It has been suggested that disturbed methylation via SAM could be responsible for the relation between folate and NTDs. This may also apply to choline. Certain mutations that disturb choline metabolism increase the prevalence of NTDs in newborns, but the role of dietary choline deficiency remains unclear, as of 2015. Cardiovascular diseases and cancer
Choline deficiency can cause fatty liver, which increases cancer and cardiovascular disease risk. Choline deficiency also decreases SAM production, which partakes in DNA methylation – this decrease may also contribute to carcinogenesis. Thus, deficiency and its association with such diseases has been studied. However, observational studies of free populations have not convincingly shown an association between low choline intake and cardiovascular diseases or most cancers. Studies on prostate cancer have been contradictory. Cognition
Studies observing the effect between higher choline intake and cognition have been conducted in human adults, with contradictory results. Similar studies on human infants and children have been contradictory and also limited. Perinatal development
Both pregnancy and lactation increase demand for choline dramatically. This demand may be met by upregulation of PEMT via increasing estrogen levels to produce more choline de novo, but even with increased PEMT activity, the demand for choline is still so high that bodily stores are generally depleted.
Cold autoimmune hemolytic anemia caused by cold-reacting antibodies. Autoantibodies that bind to the erythrocyte membrane leading to premature erythrocyte destruction (hemolysis) characterize autoimmune hemolytic anemia. Presentation
A common complaint among patients with cold agglutinin disease is painful fingers and toes with purplish discoloration associated with cold exposure. In chronic cold agglutinin disease, the patient is more symptomatic during the colder months. Cold agglutinin mediated acrocyanosis differs from Raynaud phenomenon. In Raynaud phenomena, caused by vasospasm, a triphasic color change occurs, from white to blue to red, based on vasculature response. No evidence of such a response exists in cold agglutinin disease. Other symptoms

Respiratory symptoms: May be present in patients with M pneumoniae infection. Hemoglobinuria (the passage of dark urine that contains hemoglobin), A rare symptom that results from hemolysis, this may be reported following prolonged exposure to cold, hemoglobinuria is more commonly seen in paroxysmal cold hemoglobinuria. Chronic fatigue, Due to anemia. Causes
Cold agglutinins develop in more than 60% of patients with infectious mononucleosis, but hemolytic anemia is rare. Classic chronic cold agglutinin disease is idiopathic, associated with symptoms and signs in relation to cold exposure. Causes of the monoclonal secondary disease include the following:

B-cell neoplasms - Waldenström macroglobulinemia, lymphoma, chronic lymphoid leukemia, myeloma
Non hematologic neoplasmsCauses of polyclonal secondary cold agglutinin disease include the following:

Mycoplasma infections. Viral infections: Infectious mononucleosis due to Epstein-Barr virus (EBV) or CMV, Mumps, varicella, rubella, adenovirus, HIV, influenza, hepatitis C.
Bacterial infections: Legionnaire disease, syphilis, listeriosis and Escherichia coli. Parasitic infections: Malaria and trypanosomiasis.