Gaucher Disease

Gaucher disease (pronounced as GO-SHEY) is an autosomal recessive inborn error of metabolism caused by mutations in the glucocerebrosidase (GBA1) gene. GBA1 is an enzyme that cleaves the beta-glucosidic linkage of glucocerebroside lipids.

Gaucher disease is a poignant testament to the intricate interplay between genetics, biochemistry, and clinical medicine. Named after the French physician Philippe Charles Ernest Gaucher, who first described it in 1882, this inherited metabolic disorder is characterized by the accumulation of lipids, specifically glucocerebroside, within various tissues and organs throughout the body. Gaucher disease can manifest in a spectrum of clinical presentations, with mild to severe symptoms affecting individuals of diverse ages and backgrounds.

Inborn errors of metabolism are particularly relevant in pediatrics since their presentation is very often (but not always) in the neonatal period of infancy. There are 5 known types of Gaucher disease: type 1, type 2, type 3, perinatal lethal, and cardiovascular. The perinatal lethal form is the most severe, and its complications can begin before birth or in early infancy.

Knowing the major manifestations of any inborn error of metabolism is the key to making a diagnosis. Inborn errors of metabolism primarily result from the lack (or insufficient levels) of specific enzymes needed: (1) to convert fat or carbohydrates to energy or (2) to break down amino acids or other metabolites, allowing them to accumulate and become toxic if not treated. Gaucher disease is a “toxic accumulation” inborn error of metabolism due to the accumulation of glucocerebroside lipids. Toxic accumulation inborn errors of metabolism fall into 3 major categories: localized toxicity, circulating toxicity, or a combination of both. Gaucher disease is an example of localized toxicity.