually have skeletal abnormalities, coarse facial features, short height, corneal clouding, carpal tunnel syndrome, aortic valve disease and mild enlargement of organs. Some children with severe forms of this disease do not live beyond childhood. However, there is a great variability among patients - there are diagnosed individuals with ML III living in their sixties.

Symptoms are related to the organs in which sphingomyelin accumulates. Enlargement of the liver and spleen (hepatosplenomegaly) may cause reduced appetite, abdominal distension, and pain. Enlargement of the spleen (splenomegaly) may also cause low levels of platelets in the blood (thrombocytopenia).

Accumulation of sphingomyelin in the central nervous system (including the cerebellum) results in unsteady gait (ataxia), slurring of speech (dysarthria), and difficulty in swallowing (dysphagia). Basal ganglia dysfunction causes abnormal posturing of the limbs, trunk, and face (dystonia). Upper brainstem disease results in impaired voluntary rapid eye movements (supranuclear gaze palsy). More widespread disease involving the cerebral cortex and subcortical structures causes gradual loss of intellectual abilities, causing dementia and seizures.

Bones also may be affected: symptoms may include enlarged bone marrow cavities, thinned cortical bone, or a distortion of the hip bone called coxa vara. Sleep-related disorders, such as sleep inversion, sleepiness during the day and wakefulness at night, may occur. Gelastic cataplexy, the sudden loss of muscle tone when the affected patient laughs, is also seen.

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

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

Individuals with Salla disease may present with nystagmus in the first months of life as well as hypotonia, reduced muscle tone and strength, and cognitive impairment. The most severely impaired children do not walk or acquire language, but the typical patient learns to walk and speak and has normal life expectancy. The MRI shows arrested or delayed myelination.

Glycogen storage disease type V (GSD-V) is a metabolic disorder, more specifically a glycogen storage disease, caused by a deficiency of myophosphorylase. Its incidence is reported as 1 in 100,000, approximately the same as glycogen storage disease type I.

The disease was first reported in 1951 by Dr. Brian McArdle of Guy's Hospital, London.

Symptoms range widely in their onset and severity. The onset of the most severe form, type III, begins within the first months of life and includes a quick progression of intellectual disability, liver and spleen enlargement (splenomegaly), hearing loss, respiratory infections and skeletal abnormalities. Often the appearance of an affected individual includes the following facial features: protruding forehead, leveled nasal bridge, small nose and wide mouth. Muscular weakness or spinal abnormalities can occur due to the buildup of storage materials in the muscle. A milder form of alpha-mannosidosis involves mild to moderate intellectual disability which develops during childhood or adolescence.

Human PFK deficiency is categorized into four types: classic, late-onset, infantile and hemolytic. These types are differentiated by age at which symptoms are observed and which symptoms present.

Classic phosphofructokinase deficiency is the most common type of this disorder. This type presents with exercise-induced muscle cramps and weakness (sometimes rhabdomyolysis), myoglobinuria, as well as with haemolytic anaemia causing dark urine a few hours later.

Hyperuricemia is common, due to the kidneys' inability to process uric acid following damage resulting from processing myoglobin. Nausea and vomiting following strenuous exercise is another common indicator of classic PFK deficiency. Many patients will also display high levels of bilirubin, which can lead to a jaundiced appearance. Symptoms for this type of PFK deficiency usually appear in early childhood.

A prenatal diagnosis was made by Kleijer et al. in 1979 by measuring beta-galactosidase and neuraminidase activities in cultured amniotic fluid cells.

Patients generally have a benign course, and typically present with hepatomegaly and growth retardation early in childhood. Mild hypoglycemia, hyperlipidemia, and hyperketosis may occur. Lactic acid and uric acid levels may be normal. However, lactic acidosis may occur during fasting.

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.

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

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.