What is 3-methylcrotonyl-CoA Carboxylase Deficiency, MCCC2-related? 3-methylcrotonyl-CoA carboxylase deficiency, or 3-MCCD, is an inherited condition caused by an inability to break down the amino acid leucine. Amino acids are essential for proper growth and development. Two genes cause the condition. 3-methylcrotonyl-CoA carboxylase deficiency, MCCC2-related, is caused by harmful genetic changes (variants) in the MCCC2 gene. Symptoms for individuals affected with 3-MCCD are highly variable. The first symptom is usually an episode known as a “metabolic crisis.” During these episodes, individuals have low blood sugar, vomiting, lack of energy, difficulty feeding, irritability, and weak muscles (hypotonia). These episodes can be triggered by infections, not eating for long stretches (fasting), or a protein-rich diet. In some cases, the episodes may cause neurological abnormalities such as metabolic stroke, weakness or inability to move on one side of the body (hemiparesis), and decreased blood flow or oxygen to the brain (encephalopathy). Some individuals may experience developmental delays. Symptoms can appear as early as infancy or early childhood, but many individuals do not develop symptoms until adulthood or may live their entire lives without any apparent symptoms. How common is 3-methylcrotonyl-CoA Carboxylase Deficiency, MCCC2-related? 3-methylcrotonyl-CoA carboxylase deficiency has an incidence of approximately 1 in 36,000 births. How is 3-methylcrotonyl-CoA carboxylase deficiency treated? There is no cure for 3-methylcrotonyl-CoA carboxylase deficiency. Treatment for the condition is directed at managing an individual's specific symptoms. Many asymptomatic individuals will never require any treatment. Common treatments include a low-leucine diet with limited protein and/or oral L-carnitine supplementation. Individuals are advised to avoid fasting, particularly for infants and young children. A leucine-free medical formula may be recommended for some infants to help prevent metabolic crises. During times of significant illness, an emergency regimen of IV glucose may be used. What is the prognosis for an individual with 3-methylcrotonyl-CoA carboxylase deficiency? The prognosis depends on the severity of the symptoms but is generally good. For the most severely affected, without treatment for metabolic crises, the condition can lead to developmental delay, seizures, coma, or even death. Treatment is often unnecessary for those who are asymptomatic, and the prognosis may be no different than somebody who does not have the condition. Other names for3-methylcrotonyl-CoA carboxylase deficiency, MCCC2-related 3-MCC deficiency 3-Methylcrotonylglycinuria 3-Methylcrotonylglycinuria II 3-methylcrotonyl-CoA carboxylase deficiency MCC2 Deficiency (MCC2D) MCCB Methylcrotonylglycinuria Type II References Arnold et al., 2008, Mol Genet Metab., 93(4):363-70, PMID: 18155630 Gregg et al., 2021, Genet Med., 23(10):1793-1806, PMID: 34285390 Grünert et al., 2012, Orphanet J Rare Dis., 7(31), PMID: 22642865 OMIM: Online Mendelian Inheritance in Man, OMIM [210210], 2023, https://www.omim.org/entry/210210