Complex Phenotypes in Inborn Errors of Metabolism: Overlapping Presentations in Congenital Disorders of Glycosylation and Mitochondrial Disorders

Abstract

Congenital disorders of glycosylation (CDG) and mitochondrial disorders have overlapping clinical features, including central nervous system, cardiac, gastrointestinal, hepatic, muscular, endocrine, and psychiatric disease. Specific abnormalities orienting the clinician toward the right diagnostic approach include abnormal fat distribution, coagulation abnormalities, together with anticoagulation abnormalities, hyperinsulinism, and congenital malformations in CDG. Diabetes, sensorineural deafness, and depression are very rare in CDG but common in mitochondrial disease. Chronic lactic acidosis is highly suggestive of mitochondrial dysfunction. Serum transferrin isoform analysis is specific for glycosylation abnormalities but not abnormal in all types of CDG.

Keywords: Cholestasis; Cutis laxa; Glycosylation; Hypoglycemia; Lactic acid; Mitochondrial disease; Stroke-like episodes; Transferrin isoelectric focusing (TIEF).