There is evidence to suggest that the central nervous system may metabolize methylmalonyl-CoA in a system isolated from the rest of the body. If this is the case, transplantation may not reverse the neurological effects of methylmalonic acid previous to the transplant or prevent further damage to the brain by continued build up. Prognosis
The prognosis will vary depending on the severity of the condition and the individuals response to treatment. Prognosis is typically better for those with cobalamin-responsive variants and not promising in those suffering from noncobalamin-responsive variants. Milder variants have a higher frequency of appearance in the population than the more severe ones. Even with dietary modification and continued medical care, it may not be possible to prevent neurological damage in those with a nonresponsive acidemia. Without proper treatment or diagnosis, it is not uncommon for the first acidemic attack to be fatal.Despite these challenges, since it was first identified in 1967, treatment and understanding of the condition has improved to the point where it is not unheard of for even those with unresponsive forms of methylmalonic acidemia to be able to reach adulthood and even carry and deliver children safely. Research
Nosologic history
MMA was first characterized by Oberholzer et al. in 1967. Neurologic effects
That MMA can have disastrous effects on the nervous system has been long reported; however, the mechanism by which this occurs has never been determined.
Diagnosis
One of, if not the most common form of organic acidemia, methylmalonic acidemia is not apparent at birth as symptoms usually do not present themselves until proteins are added to the infants diet. Because of this, symptoms typically manifest anytime within the first year of life. Due to the severity and rapidity in which this disorder can cause complications when left undiagnosed, screening for methylmalonic acidemia is often included in the newborn screening exam.Because of the inability to properly break down amino acids completely, the byproduct of protein digestion, the compound methylmalonic acid, is found in a disproportionate concentration in the blood and urine of those afflicted. These abnormal levels are used as the main diagnostic criteria for diagnosing the disorder. This disorder is typically determined through the use of a urine analysis or blood panel. The presence of methylmalonic acidemia can also be suspected through the use of a CT or MRI scan or ammonia test, however these tests are by no means specific and require clinical and metabolic/correlation. Elevated levels of ammonia, glycine, and ketone bodies may also be present in the blood and urine. Types
Methylmalonic acidemia has varying diagnoses, treatment requirements and prognoses, which are determined by the specific genetic mutation causing the inherited form of the disorder.