Published on June 15, 2015, research performed on the effects of methylmalonic acid on neurons isolated from fetal rats in an in vitro setting using a control group of neurons treated with an alternate acid of similar pH. These tests have suggested that methylmalonic acid causes decreases in cellular size and increase in the rate of cellular apoptosis in a concentration dependent manner with more extreme effects being seen at higher concentrations. Furthermore, micro-array analysis of these treated neurons have also suggested that on an epigenetic-level methylmalonic acid alters the transcription rate of 564 genes, notably including those involved in the apoptosis, p53, and MAPK signaling pathways. Mitochondrial dysfunction
As the conversion of methylmalonyl-CoA to succinyl-CoA takes place inside the mitochondria, mitochondrial dysfunction as a result of diminished electron transport chain function has long been suspected as a feature in MMA. Recent research has found that in rat models mitochondria of rats affected by the disorder grow to unusual size, dubbed megamitochondria. These megamitochondria also appear to have deformed internal structures and a loss in electron richness in their internal matrix. These megamitochondria also showed signs of decreased respiratory chain function, particularly in respiratory complex IV which only functioned at about 50% efficiency. Similar changes were identified in the mitochondria of a liver sample removed during transplant from a 5-year-old boy suffering from MMA. Benign mut phenotype
Recent case studies in several patients presenting nonresponsive mut0 MMA with a specific mutation designated p.P86L have suggest the possibility of further subdivision in mut type MMA might exist.
Lymphocytosis is an increase in the number or proportion of lymphocytes in the blood. Absolute lymphocytosis is the condition where there is an increase in the lymphocyte count beyond the normal range while relative lymphocytosis refers to the condition where the proportion of lymphocytes relative to white blood cell count is above the normal range. In adults, absolute lymphocytosis is present when the lymphocyte count is greater than 5000 per microliter (5.0 x 109/L), in older children greater than 7000 per microliter and in infants greater than 9000 per microliter. Lymphocytes normally represent 20% to 40% of circulating white blood cells. When the percentage of lymphocytes exceeds 40%, it is recognized as relative lymphocytosis. Causes
Lymphocytosis is a feature of infection, particularly in children. In the elderly, lymphoproliferative disorders, including chronic lymphocytic leukemia and lymphomas, often present with lymphadenopathy and a lymphocytosis.Causes of absolute lymphocytosis include:

acute viral infections, such as infectious mononucleosis (glandular fever), hepatitis and Cytomegalovirus infection
other acute infections such as pertussis
some protozoal infections, such as toxoplasmosis and American trypanosomiasis (Chagas disease)
chronic intracellular bacterial infections such as tuberculosis or brucellosis
chronic lymphocytic leukemia
acute lymphoblastic leukemia
lymphoma
post-splenectomy state
CARD11-related congenital B cell lymphocytosis (rare, also known as BENTA disease)Causes of relative lymphocytosis include:

age less than 2 years;
acute viral infections;
connective tissue diseases,
thyrotoxicosis,
Addisons disease,
splenomegaly with splenic sequestration of granulocytes. Diagnosis
Lymphocytosis is usually detected when a complete blood count is obtained. If not provided the lymphocyte count can be calculated by multiplying the total white blood cell (WBC) count by the percentage of lymphocytes found in the differential count.