Methylmalonic acidemia, also called methylmalonic aciduria, is an autosomal recessive metabolic disorder that disrupts normal amino acid metabolism. It is a classical type of organic acidemia. The result of this condition is the inability to properly digest specific fats and proteins, which in turn leads to a buildup of a toxic level of methylmalonic acid in the blood.Methylmalonic acidemia stems from several genotypes, all forms of the disorder usually diagnosed in the early neonatal period, presenting progressive encephalopathy, and secondary hyperammonemia. The disorder can result in death if undiagnosed or left untreated. It is estimated that this disorder has a frequency of 1 in 48,000 births, though the high mortality rate in diagnosed cases make exact determination difficult. Methylmalonic acidemias are found with an equal frequency across ethnic boundaries. Symptoms and signs
Depending on the affected gene(s), this disorder may present symptoms that range from mild to life-threatening. Stroke
Progressive encephalopathy
Seizure
Kidney failure
Vomiting
Dehydration
Failure to thrive and developmental delays
Lethargy
Repeated yeast infections
Acidosis
Hepatomegaly
Hypotonia
Pancreatitis
Respiratory distress

Cause
Genetic
The inherited forms of methylmalonic acidemia cause defects in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase.Vitamin B12 is also needed for the conversion of methylmalonyl-CoA to succinyl-CoA. Mutations leading to defects in vitamin B12 metabolism or in its transport frequently result in the development of methylmalonic acidemia.This disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene—one from each parent—must be inherited to be affected by the disorder.
Potassium-aggravated myotonia is a rare genetic disorder that affects skeletal muscle. Beginning in childhood or adolescence, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Myotonia causes muscle stiffness, often painful, that worsens after exercise and may be aggravated by eating potassium-rich foods such as bananas and potatoes. Stiffness occurs in skeletal muscles throughout the body. Potassium-aggravated myotonia ranges in severity from mild episodes of muscle stiffness to severe, disabling disease with frequent attacks. Potassium-aggravated myotonia may, in some cases, also cause paradoxical myotonia, in which myotonia becomes more severe at the time of movement instead of after movement has ceased. Unlike some other forms of myotonia, potassium-aggravated myotonia is not associated with episodes of muscle weakness.Mutations in the SCN4A gene cause potassium-aggravated myotonia. The SCN4A gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. For the body to move normally, skeletal muscles contract and relax in a coordinated way. Muscle contractions are triggered by the flow of positively charged ions, including sodium, into skeletal muscle cells. The SCN4A protein forms channels that control the flow of sodium ions into these cells. Mutations in the SCN4A gene alter the usual structure and function of sodium channels. The altered channels cannot properly regulate ion flow, increasing the movement of sodium ions into skeletal muscle cells.