Clinical, biochemical, and cytochemical studies on a Japanese Salla disease case associated with a renal disorder

Abstract

We report the first Japanese case of Salla disease. A 5-year-old male patient developed unique proteinuria with other clinical manifestations, including coarse facies, dysostosis multiplex, mild mitral valve regurgitation, umbilical and inguinal herniation, and mild developmental delay. Pathological analysis of biopsied kidney tissues showed marked vacuolation of podocytes, mesangial cells, capillary endothelial cells, and tubular cells. Biochemical studies involving thinlayer chromatography and mass spectrometry revealed increased excretion of free sialic acid (N-acetylneuraminic acid) into the patient's urine. Immuno-and lectin staining of the patient's cells demonstrated the accumulation of sialyl and asialyl glycoconjugates in lysosomes and late endosomes. A defect in sialyl glycoconjugate metabolism is thought to have occurred in the patient's cells, besides impairment of the lysosomal transport of free sialic acid residues. A renal disorder should be considered as an important manifestation, not only in infantile free sialic acid storage disease but also in Salla disease.

Testing the feasibility of fully automated chip‐based nanoelectrospray ionization mass spectrometry as a novel tool for rapid diagnosis of Fabry disease

“…In recent years, MS based on either ESI or MALDI alone or in conjunction with separation techniques such as CE and HPLC was demonstrated as one of the most proficient analytical tools for studies targeting LSDs. Gaucher, Pompe, Fabry, Niemann‐Pick, Krabbe, Schindler, Salla, and Kanzaki diseases and the classes of mucopolysaccharidoses and gangliosidoses were all approached at the molecular level using MS and MS/MS strategies .…”