title: Metabolic studies in older mentally retarded patients: significance of metabolic testing and correlation with the clinical phenotype.
abstract: In 471 adult mentally retarded adult patients (mean age 46 years; 92.6% males) living in an institution for the mentally retarded, a clinical examination, cytogenetic and molecular studies were done. 306 patients were screened for metabolic disorders. In 7 additional patients a metabolic disorder (phenylketonuria (n = 5), mucopolysaccharidosis type III (Sanfilippo syndrome, type A) (n = 1) and mucopolysaccharidosis 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 abnormalities 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), mucopolysaccharidosis 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 hyperprolinemia type 1 (n = 3) (second group). The third group included patients with citrullinemia (n = 2), methionine sulphoxide reductase deficiency (n = 1), ornithinemia (n = 1), glycinuria (n = 20), neuraminaciduria (n = 8), uraciluria (n = 6) and diabetes mellitus (n = 2). Screening for Congenital Disorders of Glycosylation (CDG) in 144 patients and for Smith-Lemli-Opitz syndrome (SLO) in a selected group of 6 patients was normal. Of the total group of 306 patients screened for inborn errors of metabolism, only 5 (1.6%) were found with a true metabolic disorder. These 5 patients presented clinical symptoms, neurodegenerative or behavioural problems, indicating further metabolic screening. The present study illustrates that a selected group of patients with mental retardation of unknown origin are candidates for metabolic screening, especially if aberrant behaviour, neurodegenerative problems or dysmorphic features are present.
authors.affiliation: Center for Human Genetics, University of Leuven, Belgium.
authors.forename: G J
authors.initials: GJ
authors.lastname: Van Buggenhout
authors.forename: J M
authors.initials: JM
authors.lastname: Trijbels
authors.forename: R
authors.initials: R
authors.lastname: Wevers
authors.forename: J C
authors.initials: JC
authors.lastname: Trommelen
authors.forename: B C
authors.initials: BC
authors.lastname: Hamel
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: J P
authors.initials: JP
authors.lastname: Fryns
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000150:complications* / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D013577:Syndrome