Increased serum α-ketoglutarate and serum glutamate levels were observed in ten patients presenting the characteristic features of the de Lange syndrome. Both anomalies may prove beneficial in diagnosis of the syndrome. Serum glutaminase, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and glutamic dehydrogenase activities were within the normal ranges. Hypoaminoacidura and hypogammaglobulinemia were present in six of the patients. Immunological studies indicated that these patients had normal IgA, IgG, and IgM levels. Family studies revealed elevated or high-normal glutamate levels in the parents and certain siblings of the patients, indicating that the hyperglutamicacidemia may be inherited. All de Lange cases appeared to be sporadic, although a second cousin of one of the patients may have had the syndrome. Synophrys and clinodactyly were observed in relatives of one of the patients. The de Lange syndrome may be the result of an inherited metabolic error, although the exact nature of the enzymatic defect is uncertain.
Daniel WL, Higgins JV. Biochemical and Genetic Investigation of the de Lange Syndrome. Am J Dis Child. 1971;121(5):401-405. doi:10.1001/archpedi.1971.02100160071007