This exclusively myopathic form is the most prevalent and least severe phenotypic presentation of this disorder. Characteristic signs and symptoms include rhabdomyolysis (breakdown of muscle fibers and subsequent release of myoglobin), myoglobinuria, recurrent muscle pain, and weakness. It is important to note that muscle weakness and pain typically resolves within hours to days, and patients appear clinically normal in the intervening periods between attacks. Symptoms are most often exercise-induced, but fasting, a high-fat diet, exposure to cold temperature, or infection (especially febrile illness) can also provoke this metabolic myopathy. In a minority of cases, disease severity can be exacerbated by three life-threatening complications resulting from persistent rhabdomyolysis: acute kidney failure, respiratory insufficiency, and episodic abnormal heart rhythms. Severe forms may have continual pain from general life activity. The adult form has a variable age of onset. The first appearance of symptoms usually occurs between 6 and 20 years of age but has been documented in patients as young as 8 months as well as in adults over the age of 50. Roughly 80% cases reported to date have been male.

There are three main types of carnitine palmitoyltransferase II deficiency classified on the basis of tissue-specific symptomotology and age of onset:

- Mild to severe adult myopathic form

- Severe infantile multisystemic form

- Lethal neonatal form

It should be noted that among the few people diagnosed with CPT2, some have unknown and/or novel mutations that place them outside these three categories while remaining positive for CPT2.

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.

Phosphofructokinase deficiency also presents in a rare infantile form. Infants with this deficiency often display floppy infant syndrome (hypotonia), arthrogryposis, encephalopathy and cardiomyopathy. The disorder can also manifest itself in the central nervous system, usually in the form of seizures. PFK deficient infants also often have some type of respiratory issue. Survival rate for the infantile form of PFK deficiency is low, and the cause of death is often due to respiratory failure.

The defining characteristic of this form of the disorder is hemolytic anemia, in which red blood cells break down prematurely. Muscle weakness and pain are not as common in patients with hemolytic PFK deficiency.

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.

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.

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.

Clinically, patients affected with HCP present similarly to those with other acute porphyrias, such as acute intermittent porphyria (AIP) and variegate porphyria (VP). Patients with HCP and VP can present with symptoms shared between the acute and cutaneous porphyrias. This includes the acute attacks of abdominal pain, nausea, vomiting, diarrhea, tachycardia, hypertension and seizures, as well as the cutaneous findings seen in porphyria cutanea tarda (PCT), namely increased skin fragility, bullous lesions after exposure to sunlight and increased scarring.

Individuals with HCP may be asymptomatic in the absence of triggering factors. Common triggers include certain drugs, alcohol, hormonal changes, and dietary changes. Sunlight and other ultraviolet light can trigger the skin manifestations. Homozygous individuals for "CPOX" mutations can present with these findings at an earlier age than heterozygotes.

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

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

D-Bifunctional protein deficiency (officially called 17β-hydroxysteroid dehydrogenase IV deficiency) is an autosomal recessive peroxisomal fatty acid oxidation disorder. Peroxisomal disorders are usually caused by a combination of peroxisomal assembly defects or by deficiencies of specific peroxisomal enzymes. The peroxisome is an organelle in the cell similar to the lysosome that functions to detoxify the cell. Peroxisomes contain many different enzymes, such as catalase, and their main function is to neutralize free radicals and detoxify drugs, such as alcohol. For this reason peroxisomes are ubiquitous in the liver and kidney. D-BP deficiency is the most severe peroxisomal disorder, often resembling Zellweger syndrome.

Characteristics of the disorder include neonatal hypotonia and seizures, occurring mostly within the first month of life, as well as visual and hearing impairment. Other symptoms include severe craniofacial disfiguration, psychomotor delay, and neuronal migration defects. Most onsets of the disorder begin in the gestational weeks of development and most affected individuals die within the first two years of life.

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).

Like many other genetic disorders that affect lipid metabolism, there are several forms of MLD, which are late infantile, juvenile, and adult.

- In the "late infantile form", which is the most common form of MLD (50–60%), affected children begin having difficulty walking after the first year of life, usually at 15–24 months. Symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. Children may become comatose. Untreated, most children with this form of MLD die by age 5, often much sooner.

- Children with the "juvenile form" of MLD (onset between 3 and 10 years of age) usually begin with impaired school performance, mental deterioration, and dementia and then develop symptoms similar to the late infantile form but with slower progression. Age of death is variable, but normally within 10 to 15 years of symptom onset although some juveniles can live for several decades or longer after onset.

- The "adult form" commonly begins after age 16 often with an onset in the 4th or 5th decade of life and presents as a psychiatric disorder or progressive dementia. Adult-onset MLD usually progresses more slowly than the late infantile and juvenile forms, with a protracted course of a decade or more.

Palliative care can help with many of the symptoms and usually improves quality of life and longevity.

Carriers have low enzyme levels compared to their family population ("normal" levels vary from family to family) but even low enzyme levels are adequate to process the body's sulfatide.

Glycerol Kinase Deficiency causes the condition known as hyperglycerolemia, an accumulation of glycerol in the blood and urine. This excess of glycerol in bodily fluids can lead to many more potentially dangerous symptoms. Common symptoms include vomiting and lethargy. These tend to be the only symptoms, if any, present in adult GKD which has been found to present with fewer symptoms than infant or juvenile GKD. When GKD is accompanied by Duchenne Muscular Dystrophy and Adrenal Hypoplasia Congenita, also caused by mutations on the Xp21 chromosome, the symptoms can become much more severe. Symptoms visible at or shortly after birth include:

- cryptorchidism

- strabismus

- seizures

Some other symptoms that become more noticeable with time would be:

- metabolic acidosis

- hypoglycemia

- adrenal cortex insufficiency

- learning disabilities

- osteoporosis

- myopathy

Many of the physically visible symptoms, such as cryptorchidism, strabismus, learning disabilities, and myopathy, tend to have an added psychological effect on the subject due to the fact that they can set him or her apart from those without GKD. Cryptorchidism, the failure of one or both of the testes to descend to the scrotum, has been known to lead to sexual identity confusion amongst young boys because it is such a major physiological anomaly. Strabismus is the misalignment of one’s eyes. Typically, one is focused but the other is “lazy” and is directed inward or out ward (up and down is less common but does occur).

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.

It is difficult to determine the prevalence of hyperprolinemia type I, as many people with the condition are asymptomatic.

People with hyperprolinemia type I have proline levels in their blood between 3 and 10 times the normal level. Some individuals with type I exhibit seizures, intellectual disability, or other neurological problems.

Glycerol Kinase Deficiency (GKD) is an X-linked recessive enzyme defect that is heterozygous in nature. Three clinically distinct forms of this deficiency have been proposed, namely infantile, juvenile, and adult. National Institutes of Health and its Office of Rare Diseases Research (ORDR) branch classifies GKD as a rare disease, known to affect fewer than 200,000 individuals in the United States. The responsible gene lies in a region containing genes in which deletions can cause Duchenne muscular dystrophy and adrenal hypoplasia congenita. Combinations of these three genetic defects including GKD are addressed medically as Complex GKD.

Hereditary coproporphyria (HCP) is a disorder of heme biosynthesis, classified as an acute hepatic porphyria. HCP is caused by a deficiency of the enzyme coproporphyrinogen oxidase, coded for by the "CPOX" gene, and is inherited in an autosomal dominant fashion, although homozygous individuals have been identified. Unlike acute intermittent porphyria, individuals with HCP can present with cutaneous findings similar to those found in porphyria cutanea tarda in addition to the acute attacks of abdominal pain, vomiting and neurological dysfunction characteristic of acute porphyrias. Like other porphyrias, attacks of HCP can be induced by certain drugs, environmental stressors or diet changes. Biochemical and molecular testing can be used to narrow down the diagnosis of a porphyria and identify the specific genetic defect. Overall, porphyrias are rare diseases. The combined incidence for all forms of the disease has been estimated at 1:20,000. The exact incidence of HCP is difficult to determine, due to its reduced penetrance.

Hyperprolinemia, also referred to as prolinemia or prolinuria, is a condition which occurs when the amino acid proline is not broken down properly by the enzymes proline oxidase or pyrroline-5-carboxylate dehydrogenase, causing a buildup of proline in the body.

Tay–Sachs disease is a rare autosomal recessive genetic disorder that causes a progressive deterioration of nerve cells and of mental and physical abilities that begins around six months of age and usually results in death by the age of four. It is the most common of the GM2 gangliosidoses. The disease occurs when harmful quantities of cell membrane gangliosides accumulate in the brain's nerve cells, eventually leading to the premature death of the cells.

Males show more serious symptoms than females affected by this disorder.

The symptoms for males are:

1. Profound sensorineural hearing loss i.e, a complete or almost complete loss of hearing caused by abnormalities in the inner ear.

2. Weak muscle tone - Hypotonia.

3. Impaired muscle coordination - Ataxia.

4. Developmental delay.

5. Intellecual disability.

6. Vision loss caused by optic nerve atrophy in early childhood.

7. Peripheral neuropathy.

8. Recurrent infections, especially in the respiratory system.

9. Muscle weakness caused by recurrent infections.

Symptoms for females:

Very rarely seen hearing loss that begins in adulthood (age > 20 years) combined with ataxia and neuropathy. Optic atrophy and retinitis pigmentosa observed in some cases too.

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.

Signs and symptoms of GM2-gangliosidosis, AB variant are identical with those of infantile Tay-Sachs disease, except that enzyme assay testing shows normal levels of hexosaminidase A. Infantile Sandhoff disease has similar symptoms and prognosis, except that there is deficiency of both hexosaminidase A and hexosaminidase B. 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, mental retardation, and paralysis.

An ophthalmological abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. This cherry-red spot is the same finding that Warren Tay first reported in 1881, when he identified a case of Tay-Sachs disease, and it has the same etiology.

The prognosis for AB variant is the same as for infantile Tay-Sachs disease. Children with AB variant die in infancy or early childhood.

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.