ARSACS is usually diagnosed in early childhood, approximately 12–24 months of age when a child begins to take their first steps. At this time it manifests as a lack of coordination and balance resulting in frequent falls. Some of the signs and symptoms include:

- Stiffness of the legs

- Appendicular and trunk ataxia

- Hollow foot and hand deformities

- Ataxic dysarthria

- Distal muscle wasting

- Horizontal gaze nystagmus

- Spasticity

Symptoms depend on the type of HSP inherited. The main feature of the disease is progressive spasticity in the lower limbs due to pyramidal tract dysfunction. This also results in brisk reflexes, extensor plantar reflexes, muscle weakness, and variable bladder disturbances. Furthermore, among the core symptoms of HSP are also included abnormal gait and difficulty in walking, decreased vibratory sense at the ankles, and paresthesia.

Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. Symptoms of HSP may begin at any age, from infancy to older than 60 years. If symptoms begin during the teenage years or later, then spastic gait disturbance usually progresses over many years. Canes, walkers, and wheelchairs may eventually be required, although some people never require assistance devices.

More specifically, patients with the autosomal dominant pure form of HSP reveal normal facial and extraocular movement. Although jaw jerk may be brisk in older subjects, there is no speech disturbance or difficulty of swallowing. Upper extremity muscle tone and strength are normal. In the lower extremities, muscle tone is increased at the hamstrings, quadriceps and ankles. Weakness is most notable at the iliopsoas, tibialis anterior, and to a lesser extent, hamstring muscles.

In the complex form of the disorder, additional symptoms are present. These include: peripheral neuropathy, amyotrophy, ataxia, mental retardation, ichthyosis, epilepsy, optic neuropathy, dementia, deafness, or problems with speech, swallowing or breathing.

Anita Harding classified the HSP in a pure and complicated form. Pure HSP presents with spasticity in the lower limbs, associated with neurogenic bladder disturbance as well as lack of vibration sensitivity (pallhypesthesia). On the other hand, HSP is classified as complex when lower limb spasticity is combined with any additional neurological symptom.

This classification is subjective and patients with complex HSPs are sometimes diagnosed as having cerebellar ataxia with spasticity, mental retardation (with spasticity), or leukodystrophy. Some of the genes listed below have been described in other diseases than HSP before. Therefore, some key genes overlap with other disease groups.

In the past, HSP has been classified as early onset beginning in early childhood or later onset in adulthood. The age of onsets has two points of maximum at age 2 and around age 40. New findings propose that an earlier onset leads to a longer disease duration without loss of ambulation or the need for the use of a wheelchair. This was also described earlier, that later onset forms evolve more rapidly.

Most patients begin to use a wheelchair for movement around age 30-40. Death usually occurs in their 60s, but some have been reported to live longer.

Onset usually occurs within the first two decades of life, commonly in the teenage years or the twenties. Life expectancy is normal. High arch of the foot (pes cavus) is common. Patients also have trouble controlling their hands, due to muscle loss on the thumb side of the index finger and palm below the thumb. It is rare for a person with this disorder to lose the ability to walk, though changes in gait may occur later in life.

Frequency of this disorder is unknown.

In an individual with dHMN V, electromyography will show pure motor neuropathy, patterns of weakness without upper motor neuron damage, in the hands. Tendon reflexes will also appear normal. Clinical, electrophysiological, and pathological testing will show a lack of damage to sensory neurons, differentiating this disease from CMT.

At the beginning, affected individuals often notice the loss of pain and temperature sensation or all sensory modalities in their feet. As the disease progresses, the sensory abnormalities may extend up to the knees. However, they often do not notice sensory loss for a long time. Many affected individuals only become aware of the disease when they notice painless injuries and burns or when they seek medical advice for slowly healing wounds or foot ulcers. Foot ulcerations may appear due to permanent pressure, such as long walks or badly fitting shoes. Minor wounds or blisters may then lead to deep foot ulcerations. Once infection occurs, complications such as inflammation and destruction of the underlying bones may follow. Affected individuals who do not lose sensation may experience spontaneous pain. In addition, many affected individuals exhibit, to a variable degree, symmetrical distal muscle weakness and wasting.

HSAN I is characterized by marked sensory disturbances mainly as the loss of pain and temperature sensation in the distal parts of the lower limbs. The loss of sensation can also extend to the proximal parts of the lower limbs and the upper limbs as the disease progresses. Some affected individuals do not lose sensation, but instead experience severe shooting, burning, and lancinating pains in the limbs or in the trunk. Autonomic disturbances, if present, manifest as decreased sweating. The degree of motor disturbances is highly variable, even within families, ranging from absent to severe distal muscle weakness and wasting.

The disease progresses slowly, but often disables the affected individuals severely after a long duration. The onset of the disease varies between the 2nd and 5th decade of life, albeit congenital or childhood onset has occasionally been reported. With the progression of the disease, the affected individuals lose the ability to feel pain in their feet and legs. Minor injuries in the painless area can result in slow-healing wounds which, if not immediately recognized, can develop into chronic ulcerations. Once infection occurs, these ulcerations can result in severe complications that lead to foot deformity, such as inflammation of the underlying bones, spontaneous bone fractures, and progressive degeneration of weight-bearing joints. Furthermore, foot deformity promotes skin changes such as hyperkeratosis at pressure points. These complications may necessitate amputation of the affected foot.

Biopsies of severely affected sural nerve (short saphenous nerve) in patients with HSAN I showed evidence of neuronal degeneration. Only a very few myelinated fibers were observed some of which showed a sign of primary (segmental) demyelination. A reasonable number of unmyelinated axons remained, although the presence of stacks of flattened Schwann cell processes suggested unmyelinated axon loss. Electrophysiological testing provides additional evidence that neuronal degeneration underlies the disease. Sensory potentials are usually absent in the lower limbs but are often recordable or even normal in the upper limbs of the patients. In addition, motor conduction is slow, possibly implying a demyelinating process.

The characteristic symptom of Costeff syndrome is the onset of progressively worsening eyesight caused by degeneration of the optic nerve (optic atrophy) within the first few years of childhood, with the majority of affected individuals also developing motor disabilities later in childhood. Occasionally, people with Costeff syndrome may also experience mild cognitive disability.

It is type of 3-methylglutaconic aciduria, the hallmark of which is an increased level in the urinary concentrations of 3-methylglutaconic acid and 3-methylglutaric acid; this can allow diagnosis as early as at one year of age.

Those with Costeff syndrome typically experience the first symptoms of visual deterioration within the first few years of childhood, which manifests as the onset of progressively decreasing visual acuity. This decrease tends to continue with age, even after childhood.

The majority of people with Costeff syndrome develop movement problems and motor disabilities later in childhood, the two most significant of which are choreoathetosis and spasticity. The former causes involuntary erratic, jerky, and twisting movements (see chorea and athetosis), whereas the latter causes twitches and spastic tendencies.

These two symptoms are often severe enough to seriously disable an individual; among 36 people with Costeff syndrome, 17 experienced major motor disability as a result of choreoathetosis, and 12 experienced spasticity-related symptoms severe enough to do the same.

Ataxia (loss of muscle coordination) and speech impairment caused by dysarthria also occur in roughly 50% of cases, but are rarely seriously disabling.

Some individuals with Costeff disease also display mild cognitive impairment, though such cases are relatively infrequent.

Autosomal recessive cerebellar ataxia type 1 (ARCA1) is a condition characterized by progressive problems with movement. Signs and symptoms of the disorder first appear in early to mid-adulthood. People with this condition initially experience impaired speech (dysarthria), problems with coordination and balance (ataxia), or both. They may also have difficulty with movements that involve judging distance or scale (dysmetria). Other features of ARCA1 include abnormal eye movements (nystagmus) and problems following the movements of objects with their eyes. The movement problems are slowly progressive, often resulting in the need for a cane, walker, or wheelchair.

Hereditary sensory and autonomic neuropathy type I (HSAN I) or hereditary sensory neuropathy type I (HSN I) is a group of autosomal dominant inherited neurological diseases that affect the peripheral nervous system particularly on the sensory and autonomic functions. The hallmark of the disease is the marked loss of pain and temperature sensation in the distal parts of the lower limbs. The autonomic disturbances, if present, manifest as sweating abnormalities.

The beginning of the disease varies between adolescence and adulthood. Since affected individuals cannot feel pain, minor wounds or blisters in the painless area may not be immediately recognized and can develop into extensive and deep foot ulcerations. Once infection occurs, the complications such as inflammation and progressive destruction of the underlying bones may follow and may require amputation of the surrounding area.

HSAN I is the most common type among the five types of HSAN. As a heterogeneous group of diseases, HSAN I can be divided into five subtypes HSAN IA-E. Most of the genes associated with the diseases have been identified. However, the molecular pathways leading to the manifestation of the diseases are not fully understood. Therefore, the potential targets for therapeutic interventions are not known. Moreover, gene-based therapies for patients with the diseases are not available to date, hence supportive care is the only treatment available for the patients.

The diagnosis of PMD is often first suggested after identification by magnetic resonance imaging (MRI) of abnormal white matter (high T2 signal intensity, i.e. T2 lengthening) throughout the brain, which is typically evident by about 1 year of age, but more subtle abnormalities should be evident during infancy. Unless there is a family history consistent with sex-linked inheritance, the condition is often misdiagnosed as cerebral palsy. Once a "PLP1" or "GJA12" mutation is identified, prenatal diagnosis or preimplantation genetic diagnostic testing is possible.

Pelizaeus–Merzbacher disease (PMD) is a rare central nervous system disorder in which coordination, motor abilities, and intellectual function are delayed to variable extents.

Most cases of autosomal recessive cerebellar ataxia are early onset, usually around the age of 20. People with this type of ataxia share many characteristic symptoms including:

- frequent falls due to poor balance

- imprecise hand coordination

- postural or kinetic tremor of extremities or trunk

- dysarthria

- dysphasia

- vertigo

- diplopia

- lower extremity tendon reflexes

- dysmetria

- minor abnormalities in ocular saccades

- attention defects

- impaired verbal working memory and visuospatial skills

- Normal life expectancy

Autosomal recessive ataxias are generally associated with a loss of proprioception and vibration sense. Arreflexia is more common in autosomal recessive ataxia than autosomal dominant ataxias. Also, they tend to have more involvement outside of the nervous system. Mutations in subunit of the mitochondrial DNA polymerase (POLG) have been found to be a potential cause of autosomal recessive cerebellar ataxia.

Costeff syndrome, or 3-methylglutaconic aciduria type III, is a genetic disorder caused by mutations in the "OPA3" gene. It is typically associated with the onset of visual deterioration (optic atrophy) in early childhood followed by the development of movement problems and motor disability in later childhood, occasionally along with mild cases of cognitive deficiency. The disorder is named after Hanan Costeff, the doctor who first described the syndrome in 1989.

Spastic ataxia-corneal dystrophy syndrome (also known as Bedouin spastic ataxia syndrome) is an autosomally resessive disease. It has been found in an inbred Bedouin family. It was first described in 1986. A member of the family who was first diagnosed with this disease also had Bartter syndrome. It was concluded by its first descriptors Mousa-Al et al. that the disease is different from a disease known as corneal-cerebellar syndrome that had been found in 1985.

Symptoms include spastic ataxia, cataracts, macular corneal dystrophy and nonaxial myopia. Mental development is normal.

Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills.

In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly.

Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. Generally they have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding and breathing problems that can lead to frequent infections, such as pneumonia. Seizures occur in some affected children.

Rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and vision loss due to deterioration (atrophy) of the optic nerve are characteristic of infantile neuroaxonal dystrophy. Hearing loss may also develop. Children with this disorder experience progressive deterioration of cognitive functions (dementia), and eventually lose awareness of their surroundings.

Infantile neuroaxonal dystrophy is characterized by the development of swellings called spheroid bodies in the axons, the fibers that extend from nerve cells (neurons) and transmit impulses to muscles and other neurons. A part of the brain called the cerebellum, which helps to control movements, may also be damaged. In some individuals with infantile neuroaxonal dystrophy, abnormal amounts of iron accumulate in a specific region of the brain called the basal ganglia.

Acheiropodia (ACHP), also known as Horn-Kolb Syndrome, Acheiropody and Aleijadinhos (Brazilian type), is an autosomal recessive disorder that results in hemimelia, a lack of formation of the distal extremities.

This is a congenital defect which consists of bilateral amputations of the distal upper and lower extremities, as well as aplasia of the hands and feet. It was first discovered and is prevalent almost exclusively in Brazil.

The acronym "MASA" describes the four major symptoms - Mental retardation, Aphasia, Shuffling gait, and Adducted thumbs. Another name for this syndrome is "L1 syndrome".

The term "CRASH", for "corpus callosum hypoplasia, retardation, adducted thumbs, spastic paraplegia, and hydrocephalus" has also been used to describe L1CAM-related disorders.

The combination of muscular hypotonia and fixed dilated pupils in infancy is suspicious of Gillespie syndrome. Early onset partial aniridia, cerebellar ataxia, and mental retardation are hallmark of syndrome. The iris abnormality is specific and seems pathognomonic of Gillespie syndrome. The aniridia consisting of a superior coloboma and inferior iris hypoplasia, foveomacular dysplasia.

Atypical Gillespie syndrome associated with bilateral ptosis, exotropia, correctopia, iris hypoplasia, anterior capsular lens opacities, foveal hypoplasia, retinal vascular tortuosity, and retinal hypopigmentation.

Neurological signs ar nystagmus, mild craniofacial asymmetry, axial hypotonia, developmental delay, and mild mental retardation. Mariën P did not support the prevailing view of a global mental retardation as a cardinal feature of Gillespie syndrome but primarily reflect cerebellar induced neurobehavioral dysfunctions following disruption of the cerebrocerebellar anatomical circuitry that closely resembles the "cerebellar cognitive and affective syndrome" (CeCAS).

Congenital pulmonary stenosis and helix dysplasia can be associated.

Some of the signs of Tropical spastic paraparesis are:

- Leg instability

- Urinary dysfunction.

- Bowel dysfunction

- Back pain

- Erectile problems

- Psoriasis

Patients with TSP may also exhibit uveitis (inflammation of the uveal tract of the eye), arthritis (inflammation of one or more joints), pulmonary lymphocytic alveolitis (inflammation of the lung tissues), polymyositis (an inflammatory muscle disease), keratoconjunctivitis sicca (persistent dryness of the cornea and conjunctiva), and infectious dermatitis (inflammation of the skin).

HTLV-1 can be transmitted via breastfeeding (mother to child), sexual contact, via blood contact (transfusion or needle sharing).

CCD causes persistent secretory diarrhea. In a fetus, it leads to polyhydramnios and premature birth. Immediately after birth, it leads to dehydration, hypoelectrolytemia, hyperbilirubinemia, abdominal distention, and failure to thrive.

Sarcosinemia (SAR), also called hypersarcosinemia and SARDH deficiency, is a rare autosomal recessive metabolic disorder characterized by an increased concentration of sarcosine in blood plasma and urine ("sarcosinuria"). It can result from an inborn error of sarcosine metabolism, or from severe folate deficiency related to the folate requirement for the conversion of sarcosine to glycine. It is thought to be a relatively benign condition.

Fitzsimmons–Guilbert syndrome is an extremely rare genetic disease characterized by a slowly progressive spastic paraplegia, skeletal anomalies of the hands and feet with brachydactyly type E, cone-shaped epiphyses, abnormal metaphyseal–phalangeal pattern profile, sternal anomaly (pectus carinatum or excavatum), dysarthria, and mild intellectual deficit.

With so few described cases, establishing the basic pathophysiological mechanisms or genetic abnormalities has not been possible.