1. ¹Department of Pediatrics, Ayabe Municipal Hospital, Ayabe, Japan
2. ²Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan
3. ³Supra-Biomolecular Research System, RIKEN Frontier Research System, RIKEN, Wako, Japan
4. ⁴Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
5. ⁵Department of Anatomy, Nihon University School of Medicine, Tokyo, Japan
6. ⁶Division of Medicinal Biotechnology, Institute of Medical Resources, Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan
7. ⁷Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan

Correspondence: Hitoshi Sakuraba, Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan. Fax: +81-3-38236008. E-mail: sakuraba@rinshoken.or.jp

Received 27 July 2004; Accepted 6 September 2004; Published online 13 November 2004.

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 thin-layer 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.