Familial dysautonomia, which affects the development and survival of sensory, sympathetic, and parasympathetic neurons, is a debilitating disorder present from birth. Neuronal degeneration progresses throughout life. Affected individuals have gastrointestinal dysfunction, autonomic crises (i.e., hypertensive vomiting attacks), recurrent pneumonia, altered pain sensitivity, altered temperature perception, and blood pressure instability. Hypotonia contributes to delay in acquisition of motor milestones. Optic neuropathy results in progressive vision loss. Older individuals often have a broad-based and ataxic gait that deteriorates over time. Developmental delay / intellectual disability occur in about 21% of individuals. Life expectancy is decreased.

Adult Refsum disease (ARD is associated with elevated plasma phytanic acid levels, late childhood-onset (or later) retinitis pigmentosa, and variable combinations of anosmia, polyneuropathy, deafness, ataxia, and ichthyosis. Onset of symptoms ranges from age seven months to older than age 50 years. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems that develop later in life.

Hereditary thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome (USS), is a rare autosomal recessive thrombotic microangiopathy (TMA). Clinically, acute phases of TTP are defined by microangiopathic mechanical hemolytic anemia, severe thrombocytopenia, and visceral ischemia. Hereditary TTP makes up 5% of TTP cases and is caused mostly by biallelic mutation in the ADAMTS13 gene, or in very rare cases, by monoallelic ADAMTS13 mutation associated with a cluster of single-nucleotide polymorphisms (SNPs); most cases of all TTP (95%) are acquired via an autoimmune mechanism (see 188030). Hereditary TTP is more frequent among child-onset TTP compared with adult-onset TTP, and its clinical presentation is significantly different as a function of its age of onset. Child-onset TTP usually starts in the neonatal period with hematological features and severe jaundice. In contrast, almost all cases of adult-onset hereditary TTP are unmasked during the first pregnancy of a woman whose disease was silent during childhood (summary by Joly et al., 2018).

Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation in connective tissues, such as cartilage and the lining of blood vessels, which provide strength and flexibility to structures throughout the body. The signs and symptoms of SLE vary among affected individuals, and can involve many organs and systems, including the skin, joints, kidneys, lungs, central nervous system, and blood-forming (hematopoietic) system. SLE is one of a large group of conditions called autoimmune disorders that occur when the immune system attacks the body's own tissues and organs.\n\nSLE may first appear as extreme tiredness (fatigue), a vague feeling of discomfort or illness (malaise), fever, loss of appetite, and weight loss. Most affected individuals also have joint pain, typically affecting the same joints on both sides of the body, and muscle pain and weakness. Skin problems are common in SLE. A characteristic feature is a flat red rash across the cheeks and bridge of the nose, called a "butterfly rash" because of its shape. The rash, which generally does not hurt or itch, often appears or becomes more pronounced when exposed to sunlight. Other skin problems that may occur in SLE include calcium deposits under the skin (calcinosis), damaged blood vessels (vasculitis) in the skin, and tiny red spots called petechiae. Petechiae are caused by a shortage of cells involved in clotting (platelets), which leads to bleeding under the skin. Affected individuals may also have hair loss (alopecia) and open sores (ulcerations) in the moist lining (mucosae) of the mouth, nose, or, less commonly, the genitals.\n\nPeople with SLE have episodes in which the condition gets worse (exacerbations) and other times when it gets better (remissions). Overall, SLE gradually gets worse over time, and damage to the major organs of the body can be life-threatening.\n\nAbout a third of people with SLE develop kidney disease (nephritis). Heart problems may also occur in SLE, including inflammation of the sac-like membrane around the heart (pericarditis) and abnormalities of the heart valves, which control blood flow in the heart. Heart disease caused by fatty buildup in the blood vessels (atherosclerosis), which is very common in the general population, is even more common in people with SLE. The inflammation characteristic of SLE can also damage the nervous system, and may result in abnormal sensation and weakness in the limbs (peripheral neuropathy); seizures; stroke; and difficulty processing, learning, and remembering information (cognitive impairment). Anxiety and depression are also common in SLE.

A rare renal disease characterized by the association of X-linked Alport syndrome (glomerular nephropathy, sensorineural deafness and ocular anomalies) and benign proliferation of visceral smooth muscle cells along the gastrointestinal, respiratory, and female genital tracts and clinically manifests with dysphagia, dyspnea, cough, stridor, postprandial vomiting, retrosternal or epigastric pain, recurrent pneumonia, and clitoral hypertrophy in females.

A rare immune complex-mediated vasculitis characterized by the presence of circulating cryoprecipitable immune complexes in the serum, manifesting clinically with the classical triad of purpura, weakness and arthralgia.