N-Acetylcysteine Therapy in an Infant with Transaldolase Deficiency Is Well Tolerated and Associated with Normalization of Alpha Fetoprotein Levels

Abstract

Transaldolase deficiency is a rare autosomal recessive disorder of the pentose phosphate pathway that presents clinically with infantile-onset hepatopathy progressing to cirrhosis, nephropathy, connective tissue abnormalities resembling cutis laxa, coagulopathy, cytopenias, and increased risk of hepatocellular carcinoma. In many cases, death occurs in infancy or early childhood. There is no established treatment for transaldolase deficiency in humans. Recent work in a knockout mouse model of transaldolase deficiency has demonstrated a benefit to supplementation with the glutathione precursor N-acetylcysteine (NAC). We describe an infant with genetically confirmed transaldolase deficiency with multisystem involvement, including liver enlargement and markedly elevated alpha fetoprotein. Acetaminophen was strictly avoided. Treatment with oral NAC over a 6-month period was well tolerated and was associated with a sustained normalization of alpha fetoprotein levels and stable clinical course. The clinical significance of normalized serum alpha fetoprotein in this patient is not certain, although it may reflect decreased hepatocyte injury and reduced hepatocarcinogenesis as has been suggested in the mouse disease model. NAC supplementation may provide benefit in humans with transaldolase deficiency. Longer follow-up and data on the response of additional patients with transaldolase deficiency to NAC supplementation will be required to further evaluate efficacy and optimize dosing.

Competing interests: None declared

Appendices

Synopsis

N-acetylcysteine therapy in an infant with transaldolase deficiency was well tolerated and associated with normalization of serum alpha fetoprotein levels. NAC may provide benefit in humans with transaldolase deficiency, but additional cases and longer follow-up are required.

Author Contributions

Lance H. Rodan: Preparation of manuscript

Gerard T. Berry: Critical revision of manuscript, supervisor

Guarantor

Lance H. Rodan

Competing Interest Statement

Lance H. Rodan and Gerard T. Berry have nothing to declare.

Funding

There are no sponsors or funding to declare.

Compliance with Ethics Guidelines

Not required

Patient Consent Statement

Not applicable since the report does not contain any identifying patient information.

Conflict of Interest

There is no conflict of interest.