Metabolic studies in older mentally retarded patients: Significance of metabolic testing and correlation with the clinical phenotype

In 471 adult mentally retarded adult patients (mean age 46 years; 92.6% mal es) living in an institution for the mentally retarded, a clinical examinat ion, cytogenetic and molecular studies were done. 306 patients were screene d for metabolic disorders. In 7 additional patients a metabolic disorder (p henylketonuria (n=5), mucopolysaccharidosis type III (Sanfilippo syndrome, type A) (n=1) and mucopolgsaccharidosis type VII (Sly syndrome) (n=1)) was diagnosed in the past. The abnormal metabolic findings in this group of 313 patients were classified in three categories and the clinical findings are reported: 1, metabolic disorders as the cause of mental retardation (MR), 2. metabolic disorders not explaining the MR, and 3, metabolic abnormalitie s of unknown significance. The first two groups included 16 patients, i.e. 26.2% of the group of monogenic disorders and 3.4% of the total population: phenylketonuria (PKU) (n=5), S-sulfocysteinuria (n=3), mucopolysaccharidos is type III (Sanfilippo syndrome, type A) (n=1) and Gm1-gangliosidosis type 3 (n=1) (first group), and mucopolysaccharidosis type VII (Sly syndrome) ( n=1), Niemann-Pick syndrome, type B (n=1), cystinuria (n=1) and hyperprolin emia type 1 (n=3) (second group). The third group included patients with ci trullinemia (n=2), methionine sulphoxide reductase deficiency (n=1), ornith inemia (n=1), glycinuria (n=20), neuraminaciduria (n=8), uraciluria (n=6) a nd diabetes mellitus (n=2), Screening for Congenital Disorders of Glycosyla tion (CDG) in 144 patients and for Smith-Lemli-Opitz syndrome (SLO) in a se lected group of 6 patients was normal. Of the total group of 306 patients s creened for inborn errors of metabolism, only 5 (1.6%) were found with a tr ue metabolic disorder. These 5 patients presented clinical symptoms, neurod egenerative or behavioural problems, indicating further metabolic screening . The present study illustrates that a selected group of patients with ment al retardation of unknown origin are candidates for metabolic screening, es pecially if aberrant behaviour, neurodegenerative problems or dysmorphic fe atures are present.