Continuing education in neurometabolic disorders--serine deficiency disorders

Serine deficiency disorders comprise a new group of inborn errors of serine metabolism. Patients affected with these disorders present with major neurological symptoms including congenital microcephaly, seizures, psychomotor retardation or polyneuropathy. The diagnosis of serine deficiency is based on the detection of low concentrations of the amino acids serine and glycine in fasted plasma and cerebrospinal fluid (CSF). Amino acid analysis of cerebrospinal fluid is preferable over plasma analysis, because the deficiencies are more pronounced in CSF. Because of the interference of amino acids absorbed from the diet, diagnostic procedures have to be performed in the fasted state. Although the disorders are probably rare and not many cases have been reported, recognition of serine deficiency is important, given the fact that the disorders are potentially treatable. The clinical symptoms respond well to amino acid replacement therapy. So far, three serine deficiency disorders have been reported; 3-phosphoglycerate dehydrogenase deficiency, 3-phosphoserine phosphatase deficiency and a still unexplained serine deficiency disorder. In this paper, we will discuss the various serine deficiency disorders, their biochemical abnormalities and the results of amino acid replacement therapy.