HMG-CoA Lyase deficiency is a disorder caused by a deficiency of the enzyme HMG-CoA Lyase, which is responsible for helping to break down protein. People with this disorder develop symptoms during the first year of their life. These signs include vomiting, diarrhea, dehydration, being tired, and muscle weakness. Certain triggers such as illness, fasting, or eating large amounts of protein can cause episodes of worsening symptoms. During these episodes, people with this disorder develop additional complications, including very low blood sugar, eating and breathing problems, diarrhea, and coma. If left untreated, these episodes can cause brain damage, resulting in intellectual disability. These episodes could also be fatal without treatment. Between episodes, affected children appear normal, though the possibility of developing an enlarged heart or pancreas and vision and hearing loss increases with each episode. If treatment with a strictly managed diet and avoidance of protein and fasting is initiated before symptoms appear, it is possible for affected children to live healthy lives with normal growth and development. However, neurologic damage is still possible during episodes of stress from illness. HMG-CoA Lyase deficiency is caused by pathogenic variants in the HMGCL gene.