DLD-deficiency is characterized by diverse clinical manifestations. The disorder usually presents itself in infancy in the form of recurrent episodes of generalized hypotonia, vomiting, lethargy, abdominal pain, lactate acidosis, hypoglycaemia, and/or hyperammonemia. These symptoms are the consequence of potentially fatal acute metabolic decompensation. Such metabolic episodes are often triggered by fever, viral infection, fasting, etc.. If infants survive, most frequently severe neurological symptoms (ataxia, seizures, developmental delay, microcephaly, Leigh syndrome) or cardiomyopathy develop. Late-onset isolated hepatic manifestations have also been described and associated mostly with one specific LADH-variant (Gly194Cys). Two adult patients have recently been reported with myopathic phenotypes and overall mild presentations.
DLD