Screening of inherited oligosaccharidurias among mentally retarded patients in northern Finland.

Urinary oligosaccharides were screened with thin-layer chromatography among 1058 mentally retarded patients of a geographically defined area with an approximate population of 200,000. Aspartylglucosaminuria was detected in 26 cases and Salla disease in 24 cases. All patients with aspartylglucosaminuria had the correct diagnosis before the screening, whereas two new cases of Salla disease were detected. No other inherited metabolic diseases were found. The results demonstrate the accuracy of the TLC method, and indicate a high gene frequency of those two lysosomal storage diseases in the population of northern Finland.

The incidence of Down syndrome in northern Finland with special reference to maternal age.

The incidence of live-born children with Down syndrome was found to be 1.73/1000 (1:578) in northern Finland over the years 1965 to 1979. Despite a marked reduction in the proportion of older mothers, no significant change in the incidence was observed. Instead, an age-specific rise in the incidence for mothers aged 25 to 29 years could be shown during the last five-year period in years 1975 to 1979.

Metabolism of collagen in aspartylglycosaminuria: urinary excretion of hydroxyproline.

Aspartylglycosaminuria (AGU) is a lysosomal storage disorder of glycoprotein degradation characterized by severe mental retardation and connective tissue alterations. We have previously described low collagen production in skin fibroblast cultures from AGU patients. In the present work we showed that the urinary excretion of hydroxyproline (total, non-dialysable and free hydroxyproline as indicators of collagen metabolism) was reduced in young AGU patients in comparison with age-matched controls. In adult patients no significant difference was detected. The results support the view that reduced collagen production is associated with the connective tissue abnormalities in this disorder.

Salla disease: a new lysosomal storage disorder with disturbed sialic acid metabolism.

Salla disease is a lysosomal storage disorder associated with increased urinary excretion of free sialic acid. The main clinical features in 34 patients were severe psychomotor retardation of early onset, ataxia, athetosis, rigidity, spasticity, and impaired speech. Growth retardation, thick calvarium, and exotropia were present in about half the patients. The amplitude of EEG decreased progressively with increasing age. Life span appears to be normal; the age range of the patients was 3 to 63 years. Genealogic studies suggest an autosomal mode of inheritance. A thin-layer method is described for the detection of increased urinary free sialic acid excretion. The basic defect is so far unknown.

Increased urinary excretion of free N-acetylneuraminic acid in thirteen patients with Salla disease.

Thirteen severely retarded patients with Salla disease, a new type of lysosomal storage disorder, have been studied biochemically. All patients excreted approximately ten times more free sialic acid than normal individuals. The isolated sialic acid was characterized by paper chromatography, thin-layer chromatography, optical rotation, 13C and 1H nuclear magnetic resonance spectroscopy, and mass spectrometry of its permethylated derivative. The results clearly indicated that the excreted sialic acid was identical to N-acetylneuraminic acid. The main sialylated trisaccharide present in the urine of the patients was identified as 3'-sialyllactose by sugar and methylation analysis. The excreted amounts were found to be within normal range.

"Salla disease": a new lysosomal storage disorder.

Severe mental retardation, coarse facial features, clumsiness, and speech failure were common findings in three brothers and one female third-cousin of a family from northern Finland. All the patients had vacuolated lymphocytes in peripheral blood smears, and electron microscopy of fresh skin biopsy specimens showed abundant cytoplasmic inclusions in various types of cells of the skin. Eight lysosomal hydrolases were assayed in peripheral blood lymphocytes and cultured skin fibroblasts, but no enzyme deficiency was detected. Urinary excretion of mucopolysaccharides, amino acids, glycoasparagines, and oligosaccharides was normal. Clinical findings, course of the disease, and the presence of cytoplasmic inclusions, indicating lysosomal storage phenomenon, suggest that the patients suffer from a genetic lysosomal storage disorder not described earlier. The eponym "Salla disease" was introduced, referring to the geographically restricted area where the family resides.