Physical expression of nemaline myopathy varies greatly, but weakness is usually concentrated in the proximal muscles, particularly respiratory, bulbar and trunk muscles. People with severe NM show obvious symptoms at birth, while those with intermediate or mild NM may initially appear unaffected. Babies with NM are frequently observed to be "floppy" and hypotonic. Children born with NM often gain strength as they grow, though the effect of muscle weakness on body features may become more evident with time. Adults with NM typically have a very slender physique.

Bulbar (throat) muscle weakness is a main feature of nemaline myopathy. Most individuals with severe NM are unable to swallow and receive their nutrition through feeding tubes. Most people with intermediate and mild NM take some or all of their nutrition orally. Bulbar muscle impairment may also lead to difficulty with communication. People with NM often have hypernasal speech as a result of poor closure of the velopharyngeal port (between the soft palate and the back of the throat). Communicative skills may be enhanced through speech therapy, oral prosthetic devices, surgery, and augmentative communication devices. Individuals with NM are usually highly sociable and intelligent, with a great desire to communicate.

As a result of lower motor neurone degeneration, the symptoms of PMA include:

- atrophy

- fasciculations

- muscle weakness

Some patients have symptoms restricted only to the arms or legs (or in some cases just one of either). These cases are referred to as "Flail Arm" (FA) or "Flail Leg" (FL) and are associated with a better prognosis.

In contrast to amyotrophic lateral sclerosis or primary lateral sclerosis, PMA is distinguished by the "absence" of:

- brisk reflexes

- spasticity

- Babinski's sign

- Emotional lability

Diabetic neuropathy affects all peripheral nerves including sensory neurons, motor neurons, but rarely affects the autonomic nervous system. Therefore, diabetic neuropathy can affect all organs and systems, as all are innervated. There are several distinct syndromes based on the organ systems and members affected, but these are by no means exclusive. A patient can have sensorimotor and autonomic neuropathy or any other combination. Signs and symptoms vary depending on the nerve(s) affected and may include symptoms other than those listed. Symptoms usually develop gradually over years.

Symptoms may include the following:

- Trouble with balance

- Numbness and tingling of extremities

- Dysesthesia (abnormal sensation to a body part)

- Diarrhea

- Erectile dysfunction

- Urinary incontinence (loss of bladder control)

- Facial, mouth and eyelid drooping

- Vision changes

- Dizziness

- Muscle weakness

- Difficulty swallowing

- Speech impairment

- Fasciculation (muscle contractions)

- Anorgasmia

- Retrograde ejaculation (in males)

- Burning or electric pain

3 affected domains of neurological function:

- Cerebral hemisphere (15%)

- Cranial Nerves (35%)

- Spinal cord and roots (60%)

Signs reported

- headache

- mental status change

- confusion

- cognitive impairment

- seizures

- hemiparesis

- gait instability

Other symptoms that are less common are dementia, autonomic dysfunction, cranial nerve abnormalities, spinal symptoms such as limb weakness and paresthesia, and bowel and bladder dysfunction. Diplopia is the most common symptom of cranial nerve dysfunction. Trigeminal sensory or motor loss, cochlear dysfunction, and optic neuropathy are also common findings. Spinal signs and symptoms include weakness, dermatomal or segmental sensory loss, and pain in the neck, back, or following radicular patterns.

Diabetic neuropathies are nerve damaging disorders associated with diabetes mellitus. These conditions are thought to result from a diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum) in addition to macrovascular conditions that can accumulate in diabetic neuropathy. Relatively common conditions which may be associated with diabetic neuropathy include third, fourth, or sixth cranial nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy.

Hereditary folate malabsorption (HFM - OMIM #229050) is a rare autosomal recessive disorder caused by loss-of-function mutations in the proton-coupled folate transporter (PCFT) gene, resulting in systemic folate deficiency and impaired delivery of folate to the brain.

Affected infants present within a few months after birth with failure to thrive and severe folate deficiency manifested as macrocytic anemia and developmental delays. There can be (i) pancytopenia, (ii) diarrhea and/or mucositis and/or (iii) immune deficiency due to T-cell dysfunction and hypoimmunoglobulinemia resulting in pneumonia usually due to Pneumocystis jirovecii. Recently, several infants with the immune deficiency syndrome were described. Untreated, or with inadequate treatment, there are progressive systemic and neurological signs with a spectrum of manifestations including seizures that are often intractable. Females with HFM are fertile and, if folate sufficient during pregnancy, have normal offspring. Subjects that carry one mutated PCFT allele are normal. The genomic and clinical features of HFM were recently reviewed.

Neoplastic or malignant meningitis, also called meningitis carcinomatosa and leptomeningeal carcinomatosis, is the development of meningitis due to infiltration of the subarachnoid space by cancerous cells. Malignant cells come from primary cancer such as breast cancer or from a primary brain tumor like medulloblastoma. Neoplastic Meningitis (NM) was first reported in the 1870s with the most common cause being breast cancer, lung cancer, and malignant melanoma.

Most patients with thin basement membrane disease are incidentally discovered to have microscopic hematuria on urinalysis. The blood pressure, kidney function, and the urinary protein excretion are usually normal. Mild proteinuria (less than 1.5 g/day) and hypertension are seen in a small minority of patients. Frank hematuria and loin pain should prompt a search for another cause, such as kidney stones or loin pain-hematuria syndrome. Also, there are no systemic manifestations, so presence of hearing impairment or visual impairment should prompt a search for hereditary nephritis such as Alport syndrome.

Thin basement membrane disease (TBMD, also known as "benign familial hematuria" and "thin basement membrane nephropathy" or TBMN) is, along with IgA nephropathy, the most common cause of asymptomatic hematuria. The only abnormal finding in this disease is a thinning of the basement membrane of the glomeruli in the kidneys. Its importance lies in the fact that it has a benign prognosis, with patients maintaining a normal kidney function throughout their lives.

Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.

Common proteinopathies that are found in FTLD include the accumulation of Tau proteins and TARDBPs. Mutations in the C9orf72 gene have been established as a major genetic contribution of FTLD, although defects in the GRN and MAPT genes are also associated with it.

The first symptom of CJD is usually rapidly progressive dementia, leading to memory loss, personality changes, and hallucinations. Myoclonus (jerky movements) typically occurs in 90% of cases, but may be absent at initial onset. Other frequently occurring features include anxiety, depression, paranoia, obsessive-compulsive symptoms, and psychosis. This is accompanied by physical problems such as speech impairment, balance and coordination dysfunction (ataxia), changes in gait, rigid posture, and seizures. In most patients, these symptoms are accompanied by involuntary movements and the appearance of an atypical, diagnostic electroencephalogram tracing. The duration of the disease varies greatly, but sporadic (non-inherited) CJD can be fatal within months or even weeks. Most victims die six months after initial symptoms appear, often of pneumonia due to impaired coughing reflexes. About 15% of patients survive for two or more years.

The symptoms of CJD are caused by the progressive death of the brain's nerve cells, which is associated with the build-up of abnormal prion protein molecules forming amyloids. When brain tissue from a CJD patient is examined under a microscope, many tiny holes can be seen where whole areas of nerve cells have died. The word "spongiform" in "transmissible spongiform encephalopathies" refers to the sponge-like appearance of the brain tissue.

There are 3 main histological subtypes found at post-mortem:

- FTLD-tau is characterised by tau positive inclusions often referred to as Pick-bodies. Examples of FTLD-tau include; Pick's disease, corticobasal degeneration, progressive supranuclear palsy.

- FTLD-TDP (or FTLD-U ) is characterised by ubiquitin and TDP-43 positive, tau negative, FUS negative inclusions. The pathological histology of this subtype is so diverse it is subdivided into four subtypes based on the detailed histological findings:

Two physicians independently categorized the various forms of TDP-43 associated disorders. Both classifications were considered equally valid by the medical community, but the physicians in question have jointly proposed a compromise classification to avoid confusion.

- FTLD-FUS; which is characterised by FUS positive cytoplasmic inclusions, intra nuclear inclusions, and neuritic threads. All of which are present in the cortex, medulla, hippocampus, and motor cells of the spinal cord and XIIth cranial nerve.

Dementia lacking distinctive histology (DLDH) is a rare and controversial entity. New analyses have allowed many cases previously described as DLDH to be reclassified into one of the positively defined subgroups.

Symptoms include:

1. yellow-brown, banana-shaped fibers

2. caviar-like papules

3. brown-grey or blue-black hyper-pigmentation

The majority of the lesions will be seen on areas of the body that get the most sun.

Ochronosis is a syndrome caused by the accumulation of homogentisic acid in connective tissues. It was first described by Rudolf Virchow in 1865. The condition was named after the yellowish (ocher-like) discoloration of the tissue seen on microscopic examination. However, macroscopically the affected tissues appear bluish grey because of a light-scattering phenomenon known as the Tyndall effect. The condition is most often associated with alkaptonuria but can occur from exogenous administration of phenol complexes like hydroquinone.

It can present with the following:

- severe burning pain

- lacrimation

- photophobia

- blepharospasm

- swelling of palpebral conjunctiva

- retrotarsal folds

Creutzfeldt–Jakob disease (CJD) is a universally fatal brain disorder. Early symptoms include memory problems, behavioral changes, poor coordination, and visual disturbances. Later dementia, involuntary movements, blindness, weakness, and coma occur. About 90% of people die within a year of diagnosis.

CJD is believed to be caused by a protein known as a prion. Infectious prions are misfolded proteins that can cause normally folded proteins to become misfolded. Most cases occur spontaneously, while about 7.5% of cases are inherited from a person's parents in an autosomal dominant manner. Exposure to brain or spinal tissue from an infected person may also result in spread. There is no evidence that it can spread between people via normal contact or blood transfusions. Diagnosis involves ruling out other potential causes. An electroencephalogram, spinal tap, or magnetic resonance imaging may support the diagnosis.

There is no specific treatment. Opioids may be used to help with pain, while clonazepam or sodium valproate may help with involuntary movements. CJD affects about one per million people per year. Onset is typically around 60 years of age. The condition was first described in 1920. It is classified as a type of transmissible spongiform encephalopathy. CJD is different from bovine spongiform encephalopathy (mad cow disease) and variant Creutzfeldt–Jakob disease (vCJD).

Protein C deficiency is a rare genetic trait that predisposes to thrombotic disease. It was first described in 1981. The disease belongs to a group of genetic disorders known as thrombophilias. Protein C deficiency is associated with an increased incidence of venous thromboembolism (relative risk 8–10), whereas no association with arterial thrombotic disease has been found.

EPP usually presents in childhood with the most common mode of presentation as acute photosensitivity of the skin. It affects areas exposed to the sun and tends to be intractable. A few minutes of exposure to the sun induces pruritus, erythema, swelling and pain. Longer periods of exposure may induce second degree burns. After repetitive exposure, patients may present with lichenification, hypopigmentation, hyperpigmentation and scarring of the skin.

EPP usually first presents in childhood, and most often affects the face and the upper surfaces of the arms, hands, and feet and the exposed surfaces of the legs. Most patients, if the EPP is not as severe, manifest symptoms with onset of puberty when the male and female hormone levels elevate during sexual development and maintenance. More severe EPP can manifest in infancy. EPP can be triggered through exposure to sun even though the patient is behind glass. Even the UV emissions from arc welding with the use of full protective mask have been known to trigger EPP. EPP can also manifest between the ages of 3 and 6.

Prolonged exposure to the sun can lead to edema of the hands, face, and feet, rarely with blistering and petechiae. Skin thickening can sometimes occur over time.

People with EPP are also at increased risk to develop gallstones. One study has noted that EPP patients suffer from vitamin D deficiency.

Erythropoietic protoporphyria (EPP) is a form of porphyria, which varies in severity and can be very painful. It arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the erythrocytes, plasma, skin and liver. The severity varies significantly from individual to individual.

A clinically similar form of porphyria, known as X-Linked dominant protoporphyria, was identified in 2008.

VHSV is a hemorrhagic disease, meaning it causes bleeding. Internally,

the virus can cause petechial hemorrhaging (tiny spots of blood) in internal

muscle tissue, and petechial or severe hemorrhaging in internal organs and

other tissues. Internal hemorrhaging can be observed as red spots inside

a dead fish, particularly around the kidney, spleen, and intestines, as

well as the swim bladder, which would normally have a clear membrane.

The liver may be pale, mottled with red hyperemic areas, the kidney

may be swollen and unusually red, the spleen may be swollen, and the digestive

tract may be empty.

External signs are not always present, but if they are, hemorrhaging on the

skin's surface can appear as anywhere from tiny red dots (petechiae) to

large red patches.

Generally, the areas affected are exposed skin not usually protected by clothing; however it can also occur in areas covered by clothing. Areas constantly subjected to the sun's rays may only be slightly affected if at all. People with extreme cases will also have reactions to light bulbs that emit a UV wavelength (any bulb that is not an LED). Parts of the body only thinly covered can also potentially be subjected to an outbreak.

Life with SU can be difficult. Patients are subject to constant itching and pain, as within minutes of the initial exposure to UV radiation a rash will appear. The urticarial reaction begins in the form of pruritus, later progressing to erythema and edema in the exposed areas of the skin. If vast areas of the body are affected, the loss of fluid into the skin could lead to light-headedness, headache, nausea, and vomiting. Extremely rarely, patients have been reported to experience an increase in heart rate that can cause a stroke or heart attack due to the body cavity swelling. Other rare side effects can be bronchospasm and glucose instability issues. Also, if a large area of the body is suddenly exposed the person may be subject to an anaphylactic reaction. Once free of exposure, the rash will usually fade away within several hours; rare and extreme cases can take a day or two to normalize depending on severity of the reaction.

Living fish afflicted with VHS may appear listless or limp, hang just

beneath the surface, or swim very abnormally, such as constant flashing

circling due to the tropism of the virus for the brain.

External signs may include darker coloration, exophthalmia ("pop eye"),

pale or red-dotted gills, sunken eyes, and bleeding around orbits (eye sockets) and

at base of fins.

Genetics researchers at the Lake Erie Research Center at the University of Toledo are developing a test that will speed diagnosis from a month to a matter of hours.