Mental retardation caused by errors of metabolism

Inborn errors of metabolism (IEM) are rare causes of mental retardation (MR) and constitute about 1% of all cases of MR in the Caucasian population. In contrast to recommendations for other diagnostic laboratory tests in MR, e.g. chromosome analysis, there is no consensus on criteria for metabolic testing. IEM, however, are potentially treatable and their timely diagnosis is of relevance for prognosis, recurrence risk and the possibility of prenatal diagnosis. On the basis of current evidence, the following important IEM leading to nonspecific MR or to conditions with MR as the predominant clinical presentation are highlighted: creatine deficiency syndromes (in particular creatine transporter deficiency), mucopolysaccharidoses III (in particular IIIB), beta-mannosidosis, specific organic acidurias, homocystinuria, CDG (congenital disorder of glycosylation), and specific disorders of purine and pyrimidine metabolism. In addition, urea cycle disorders, sterol synthesis defects and additional aminoacidurias are briefly considered. A rationale for metabolic testing in unexplained MR is presented.