This is an inherited condition characterized by the body’s inability to breakdown certain proteins and fats which can result in the harmful quantity of organic acids and toxins. The symptoms of this disorder can develop in early infancy and can be mild or life-threatening. Some of the complications of this condition include chronic kidney disease, pancreatitis and intellectual disability. If treatment is not initiated, it can cause coma and death in some cases. This is one of the various conditions that are called the inborn error of metabolism. Methylmalonic acidemia is estimated to affect around 1 in every 50,000 to 100,000 infants in the United States.
Causes
The genetic mutations identified to cause this condition are the genes MUT, MMAA, MMAB, MMADHC and MCEE. The long-term problem of this disease is based on the gene affected and the severity of the mutation. Around 60% of the affected cases develop as the result of a mutation in the gene MUT that produces an enzyme called methylmalonyl CoA mutase which breaks down the amino acids, lipids and cholesterol. The genetic mutation prevents these molecules to be effectively broken down which can accumulate in various organs and tissues of the body. Other cases can develop when the mutation occur in the MMAA, MMAB or MMADHC gene. The proteins produced by these genes can affect the normal activity of methylmalonyl CoA mutase causing the associated symptoms. The mutation in the gene MCEE causes the disrupted function of the methylmalonyl CoA epimerase produced by this gene. The genetic mutation in the MCEE gene causes the mild form of this disease. Most of the genetic mutation is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell are defective.
Symptoms
The symptoms can develop when the child begins to consume more protein. Some of the symptoms include dehydration, seizures, lethargy, frequent yeast infections, vomiting, developmental delays, brain diseases that deteriorate (progressive encephalopathy) and failure to thrive.
Diagnosis
This condition can be diagnosed prenatally by measuring the activity of the responsible enzyme in the fluid or the tissue sample taken from the uterus. In most of the cases, this condition can be diagnosed in the first few weeks of the infant’s life based on the clinical evaluation, family history and various tests. The cultured skin cells can detect the deficiency of the responsible enzyme. Other laboratory studies can detect the high level of acids and the accumulations of ketone bodies in tissues. Also, the urine and blood samples can indicate high levels of glycine, increased level of ammonia in the blood and decreased level of white blood cells.
Treatment
The treatment consists of a carefully monitored diet of the affected children which can include the low protein diet and to prevent amino acids isoleucine, valine, threonine and methionine. High doses of vitamin B12 and administration of hydroxocobalamin can help restore the normal metabolism.
References
https://rarediseases.org/rare-diseases/acidemia-methylmalonic/
https://ghr.nlm.nih.gov/condition/methylmalonic-acidemia#inheritance
https://medlineplus.gov/ency/article/001162.htm
