A Patient with Nonketotic Hyperglycinemia: Biochemical Findings and Therapeutic Approaches

Abstract

Extract: High voltage paper electrophoresis of urine and quantitative amino acid analysis of serum revealed a greatly increased excretion of glycine as well as hyperglycinemia in a patient on the 7th day of life. The cerebrospinal fluid of the infant showed a marked increase in isoleucine concentration as well as elevation of the glycine level. After establishment of the enzymic defect in a liver biopsy with the aid of (1-¹⁴C) glycine and (2-¹⁴C) glycine, several therapeutic approaches have been performed which were based, among other things, on replenishment of the C₁ units pool. Administration of compounds such as leucovorin (N⁵-formyl tetrahydrofolate (THF)), methionine, choline, and formate did not result in a normalization of the serum glycine level. During treatment with methionine (350 mg/kg/24 hr) a strong hypermethioninemia (1,240 μmol/liter) and sarcosinemia (5,180 μmol/liter) developed. A supply of pyridoxine, a precursor of pyridoxal phosphate, the latter being a cofactor in the glycine cleavage system, did not influence the serum glycine level. It was concluded that our patient did not show a deficiency of N⁵, N¹⁰-methylene-THF as a result of a defective glycine cleavage system.

Speculation: In spite of comprehensive investigations which concerns patients who suffer from nonketotic hyperglycinemia, additional studies are required to enhance our knowledge of the biochemical disturbance in these patients. This will provide new therapeutic approaches which are urgently desired, as no efficacious measures are available now.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD