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.

Some specific symptoms vary from one type of leukodystrophy to the next but the vast majority of symptoms are shared as the causes for the disease generally have the same effects. Symptoms are dependent on the age of onset, which is predominantly in infancy and early childhood, although the exact time of onset may be difficult to determine. Hyperirritability and hypersensitivity to the environment are common, as well as some tell-tale physical signs including muscle rigidity and a backwards-bent head. Botox therapy is often used to treat patients with spasticity. Juvenile and adult onsets display similar symptoms including a decrease or loss in hearing and vision. While children do experience optic and auditory degeneration, the course of the disease is usually too rapid, causing death relatively quickly, whereas adults may live with these conditions for many years. In children, spastic activity often precedes progressive ataxia and rapid cognitive deterioration which has been described as mental retardation. Epilepsy is commonplace for patients of all ages. More progressed patients show weakness in deglutition, leading to spastic coughing fits due to inhaled saliva. Classic symptomatic progression of juvenile x-linked adrenoleukodystrophy is shown in the 1992 film, "Lorenzo's Oil".

Course and timetable are dependent on the age of onset with infants showing a lifespan of 2–8 years, juveniles 2–10 years and adults typically 10+ years. Adults typically see an extended period of stability followed by a decline to a vegetative state and death. While treatments do exist, most are in the experimental phase and can only promise a halt in the progression of symptoms, although some gene therapies have shown some symptomatic improvement. The debilitating course of the disease has led to numerous philosophical and ethical arguments over experimental clinical trials, patients’ rights and physician-assisted suicide.

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.

Leukodystrophy is one of a group of disorders characterized by degeneration of the white matter in the brain. The word "leukodystrophy" comes from the Greek roots "leuko", "white", "dys", "abnormal", and "troph", "growth". The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers.

When damage occurs to white matter, immune responses can lead to inflammation in the CNS, along with loss of myelin. The degeneration of white matter can be seen in a MRI and used to diagnose leukodystrophy. Leukodystrophy is characterized by specific symptoms including decreased motor function, muscle rigidity, and eventually degeneration of sight and hearing. While the disease is fatal, the age of onset is a key factor as infants are given a lifespan of 2–8 years (sometimes longer), while adults typically live more than a decade after onset. There is a great lack of treatment, although cord blood and hematopoietic stem cell transplantation (bone marrow transplant) seem to help in certain types while further research is being done.

The combined incidence of the leukodystrophies is estimated at 1:7,600. The majority of types involve the inheritance of a recessive, dominant, or X-linked trait, while others, although involving a defective gene, are the result of spontaneous mutation rather than genetic inheritance.

The disease is one in a group of genetic disorders collectively known as leukodystrophies that affect growth of the myelin sheath, the fatty covering—which acts as an insulator—on nerve fibers in the CNS. PMD is generally caused by a recessive mutation of the gene on the long arm of the X-chromosome (Xq21-22) that codes for a myelin protein called proteolipid protein 1 or PLP1.

The onset of Pelizaeus–Merzbacher disease is usually in early infancy. The most characteristic early signs are nystagmus (rapid, involuntary, rhythmic motion of the eyes) and hypotonia (low muscle tone). Motor abilities are delayed or never acquired, mostly depending upon the severity of the mutation. Most children with PMD learn to understand language, and usually have some speech. Other signs may include tremor, lack of coordination, involuntary movements, weakness, unsteady gait, and over time, spasticity in legs and arms. Muscle contractures (shrinkage or shortening of a muscle) often occur over time. Mental functions may deteriorate. Some patients may have convulsions and skeletal deformation, such as scoliosis, resulting from abnormal muscular stress on bones.

There are several forms of Pelizaeus–Merzbacher disease including classic, connatal, transitional, and adult variants. The majority of disease-causing mutations result in duplications of the entire PLP1 gene. Interestingly, deletions at the PLP1 locus (which are rarer) cause a milder form of PMD than is observed with the typical duplication mutations, which demonstrates the critical importance of gene dosage at this locus for normal CNS function. Some of the remaining cases of PMD are accounted for by mutations in the gap junction A12 ("GJA12") gene, and are now called Pelizaeus-Merzbacher-like disease (PMLD). Other cases of apparent PMD do not have mutations in either the "PLP1" or "GJA12" genes, and are presumed to be caused either by mutations in other genes, or by mutations not detected by sequencing the "PLP1" gene exons and neighboring intronic regions of the gene. Among these is a new genetic disorder (discovered in 2003, 2004) which is caused by mutation in the transporter of thyroid hormone, MCT8, also known as SLC16A2, is believed to be account for a significant fraction of the undiagnosed neurological disorders (usually resulting in hypotonic/floppy infants with delayed milestones). This genetic defect was known as Allan–Herndon–Dudley syndrome (since 1944) without knowing its actual cause. Some of the signs for this disorder are as follows: normal to slightly elevated TSH, elevated T and reduced T (ratio of T/T is about double its normal value). Normal looking at birth and for the first few years, hypotonic (floppy), in particular difficulty to hold the head, possibly difficulty to thrive, possibly with delayed myelination (if so, some cases are reported with an MRI pattern similar to Pelizaeus–Merzbacher disease, known as PMD,) possibly with decreased mitochondrial enzyme activities, possibly with fluctuating lactate level. Patients have an alert face, a limited IQ, patients may never talk/walk, 50% need feeding tube, patients have a normal life span. MCT8 can be ruled out with a simple TSH/T/T thyroid test.

Milder mutations of the "PLP1" gene that mainly cause leg weakness and spasticity, with little or no cerebral involvement, are classified as spastic paraplegia 2 (SPG2).

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.

Delays in development of some physical, psychological and behavioral skills; progressive enlargement of the head (macrocephaly), seizures, spasticity, and in some cases also hydrocephalus, idiopathic intracranial hypertension, and dementia.

The prognosis is generally poor. With early onset, death usually occurs within 10 years from the onset of symptoms. Individuals with the infantile form usually die before the age of 7. Usually, the later the disease occurs, the slower its course is.

Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder that affects many parts of the body. It is characterized by delayed development and delayed mental progression, distinctive facial features, unusually flexible joints, and loose folds of extra skin, especially on the hands and feet. Heart abnormalities are common, including a very fast heartbeat (tachycardia), structural heart defects, and overgrowth of the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be large at birth, but grow more slowly than other children and have difficulty feeding. Later in life, people with this condition have relatively short stature and many have reduced levels of growth hormones. It is a RASopathy.

Beginning in early childhood, people with Costello syndrome have an increased risk of developing certain cancerous and noncancerous tumors. Small growths called papillomas are the most common noncancerous tumors seen with this condition. They usually develop around the nose and mouth or near the anus. The most frequent cancerous tumor associated with Costello syndrome is a soft tissue tumor called a rhabdomyosarcoma. Other cancers also have been reported in children and adolescents with this disorder, including a tumor that arises in developing nerve cells (neuroblastoma) and a form of bladder cancer (transitional cell carcinoma).

Costello Syndrome was discovered by Dr Jack Costello, a New Zealand Paediatrician in 1977. He is credited with first reporting the syndrome in the Australian Paediatric Journal, Volume 13, No.2 in 1977.

Clinically, PASLI disease is characterized by recurrent sinopulmonary infections that can lead to progressive airway damage. Patients also suffer from lymphoproliferation (large lymph nodes and spleen), chronic viremia due to EBV or CMV, distinctive lymphoid nodules at mucosal surfaces, autoimmune cytopenias, and EBV-driven B cell lymphoma. Importantly, the clinical presentations and disease courses are variable with some individuals severely affected, whereas others show little manifestation of disease. This “variable expressivity,” even within the same family, can be striking and may be explained by differences in lifestyle, exposure to pathogens, treatment efficacy, or other genetic modifiers.

PASLI disease is a rare genetic disorder of the immune system. PASLI stands for “p110 delta activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency.” The immunodeficiency manifests as recurrent infections usually starting in childhood. These include bacterial infections of the respiratory system and chronic viremia due to Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV). Individuals with PASLI disease also have an increased risk of EBV-associated lymphoma. Investigators Carrie Lucas, Michael Lenardo, and Gulbu Uzel at the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health and Sergey Nejentsev at the University of Cambridge, UK simultaneously described a mutation causing this condition which they called Activated PI3K Delta Syndrome (APDS).

Viliuisk Encephalomyelitis (VE) is a fatal progressive neurological disorder found only in the Sakha (Iakut/Yakut) population of central Siberia. About 15 new cases are reported each year. VE is a very rare disease and little research has been conducted. The causative agents, origin of the disease, and involved candidate genes are currently unknown, but much research has been done in pursuit of the answers.

Those inflicted with the disease survive for a period of only a few months to several years. VE follows three main courses of infection: an acute form, a sub-acute form subsiding into a progressive form, and a chronic form. Initially, the infected patients experience symptoms such as: severe headaches, delirium, lethargy, meningism, bradykinesia, and incoordination. A small percentage of patients die during the acute phase as result of a severe coma. In all cases the disease is fatal.

Babinski–Nageotte syndrome, sometimes called Babinski syndrome or hemimedullary syndrome, is an alternating brainstem syndrome. It occurs when there is damage to the dorsolateral or posterior lateral medulla oblongata, likely syphilitic in origin. Hence it is also called the alternating medulla oblongata syndrome.

The rare disorder is caused by damage to a part of the brain (medullobulbar transitional area) which causes a variety of neurological symptoms, some of which affect only one side of the body. Symptoms include ipsilateral (same side) cerebellar ataxia, sensory deficits of the face, and Horner's syndrome, along with weakness and loss of sensation on the contralateral (opposite side) of the body.

It was first described in 1902 and later named after the neurologists who initially investigated it, Joseph Babinski and Jean Nageotte.

Patients with Stargardt disease usually develop symptoms in the mid-first to the late second decade of life, with age of onset which can be as early as ~6 years of age. The main symptom of Stargardt disease is loss of visual acuity, uncorrectable with glasses, which progresses and frequently stabilizes between 20/200 and 20/400. Other symptoms include wavy vision, blind spots (scotomata), blurriness, impaired color vision, and difficulty adapting to dim lighting (delayed dark adaptation). The disease sometimes causes sensitivity to glare; overcast days offer some relief. Vision is most noticeably impaired when the macula (center of retina and focus of vision) is damaged, leaving peripheral vision more intact. Generally, vision loss starts within the first 20 years of life.

Examination with an ophthalmoscope shows few notable findings in the early stages of the disease. Eventually, however, an oval-shaped atrophy with a horizontal major axis appears in the retinal pigment epithelium, and has the appearance of beaten bronze, along with sparing of the area surrounding the optic disc (peripapillary sparing). Techniques such as fundus autofluorescence (FAF), Optical Coherence Tomography (OCT), or less frequently fluorescein angiography, can detect early signs before they are visible ophthalmoscopically.

As of 2007, fewer than 500 Yakut individuals have been infected with VE. Viliuisk Encephalomyelitis is classified as a progressive neurological disorder that ultimately ends in the death of the infected individual. The disease has three distinguishable phases: The acute form, the progressive form, and the chronic form.

The acute form is the most rapid and most violent of all the stages. It begins with the characteristic rigidity of the muscles, accompanied by slurred speech, severe headaches, and exaggeration of cold-like symptoms. Patients usually die within weeks of the initial symptoms. Routine post-mortem examinations yield: severe inflammation of the brain lining, clusters of dead cells and tissue, and largely increased amounts of macrophages and lymphocytes.

The progressive form is the most common case. Patients initially experience acute-like symptoms which are not as severe, and subside within a few weeks. Following the sub-acute phase, the patients experience a few mild symptoms including some behavioral changes, incoordination, and difficulty in speech. Eventually the disease developed fully and those infected were stricken with the characteristic symptoms of rigidity, slurred speech, and deterioration of cognitive functions. Ultimately, brain function depreciates rapidly resulting in death.

Many patients who undergo the chronic form claim never to have had an acute attack. These patients endure varying measures of impairment and suffer mental deterioration for the remainder of their lives. Usually they live to be very old and succumb to other diseases.

In almost all cases there are changes characteristic of VE. Early onset shows an increased number of lymphocytes and increased protein concentration — which reduces over many years. These factors help neurologists determine the form of VE based on progression. The trademark changes in the brain include: thickened inflamed meninges, necrotic cortical lesions, increased number of lymphocytes, and neuronal death.

BENTA disease is a rare genetic disorder of the immune system. BENTA stands for "B cell expansion with NF-κB and T cell anergy" and is caused by germline heterozygous gain-of-function mutations in the gene CARD11 (see OMIM entry #607210). This disorder is characterized by polyclonal B cell lymphocytosis with onset in infancy, splenomegaly, lymphadenopathy, mild immunodeficiency, and increased risk of lymphoma. Investigators Andrew L. Snow and Michael J. Lenardo at the National Institute of Allergy and Infectious Disease at the U.S. National Institutes of Health first characterized BENTA disease in 2012. Dr. Snow's current laboratory at the Uniformed Services University of the Health Sciences is now actively studying this disorder.

Endocardial fibroelastosis (EFE) is a rare heart disorder usually occurring in children two years old and younger. It may also be considered a reaction to stress, not necessarily a specific disease.

It should not be confused with endomyocardial fibrosis.

Stargardt disease, or fundus flavimaculatus, is the most frequent form of inherited juvenile macular degeneration. Stargardt causes progressive vision loss usually to the point of legal blindness. Several genes are associated with the disorder. Symptoms, mainly central vision loss, typically develop before age 20 (median age of onset: ~17 years old), and also include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting (dark adaptation delays).

Stargardt is often used to refer to any juvenile macular dystrophy; however, it properly refers to atrophic macular dystrophy with yellow, poorly-defined flecks surrounding the macula in the retinal pigment epithelium.

Individuals with BENTA disease have polyclonal B cell lymphocytosis (i.e. excess B cells) developing in infancy, in addition to splenomegaly and lymphadenopathy. Patients may have low serum IgM and mildly anergic T cells. These features likely contribute to the mild immunodeficiency seen with BENTA disease. Patients are generally susceptible to recurrent sinopulmonary and ear infections in childhood, and may be more susceptible to certain viruses including Epstein-Barr virus, BK virus, and molluscum contagiosum.

The disease primarily affects people age 30 to 60 years of age. People moving to endemic areas do not develop the condition until living there for 15 years.

It can cause the kidneys to fail (end-stage renal disease, or ESRD) forcing a patient to start dialysis or receive a kidney transplant. In endemic areas BEN is responsible for up to 70% of ESRD. At least 25,000 individuals are known to have the disease.

Symptoms include weakness, anemia, and a coppery skin discoloration

A later finding, usually after kidney failure occurs, is transitional cancer of urothelial tract. While most urothelial cancer is in the bladder, BEN has an increased rate of the upper tract (renal pelvis and ureters).

Spanish researchers reported the development of a Costello mouse, with the G12V mutation, in early 2008. Although the G12V mutation is rare among children with Costello syndrome, and the G12V mouse does not appear to develop tumors as expected, information about the mouse model's heart may be transferrable to humans.

Italian and Japanese researchers published their development of a Costello zebrafish in late 2008, also with the G12V mutation. The advent of animal models may accelerate identification of treatment options.

The characteristic symptom of Degos disease is the development of papules. Initially, individuals may have skin lesions or rashes, but they will proceed to develop distinct bumps, or papules. Papules are circular in shape, have a porcelain-white center and red border. As papules age, the white centers will skin in and only the border will remain raised. Typically, papules range from 0.5 to 1 cm in width. Papules appear on the trunk and upper extremities and are not found on the individual's palms, soles, scalp, or face.

Depending on whether an individual has the benign variant or malignant variant of the disease symptoms will vary. Both the benign and malignant forms have development of the characteristic papules. Individuals with the benign form will have the typical papules persisting anywhere from a few years to throughout their whole lives. In the benign form, no inner organs are affected. If an individual develops the malignant form, it means that not only are the papules present, but inner organs are involved. Most malignant cases involve problems of the gastrointestinal tract leading to small intestine lesions, abdominal pain, diarrhea, and bowel perforation. If the central nervous system is involved, symptoms can include headaches, dizziness, seizures, paralysis of cranial nerves, weakness, stroke, damage to small areas of the brain due to artery blockage (cerebral infarcts, and cerebral hemorrhage). Additional organs commonly impacted include the heart, lungs, and kidneys. Symptoms that may develop from damage to these organs include double vision (diploplia), clouding of lenses of eyes, swelling of the optic disc (papilledema), partial loss of vision, shortness of breath, chest pain, epilepsy,and thickening of pericardium.

Someone with the benign form may suddenly develop symptoms of the malignant form. Symptoms can last anywhere from a few weeks to several years. Onset of symptoms typically begins to manifest between the ages of 20-50. A few cases of this condition in newborns have also been described.

EFE is characterized by a thickening of the innermost lining of the heart chambers (the endocardium) due to an increase in the amount of supporting connective tissue and elastic fibres. It is an uncommon cause of unexplained heart failure in infants and children, and is one component of HEC syndrome. Fibroelastosis is strongly seen as a primary cause of restrictive cardiomyopathy in children, along with cardiac amyloidosis, which is more commonly seen in progressive multiple myeloma patients and the elderly.

On gross pathological examination, they are solid, sharply circumscribed and pale yellow-tan in colour. 90% are unilateral (arising in one ovary, the other is unaffected). The tumours can vary in size from less than to . Borderline and malignant Brenner tumours are possible but each are rare.

Balkan endemic nephropathy — also called Danubian endemic familial nephropathy (DEFN) — is a form of interstitial nephritis. It was first identified in the 1920s among several small, discrete communities along the Danube River and its major tributaries, in the modern countries of Croatia, Bosnia and Herzegovina, Serbia, Romania and Bulgaria.