The symptoms of pernicious anemia come on slowly. Untreated, it can lead to neurological complications, and in serious cases, death. Many of the signs and symptoms are due to anemia itself, when anemia is present. Symptoms may consist of the triad of tingling or other skin sensations (paresthesia), tongue soreness (glossitis), and fatigue and general weakness. It presents with a number of further common symptoms, including depressive mood, low-grade fevers, diarrhea, dyspepsia, weight loss, neuropathic pain, jaundice, sores at the corner of the mouth (angular cheilitis), a look of exhaustion with pale and dehydrated or cracked lips and dark circles around the eyes, as well as brittle nails, and thinning and early greying of the hair. Because PA may affect the nervous system, symptoms may also include difficulty in proprioception, memory changes, mild cognitive impairment (including difficulty concentrating and sluggish responses, colloquially referred to as brain fog), and even psychoses, impaired urination, loss of sensation in the feet, unsteady gait, difficulty in walking, muscle weakness and clumsiness. Anemia may also lead to tachycardia (rapid heartbeat), cardiac murmurs, a yellow waxy pallor, altered blood pressure (low or high), and a shortness of breath (known as "the sighs"). The deficiency also may present with thyroid disorders. In severe cases, the anemia may cause evidence of congestive heart failure. A complication of severe chronic PA is subacute combined degeneration of spinal cord, which leads to distal sensory loss (posterior column), absent ankle reflex, increased knee reflex response, and extensor plantar response. Other than anemia, hematological symptoms may include cytopenias, intramedullary hemolysis, and pseudothrombotic microangiopathy. Pernicious anemia can contribute to a delay in physical growth in children, and may also be a cause for delay in puberty for adolescents.

Vitamin B deficiency anemia, of which pernicious anemia is a type, is a disease in which not enough red blood cells are present due to a lack of vitamin B. The most common initial symptom is feeling tired. Other symptoms may include shortness of breath, pale skin, chest pain, numbness in the hands and feet, poor balance, a smooth red tongue, poor reflexes, depression and confusion. Without treatment some of these problems may become permanent.

Although pernicious anemia technically refers to cases resulting from not enough intrinsic factor, it is often used to describe all cases of anemia due to not enough vitamin B. Lack of intrinsic factor is most commonly due to an autoimmune attack on the cells that create it in the stomach. It can also occur following the surgical removal of part of the stomach or from an inherited disorder. Other causes of low vitamin B include not enough dietary intake (such as in a vegan diet), celiac disease, or tapeworm infection. When suspected, diagnosis is made by blood and, occasionally, bone marrow tests. Blood tests may show fewer but larger red blood cells, low numbers of young red blood cells, low levels of vitamin B, and antibodies to intrinsic factor.

Pernicious anemia, due to lack of intrinsic factor, is not preventable. Vitamin B deficiency due to other causes may be prevented with a balanced diet or with supplements. Pernicious anemia can be easily treated with either injections or pills of vitamin B. If the symptoms are severe, injections are typically recommended initially. For those who have trouble swallowing pills, a nasal spray is available. Often, treatment is lifelong.

Pernicious anemia due to autoimmune problems occurs in about one per 1000 people. Among those over the age of 60, about 2% have the condition. It more commonly affects people of northern European descent. Women are more commonly affected than men. With proper treatment, most people live normal lives. Due to a higher risk of stomach cancer, those with pernicious anemia should be checked regularly for this. The first clear description was by Thomas Addison in 1849. The term "pernicious" means "deadly", and was used as before the availability of treatment the disease was often fatal.

Defined as those seen in any macrocytic, megaloblastic anemia:

- Anemia: causing fatigue, conjuctival pallor, pale complexion, and in some cases, a mild icterus (yellowing of the eye).

- Glossitis ("shiny tongue"): shiny, glossy tongue.

- Cheilosis (stomatitis): Inflammation of the edges of the lips and the oral mucosa.

- Tabes dorsalis ("subacute combined degeneration of the spinal cord"): This involves the posterior section of the spinal cord and therefore involves proprioception (sense of position), touch, sense of vibration and in severe cases the lateral corticospinal tract, causing spastic paralysis of the limbs.

- Peripheral neuropathy: tingling sensation in the arms and legs.

- Pancytopenia: decreased number of blood cells of all lineages (RBCs, leucocytes, platelets), due to decreased bone marrow production.

- Methylmalonyl CoA-emia: defined as blood having an unusually high concentration of methylmalonyl CoA.

- Peripheral findings such as hypersegmented neutrophils and large RBCs on high field view of the blood smears.

- Laboratory findings indicating increased MCV (Mean Corpuscular Volume), decreased Hgb/Hct (indicating anemia), and decreased value of vitamin B in the blood.

- Proteinuria: protein found in the urine detected by analysis or by dipstick.

- Reversal of all symptoms except neurological symptoms, by IV injection of vitamin B.

- Schilling test indicating no radioactive vitamin B in the urine. (This test has dropped out of favor and should not be tried in patients with any form of renal failure).

Imerslund–Gräsbeck syndrome, is a rare autosomal recessive, familial form of vitamin B deficiency caused by malfunction of the ""Cubam"" receptor located in the terminal ileum. This receptor is composed of two proteins, amnionless (AMN), and cubilin. A defect in either of these protein components can cause this syndrome. This is a rare disease, with a prevalence about 1 in 200,000, and is usually seen in patients of European ancestry.

Vitamin B is an important vitamin needed for bone marrow functioning, the deficit of which causes decreased marrow output and anemia. Vitamin B has two forms, one of which, along with folate, is important in DNA synthesis. Vitamin B is sensitive to acid deformation in the stomach, so a molecule called haptocorrin (R-factor), protects it in the stomach. In the small bowel, a molecule named intrinsic factor (IF), allows vitamin B to be absorbed in the ileum. IGS is caused by a mutation in the receptors located in the terminal portion of ileum. This is a very rare, and unlikely cause of vitamin B deficiency but is a cause nonetheless.

Pearson syndrome is a mitochondrial disease characterized by sideroblastic anemia and exocrine pancreas dysfunction. Other clinical features are failure to thrive, pancreatic fibrosis with insulin-dependent diabetes and exocrine pancreatic deficiency, muscle and neurologic impairment, and, frequently, early death. It is usually fatal in infancy. The few patients who survive into adulthood often develop symptoms of Kearns-Sayre syndrome.

It is caused by a deletion in mitochondrial DNA. Pearson syndrome is very rare, less than hundred cases have been reported in medical literature worldwide.

The syndrome was first described by pediatric hematologist and oncologist Howard Pearson in 1979; the deletions causing it were discovered a decade later.

1. Blood. With Pearson Syndrome, the bone marrow fails to produce white blood cells called neutrophils. The syndrome also leads to anemia, low platelet count, and aplastic anemia It may be confused with transient erythroblastopenia of childhood.

2. Pancreas. Pearson Syndrome causes the exocrine pancreas to not function properly because of scarring and atrophy

Individuals with this condition have difficulty absorbing nutrients from their diet which leads to malabsorption. infants with this condition generally do not grow or gain weight.

Bloom syndrome is characterized by genome instability. The most prominent features include short stature and a rash on the face that develops early in life when exposed to the sun. The skin rash is erythematous, telangiectatic, infiltrated, and scaly, it can appear across the nose, on the cheeks and around the lips. As well as these areas the rash will develop on any other sun-exposed areas including, the backs of the hands and neck. Other clinical features include a high-pitched voice; distinct facial features, including a long, narrow face, micrognathism, and prominent nose and ears; pigmentation changes of the skin including hypo-pigmented and hyper-pigmented areas, cafe-au-lait spots, and telangiectasias (dilated blood vessels), which can appear on the skin and eyes. Moderate immune deficiency, characterized by deficiency in certain immunoglobulin classes has also been related to BS, leading to recurrent pneumonia and ear infections. Most individuals with Bloom syndrome are born with a low birth weight. Hypogonadism is characterized by a failure to produce sperm, hence infertility in males, and premature cessation of menses (premature menopause), hence sub-fertility in females. However, several women with Bloom syndrome have had children. The most serious and common complication of Bloom syndrome is cancer. Other complications of the disorder include chronic obstructive lung disease, diabetes, and learning disabilities. There is no evidence that mental retardation is more common in Bloom syndrome than in other people. People with Bloom Syndrome have a shortened life expectancy; the average life span is approximately 27 years. Bloom syndrome shares some features with Fanconi anemia possibly because there is overlap in the function of the proteins mutated in this related disorder.

Bloom syndrome (often abbreviated as BS in literature), also known as Bloom-Torre-Machacek syndrome, is a rare autosomal recessive disorder characterized by short stature, predisposition to the development of cancer and genomic instability. BS is caused by mutations in the BLM gene leading to mutated DNA helicase protein formation. Cells from a person with Bloom syndrome exhibit a striking genomic instability that includes excessive crossovers between homologous chromosomes and sister chromatid exchanges (SCEs). The condition was discovered and first described by New York dermatologist Dr. David Bloom in 1954.

Autoimmune polyendocrine syndrome type 1 symptoms and signs include the following:

- Hypoparathyroidism

- Hypogonadism

- Vitiligo

- Alopecia

- Malabsorption

- Anemia

- Cataract

- Adrenal hyperplasia

ABCD syndrome is the acronym for albinism, black lock, cell migration disorder of the neurocytes of the gut, and sensorineural deafness. It has been found to be caused by mutation in the endothelin B receptor gene (EDNRB).

ABCD syndrome is defined as albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness. It was initially misdiagnosed and later discovered that a homozygous mutation in the EDNRB gene causes ABCD syndrome. This helped scientists discover that it is the same as type IV Waardenburg syndrome, also known as Shah-Waardenburg syndrome.

Rotor syndrome has many features in common with Dubin–Johnson syndrome, an exception being that the liver cells are not pigmented. The main symptom is a non-itching jaundice. There is a rise in bilirubin in the patient's serum, mainly of the conjugated type.

It can be differentiated from Dubin–Johnson syndrome in the following ways:

It has been suggested that Rotor Syndrome may exacerbate toxic side effects of the drug irinotecan.

Rotor syndrome, also called Rotor type hyperbilirubinemia, is a rare, relatively benign autosomal recessive bilirubin disorder. It is a distinct, yet similar disorder to Dubin–Johnson syndrome — both diseases cause an increase in conjugated bilirubin.

Autoimmune polyendocrine syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy/dysplasia (APECED), autoimmune polyglandular syndrome type 1, Whitaker syndrome, or candidiasis-hypoparathyroidism–Addison's disease syndrome, is a subtype of autoimmune polyendocrine syndrome (autoimmune polyglandular syndrome) in which multiple endocrine glands dysfunction as a result of autoimmunity. It is a genetic disorder inherited in autosomal recessive fashion due to a defect in the "AIRE" gene (autoimmune regulator), which is located on chromosome 21 and normally confers immune tolerance.

The syndrome is a rare clinical disorder.

- Physical

- Overgrowth

- Accelerated skeletal maturation

- Dysmorphic facial features

- Prominent eyes

- Bluish sclerae

- Coarse eyebrows

- Upturned nose

- Radiologic examination

- Accelerated osseous maturation

- Phalangeal abnormalities

- Tubular thinning of the long bones

- Skull abnormalities

- Mental

- Often associated with intellectual disability (of variable degree)

Ballantyne syndrome has several characteristics:

- edema, always a key feature

- albuminuria of the mother, usually mild

- preeclampsia, unusual

The fetal symptoms are related to fluid retention, including ascites and polyhydramnios.

Fetal hydrops suggests the presence of an important and probably fatal fetal pathology.

It can be associated with twin-to-twin transfusion syndrome.

Mirror syndrome or triple oedema or Ballantyne syndrome is a rare disorder affecting pregnant women. It describes the unusual association of fetal

and placental hydrops with maternal preeclampsia.

The name "mirror syndrome" refers to the similarity between maternal oedema and fetal hydrops. It was first described in 1892 by John William Ballantyne.

One of the most prominent and visible symptoms of Nevo Syndrome is the prenatal overgrowth, which continues into the infant and toddler stage. This excessive weight gain can be attributed to the low concentrations of growth hormone and insulin growth factor that are normally present to regulate weight gain. Other common symptoms associated with Nevo Syndrome are the outward wrist-drop, edema in hands and feet, undescended testes, low-set ears, hypotonia, the presence of low muscle tone in children, and long tapered fingers, and a highly arched palate.

Marshall-Smith Syndrome, discovered in 1971 (Marshall, Graham, Scott, Boner, & Smith), is characterized by unusual accelerated skeletal maturation (usually starting before birth) and symptoms like conspicuous physical characteristics, respiratory difficulties, and mental retardation. Cases described in the literature show a clinical variability regarding related symptoms. For instance, respiratory difficulties are ranging from absent to severe difficulties.

Oculocerebrorenal syndrome (also called Lowe syndrome) is a rare X-linked recessive disorder characterized by congenital cataracts, hypotonia, intellectual disability, proximal tubular acidosis, aminoaciduria, and low-molecular-weight proteinuria. Lowe syndrome can be considered a cause of Fanconi syndrome (bicarbonaturia, renal tubular acidosis, potassium loss, and sodium loss).

The key affected features of this condition are described in its name.

Scalp: There are raised nodules over the posterior aspect of the scalp, covered by scarred non-hair bearing skin.

Ears: The shape of the pinnae is abnormal, with the superior edge of the pinna being turned over more than usual. The size of the tragus, antitragus and lobule may be small.

Nipples: The nipples are absent or rudimentary. The breasts may be small or virtually absent.

Other features of the condition include:

Dental abnormalities: missing or widely spaced teeth

Syndactyly: toes or fingers may be partially joined proximally

Renal abnormalities: renal hypoplasia, pyeloureteral duplication

Eye abnormalities: Cataract, coloboma of the iris and asymmetric pupils.

Café au lait spots are usually present at birth, permanent, and may grow in size or increase in number over time.

Cafe au lait spots are themselves benign and do not cause any illness or problems. However, they may be associated with syndromes such as Neurofibromatosis Type 1 and McCune-Albright syndrome.

The size and shape of the spots do not have any meaning or implications with regards to diagnosis of associated syndromes.

Causes for similar symptoms include

- Various inborn metabolic disorders

- Viral encephalitis

- Drug overdose or poisoning

- Head trauma

- Liver failure due to other causes

- Meningitis

- Kidney failure

- Shaken baby syndrome

Reye syndrome progresses through five stages:

- Stage I

- Rash on palms of hands and feet

- Persistent, heavy vomiting that is not relieved by not eating

- Generalized lethargy

- Confusion

- Nightmares

- No fever usually present

- Headaches

- Stage II

- Stupor

- Hyperventilation

- Fatty liver (found by biopsy)

- Hyperactive reflexes

- Stage III

- Continuation of Stage I and II symptoms

- Possible coma

- Possible cerebral edema

- Rarely, respiratory arrest

- Stage IV

- Deepening coma

- Dilated pupils with minimal response to light

- Minimal but still present liver dysfunction

- Stage V

- Very rapid onset following stage IV

- Deep coma

- Seizures

- Multiple organ failure

- Flaccidity

- Hyperammonemia (above 300 mg/dL of blood)

- Death

People with Aarskog-Scott syndrome often have distinctive facial features, such as widely spaced eyes (hypertelorism), a small nose, a long area between the nose and mouth (philtrum), and a widow's peak hairline. They frequently have mild to moderate short stature during childhood, but their growth usually catches up with that of their peers during puberty. Hand abnormalities are common in this syndrome and include short fingers (brachydactyly), curved pinky fingers (fifth finger clinodactyly), webbing of the skin between some fingers (cutaneous syndactyly), and a single crease across the palm. Other abnormalities in people with Aarskog-Scott syndrome include heart defects and a split in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate).

Most males with Aarskog-Scott syndrome have a shawl scrotum, in which the scrotum surrounds the penis instead of hanging below. Less often, they have undescended testes (cryptorchidism) or a soft out-pouching around the belly-button (umbilical hernia) or in the lower abdomen (inguinal hernia).

The intellectual development of people with Aarskog-Scott syndrome varies widely. Some may have mild learning and behavior problems, while others have normal intelligence. In rare cases, severe intellectual disability has been reported.