Sign Up for a Free Account
  • Updated 10.21.2020
  • Released 08.04.2003
  • Expires For CME 10.21.2023

Glutathione synthetase deficiency

Introduction

Overview

Manifestations of glutathione synthetase deficiency usually include hemolytic anemia, often include metabolic acidosis, and sometimes include progressive neurologic symptoms as well as other systemic signs. At least a third of the most severely affected patients die of acidosis in the neonatal period. Among surviving patients, the most severely affected patients have intellectual disability, progressive cerebellar disease and ataxia, recurrent bacterial infections, as well as chronic metabolic acidosis and hemolytic anemia. Although there is no specific curative therapy, beneficial treatments include correction of acidosis, blood transfusion, and supplementation with antioxidants. Glutathione replacement is extremely difficult to achieve in practice.

Key points

• Manifestations of glutathione synthetase deficiency usually include hemolytic anemia, often include metabolic acidosis, and sometimes include progressive neurologic symptoms as well as other systemic signs (eg, respiratory distress, sepsis, hyperbilirubinemia).

• Although mildly affected patients manifest only a mild to moderate hemolytic anemia, at least a third of the most severely affected patients die of acidosis in the neonatal period.

• Among surviving patients, the most severely affected patients have intellectual disability (IQs often from 50 to 60), progressive cerebellar disease and ataxia, recurrent bacterial infections, as well as chronic metabolic acidosis and hemolytic anemia.

• Although there is no specific curative therapy for this disease, beneficial treatments include correction of acidosis, blood transfusion, and supplementation with antioxidants.

• Glutathione replacement is extremely difficult to achieve in practice.

Historical note and terminology

Glutathione synthethase deficiency is an autosomal recessive disorder that was first diagnosed in 1970 in a teenager with slowly progressive neurologic disorder and markedly elevated excretion of 5-oxoproline in the urine as well as a history of unexplained jaundice at birth and a history of chronic metabolic acidosis. Subsequently, newborns with hemolytic anemia and organic acidosis were recognized as having similar elevations in this urinary metabolite. The identification of reduced cellular glutathione levels and deficient glutathione synthetase activity established this disorder as a unique entity.

This is an article preview.
Start a Free Account
to access the full version.

  • Nearly 3,000 illustrations, 
including video clips of 
neurologic disorders.

  • Every article is reviewed by our esteemed Editorial Board for accuracy and currency.

  • Full spectrum of 
neurology in 1,200 
comprehensive articles.

Questions or Comment?

MedLink, LLC

10393 San Diego Mission Rd, Suite 120

San Diego, CA 92108-2134

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com