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.

Megaloblastic anemia (or megaloblastic anaemia) is an anemia (of macrocytic classification) that results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis.

Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias.

The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically a deficiency of vitamin B and/or folic acid. Vitamin B deficiency alone will not cause the syndrome in the presence of sufficient folate, as the mechanism is loss of B dependent folate recycling, followed by folate-deficiency loss of nucleic acid synthesis (specifically thymine), leading to defects in DNA synthesis. Folic acid supplementation in the absence of vitamin B prevents this type of anemia (although other vitamin B-specific pathologies may be present). Loss of micronutrients may also be a cause. Copper deficiency resulting from an excess of zinc from unusually high oral consumption of zinc-containing denture-fixation creams has been found to be a cause.

Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites that poison DNA production directly, such as some chemotherapeutic or antimicrobial agents (for example azathioprine or trimethoprim).

The pathological state of megaloblastosis is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow and also by hypersegmented neutrophils (those exhibiting five or more nuclear lobes ("segments"), with up to four lobes being normal). These hypersegmented neutrophils can be detected in the peripheral blood (using a diagnostic smear of a blood sample).

The blood film can point towards vitamin deficiency:

- Decreased red blood cell (RBC) count and hemoglobin levels

- Increased mean corpuscular volume (MCV, >100 fL) and mean corpuscular hemoglobin (MCH)

- Normal mean corpuscular hemoglobin concentration (MCHC, 32–36 g/dL)

- The reticulocyte count is decreased due to destruction of fragile and abnormal megaloblastic erythroid precursor.

- The platelet count may be reduced.

- Neutrophil granulocytes may show multisegmented nuclei ("senile neutrophil"). This is thought to be due to decreased production and a compensatory prolonged lifespan for circulating neutrophils, which increase numbers of nuclear segments with age.

- Anisocytosis (increased variation in RBC size) and poikilocytosis (abnormally shaped RBCs).

- Macrocytes (larger than normal RBCs) are present.

- Ovalocytes (oval-shaped RBCs) are present.

- Howell-Jolly bodies (chromosomal remnant) also present.

Blood chemistries will also show:

- An increased lactic acid dehydrogenase (LDH) level. The isozyme is LDH-2 which is typical of the serum and hematopoetic cells.

- Increased homocysteine and methylmalonic acid in Vitamin B deficiency

- Increased homocysteine in folate deficiency

Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.

Bone marrow (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic hyperplasia.

Anemia goes undetected in many people and symptoms can be minor. The symptoms can be related to an underlying cause or the anemia itself.

Most commonly, people with anemia report feelings of weakness or tired, and sometimes poor concentration. They may also report shortness of breath on exertion. In very severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. The patient may have symptoms related to this, such as palpitations, angina (if pre-existing heart disease is present), intermittent claudication of the legs, and symptoms of heart failure.

On examination, the signs exhibited may include pallor (pale skin, lining mucosa, conjunctiva and nail beds), but this is not a reliable sign. There may be signs of specific causes of anemia, e.g., koilonychia (in iron deficiency), jaundice (when anemia results from abnormal break down of red blood cells — in hemolytic anemia), bone deformities (found in thalassemia major) or leg ulcers (seen in sickle-cell disease).

In severe anemia, there may be signs of a hyperdynamic circulation: tachycardia (a fast heart rate), bounding pulse, flow murmurs, and cardiac ventricular hypertrophy (enlargement). There may be signs of heart failure.

Pica, the consumption of non-food items such as ice, but also paper, wax, or grass, and even hair or dirt, may be a symptom of iron deficiency, although it occurs often in those who have normal levels of hemoglobin.

Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced academic performance in children of school age. Restless legs syndrome is more common in those with iron-deficiency anemia.

A dimorphic appearance on a peripheral blood smear occurs when there are two simultaneous populations of red blood cells, typically of different size and hemoglobin content (this last feature affecting the color of the red blood cell on a stained peripheral blood smear). For example, a person recently transfused for iron deficiency would have small, pale, iron deficient red blood cells (RBCs) and the donor RBCs of normal size and color. Similarly, a person transfused for severe folate or vitamin B12 deficiency would have two cell populations, but, in this case, the patient's RBCs would be larger and paler than the donor's RBCs. A person with sideroblastic anemia (a defect in heme synthesis, commonly caused by alcoholism, but also drugs/toxins, nutritional deficiencies, a few acquired and rare congenital diseases) can have a dimorphic smear from the sideroblastic anemia alone. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), indicating a wider-than-normal range of red cell sizes, also seen in common nutritional anemia.

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.

Symptoms of sideroblastic anemia include skin paleness, fatigue, dizziness, and enlarged spleen and liver. Heart disease, liver damage, and kidney failure can result from iron buildup in these organs.

Sideroblastic anemia is typically divided into subtypes based on its cause.

- Hereditary or congenital sideroblastic anemia may be X-linked or autosomal.

GLRX5 has also been implicated.

- Acquired, or secondary, sideroblastic anemia develops after birth and is divided according to its cause.

The term macrocytic is from Greek words meaning "large cell". A macrocytic class of anemia is an "anemia" (defined as blood with an insufficient concentration of hemoglobin) in which the red blood cells (erythrocytes) are larger than their normal volume. The normal erythrocyte volume in humans is about 80 to 100 femtoliters (fL= 10 L). In metric terms the size is given in equivalent cubic micrometers (1 μm = 1 fL). The condition of having erythrocytes which (on average) are too large, is called macrocytosis. In contrast, in microcytic anemia, the erythrocytes are smaller than normal.

In a macrocytic anemia, the larger red cells are always associated with insufficient "numbers" of cells and often also insufficient hemoglobin content per cell. Both of these factors work to the opposite effect of larger cell size, to finally result in a "total blood hemoglobin concentration" that is less than normal (i.e., anemia).

Macrocytic anemia is not a disease in the sense of having a single pathology but, rather, is a condition. As such, it is the class name for a set of pathologies that all produce somewhat the same red blood cell abnormality. Many specific pathologies are known which result in macrocytic-type anemias. Some of these produce slightly different sets of appearances in blood cells that are detectable from red and white cell morphology, and others are only detectable with chemical testing.

Mild macrocytosis is a common finding associated with rapid blood restoration or production, since in general, "fresh" or newly produced red cells (reticulocytes) are larger than the mean (average) size, due to slow shrinkage of normal cells over a normal red cell circulating lifetime. Thus, chronic obstructive pulmonary disease (COPD), in which red cells are rapidly produced in response to low oxygen levels in the blood, often produces mild macrocytosis. Also, rapid blood replacement from the marrow after a traumatic blood loss, or rapid red blood cell turnover from rapid hemolysis (G6PD deficiency), also often produces mild macrocytosis in the associated anemia.

Nutritional anemia refers to the low concentration of hemoglobin due to poor diet. According to the World Health Organization, a hemoglobin concentration below 7.5 mmol/L and 8. mmol/L for women and men, respectively, is considered to be anemic. Thus, anemia can be diagnosed with blood tests. Hemoglobin is used to transport and deliver oxygen in the body. Without oxygen, the human body cannot undergo respiration and create ATP, thereby depriving cells of energy.

Nutritional anemia is caused by a lack of iron, protein, B12, and other vitamins and minerals that needed for the formation of hemoglobin. Folic acid deficiency is a common association of nutritional anemia and iron deficiency anemia is the most common nutritional disorder.

Signs of anemia include cyanosis, jaundice, and easy bruising. In addition, anemic patients may experience difficulties with memory and concentration, fatigue, lightheadedness, sensitivity to temperature, low energy levels, shortness of breath, and pale skin. Symptoms of severe or rapid-onset anemia are very dangerous as the body is unable to adjust to the lack of hemoglobin. This may result in shock and death. Mild and moderate anemia have symptoms that develop slowly over time.[5] If patients believe that they are at risk for or experience symptoms of anemia, they should contact their doctor.

Treatments for nutritional anemia includes replacement therapy is used to elevate the low levels of nutrients.[1] Diet improvement is a way to combat nutritional anemia and this can be done by taking dietary supplements such as iron, folate, and Vitamin B12.[2] These supplements are available over-the-counter however, a doctor may prescribe prescription medicine as needed, depending on the patient’s health needs.

Internationally, anemia caused by iron deficiencies is the most common nutritional disorder. It is the only significantly prevalent nutritional deficiency disorder in industrialized countries. In poorer areas, anemia is worsened by infectious diseases such as HIV/AIDS, tuberculosis, hookworm infestation, and Malaria. In developing countries, about 40% of preschool children and 50% of pregnant women are estimated to be anemic. 20% of maternal deaths can be contributed to anemia. Health consequences of anemia include low pregnancy outcome, impaired cognitive and physical development, increased rate of morbidity, and reduced rate of work in adults.

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Nutritional Anemia has many different causes, each either nutritional or non-nutritional. Nutritional causes are vitamin and mineral deficiencies and non-nutritional causes can be infections. The number one cause of this type of anemia however is iron deficiency.

An insufficient intake of iron, Vitamin B12, and folic acid impairs the bone marrow function.

The lack of iron within a person’s body can also stem from ulcer bacteria. These microbes live in the digestive track and after many years cause ulcer’s in the lining of your stomach or small intestine. Therefore, a high percentage of patients with nutritional anemia may have potential gastrointestinal disorder that causes chronic blood loss. This is common in immunocompromised, elderly, and diabetic people. High blood loss can also come from increases loss of blood during menstruation, childbirth, cancers of the intestines, and a disorder that hinders blood’s ability to coagulate.

Medications can have adverse effects and cause nutritional anemia as well. Medications that stop the absorption of iron in the gut and cause bleeding from the gut (NSAIDs and Aspirin) can be culprits in the development of this condition. Hydrocortisones and valproic acid are also two drugs that cause moderate bleeding from the gut. Amoxicillin and phenytoin are the ability to cause a vitamin B12 deficiency.

Other common causes are thyroid disorders, lead toxcities, infectious diseases (e.g Malaria), Alcoholism, and Vitamin E deficiency.

Symptoms

Symptoms of nutritional anemia can include fatigue and lack of energy. However if symptoms progress, one may experience shortness of breath, rapid pulse, paleness --especially in the hands, eyelids and fingernails---, swelling of ankles, hair loss, lightheadedness, compulsive and atypical cravings, constipation, depression, muscle twitching, numbness, or burning and chest pain.

Those who have nutritional anemia often show little to no symptoms. Often, symptoms can go undetected as mild forms of the anemia have only minor symptoms.

----[1] “Micronutrient deficiencies” World Health Organization. Accessed March 31, 2017. http://www.who.int/nutrition/topics/ida/en/

[2] "Ibid."

[3] "Ibid."

[4] "Ibid"

[5] "Ibid"

[6] "Ibid"

----[1] "Ibid".

[2] “Treatments for Nutritional anemia.” Right Diagnosis. Assessed March 31, 2017. http://www.rightdiagnosis.com/n/nutritional_anemia/treatments.htm

----[1] "Ibid".

[2] “What are the symptoms of anemia?” Health Grades, INC. Accessed March 31, 2017. https://www.healthgrades.com/conditions/anemia--symptoms.

[3] "Ibid."

[4] "Ibid."

[5] "Ibid."

[6] "Ibid"

----[1] "Ibid".

[2] "Ibid".

----[1] "Nutritional Anemia." The Free Dictionary. Accessed March 31, 2017. http://medical-dictionary.thefreedictionary.com/nutritionalanemia.

[2] "Ibid".

[3] "Ibid".

[4] "Ibid".

Nutritional anemia refers to types of anemia that can be directly attributed to nutritional disorders.

Examples include Iron deficiency anemia and pernicious anemia.

It is often discussed in a pediatric context.

Anisocytosis is a medical term meaning that a patient's red blood cells are of unequal size. This is commonly found in anemia and other blood conditions. False diagnostic flagging may be triggered by an elevated WBC count, agglutinated RBCs, RBC fragments, giant platelets or platelet clumps. In addition, it is a characteristic feature of bovine blood.

The red cell distribution width (RDW) is a measurement of anisocytosis and is calculated as a coefficient of variation of the distribution of RBC volumes divided by the mean corpuscular volume (MCV)

Macrocytosis is the enlargement of red blood cells with near-constant hemoglobin concentration, and is defined by a mean corpuscular volume (MCV) of greater than 100 femtolitres (the precise criterion varies between laboratories). The enlarged erythrocytes are called macrocytes or megalocytes (both words have roots meaning "big cell").

No complications arise from macrocytosis itself and a prognosis will be determined from its cause.

Anemia may lead to malaise, pallor and associated symptoms such as palpitations.

Low platelet counts (thrombocytopenia) if present is associated with an increased risk of hemorrhage, bruising and petechiae. Low white blood cell counts (leukocytopenia) if present leads to an increased risk of infections which can be severe.

Congenital hypoplastic anemia (or constitutional aplastic anemia) is a type of aplastic anemia which is primarily due to a congenital disorder.

Associated genes include "TERC", "TERT", "IFNG", "NBS1", "PRF1", and "SBDS".

Examples include:

- Fanconi anemia

- Diamond-Blackfan anemia

Most individuals with G6PD deficiency are asymptomatic.

Symptomatic patients are almost exclusively male, due to the X-linked pattern of inheritance, but female carriers can be clinically affected due to unfavorable lyonization, where random inactivation of an X-chromosome in certain cells creates a population of G6PD-deficient red blood cells coexisting with unaffected red blood cells. A female with one affected X chromosome will show the deficiency in approximately half of her red blood cells. However, in rare cases, including double X-deficiency, the ratio can be much more than half, making the individual almost as sensitive as males.

Red blood cell breakdown (also known as hemolysis) in G6PD deficiency can manifest in a number of ways, including the following:

- Prolonged neonatal jaundice, possibly leading to kernicterus (arguably the most serious complication of G6PD deficiency)

- Hemolytic crises in response to:

- Illness (especially infections)

- Certain drugs (see below)

- Certain foods, most notably broad beans from which the word favism derives

- Certain chemicals

- Diabetic ketoacidosis

- Very severe crises can cause acute kidney failure

Favism may be formally defined as a hemolytic response to the consumption of fava beans, also known as broad beans. Important to note is that all individuals with favism show G6PD deficiency, but not all individuals with G6PD deficiency show favism. The condition is known to be more prevalent in infants and children, and G6PD genetic variant can influence chemical sensitivity. Other than this, the specifics of the chemical relationship between favism and G6PD are not well understood.

Carriers of the underlying mutation do not show any symptoms unless their red blood cells are exposed to certain triggers, which can be of three main types:

- Foods (fava beans is the hallmark trigger for G6PD mutation carriers),

- Medicines and other chemicals such as those derived from quinine (see below), or

- Stress from a bacterial or viral infection.

In order to avoid the hemolytic anemia, G6PD carriers have to avoid a large number of drugs and foods. List of such "triggers" can be obtained from medical providers.

Anisocytosis is identified by RDW and is classified according to the size of RBC measured by MCV. According to this, it can be divided into

- Anisocytosis with microcytosis – Iron deficiency, sickle cell anemia

- Anisocytosis with macrocytosis – Folate or vitamin B deficiency, autoimmune hemolytic anemia, cytotoxic chemotherapy, chronic liver disease, myelodysplastic syndrome

Increased RDW is seen in iron deficiency anemia and decreased or normal in thalassemia major (Cooley's anemia), thalassemia intermedia

- Anisocytosis with normal RBC size – Early iron, vit B12 or folate deficiency, dimorphic anemia, Sickle cell disease, chronic liver disease, Myelodysplastic syndrome

Aplastic anemia is a rare disease in which the bone marrow and the hematopoietic stem cells that reside there are damaged. This causes a deficiency of all three blood cell types (pancytopenia): red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia). "Aplastic" refers to inability of the stem cells to generate mature blood cells.

It is most prevalent in people in their teens and twenties, but is also common among the elderly. It can be caused by heredity, immune disease, or exposure to chemicals, drugs, or radiation. However, in about half the cases, the cause is unknown.

The definitive diagnosis is by bone marrow biopsy; normal bone marrow has 30–70% blood stem cells, but in aplastic anemia, these cells are mostly gone and replaced by fat.

First line treatment for aplastic anemia consists of immunosuppressive drugs, typically either anti-lymphocyte globulin or anti-thymocyte globulin, combined with corticosteroids and ciclosporin. Hematopoietic stem cell transplantation is also used, especially for patients under 30 years of age with a related matched marrow donor.

Vitamin B deficiency can lead to anemia and neurologic dysfunction. A mild deficiency may not cause any discernible symptoms, but as the deficiency becomes more significant, symptoms of anemia may result, such as weakness, fatigue, light-headedness, rapid heartbeat, rapid breathing and pale color to the skin. It may also cause easy bruising or bleeding, including bleeding gums. GI side effects including sore tongue, stomach upset, weight loss, and diarrhea or constipation. If the deficiency is not corrected, nerve cell damage can result. If this happens, vitamin B deficiency may result in tingling or numbness to the fingers and toes, difficulty walking, mood changes, depression, memory loss, disorientation and, in severe cases, dementia.

The main syndrome of vitamin B deficiency is pernicious anemia. It is characterized by a triad of symptoms:

1. Anemia with bone marrow promegaloblastosis (megaloblastic anemia). This is due to the inhibition of DNA synthesis (specifically purines and thymidine)

2. Gastrointestinal symptoms: alteration in bowel motility, such as mild diarrhea or constipation, and loss of bladder or bowel control. These are thought to be due to defective DNA synthesis inhibiting replication in a site with a high turnover of cells. This may also be due to the autoimmune attack on the parietal cells of the stomach in pernicious anemia. There is an association with GAVE syndrome (commonly called watermelon stomach) and pernicious anemia.

3. Neurological symptoms: Sensory or motor deficiencies (absent reflexes, diminished vibration or soft touch sensation), subacute combined degeneration of spinal cord, seizures, or even symptoms of dementia and or other psychiatric symptoms may be present. Deficiency symptoms in children include developmental delay, regression, irritability, involuntary movements and hypotonia.

The presence of peripheral sensory-motor symptoms or subacute combined degeneration of spinal cord strongly suggests the presence of a B deficiency instead of folate deficiency. Methylmalonic acid, if not properly handled by B, remains in the myelin sheath, causing fragility. Dementia and depression have been associated with this deficiency as well, possibly from the under-production of methionine because of the inability to convert homocysteine into this product. Methionine is a necessary cofactor in the production of several neurotransmitters.

Each of those symptoms can occur either alone or along with others. The neurological complex, defined as "myelosis funicularis", consists of the following symptoms:

1. Impaired perception of deep touch, pressure and vibration, loss of sense of touch, very annoying and persistent paresthesias

2. Ataxia of dorsal chord type

3. Decrease or loss of deep muscle-tendon reflexes

4. Pathological reflexes — Babinski, Rossolimo and others, also severe paresis

Vitamin B deficiency can cause severe and irreversible damage, especially to the brain and nervous system. These symptoms of neuronal damage may not reverse after correction of hematological abnormalities, and the chance of complete reversal decreases with the length of time the neurological symptoms have been present.

Tinnitus may be associated with vitamin B deficiency.

Loss of appetite and weight loss can occur. Additional signs are weakness, sore tongue, headaches, heart palpitations, irritability, and behavioral disorders. In adults, anemia (macrocytic, megaloblastic anemia) can be a sign of advanced folate deficiency.

Women with folate deficiency who become pregnant are more likely to give birth to low birth weight premature infants, and infants with neural tube defects. In infants and children, folate deficiency can lead to failure to thrive or slow growth rate, diarrhea, oral ulcers, megaloblastic anemia, neurological deterioration. Microcephaly, irritability, developmental delay, seizures, blindness and cerebellar ataxia can also be observed.

Vitamin B deficiency can also cause symptoms of mania and psychosis, fatigue, memory impairment, irritability, depression, ataxia, and personality changes. In infants symptoms include irritability, failure to thrive, apathy, anorexia, and developmental regression.

CDA type IV is characterized by mild to moderate splenomegaly. Hemoglobin is very low and patients are transfusion dependent. MCV is normal or mildly elevated. Erythropoiesis is normoblastic or mildly to moderately megaloblastic. Nonspecific erythroblast dysplasia is present.

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).