title: Renal involvement in patients with mucolipidosis IIIalpha/beta: Causal relation or co-occurrence?
abstract: Mucolipidosis IIIalpha/beta (MLIIIalpha/beta) is a rare lysosomal storage disorder characterized by childhood onset of flexion contractures of fingers, joint stiffness in the shoulders, hips, and knees, and mild short stature. Recessive mutations in the GNPTAB gene have been associated with MLIIIalpha/beta. We present five children aged 9-16 years from a large kindred family whose serum activities of several lysosomal enzymes were significantly elevated. Whole exome sequencing followed by confirmation by Sanger sequencing identified a novel homozygous missense mutation (c.22 A > G; p.R8G) in the GNPTAB gene in all affected subjects. The five patients initially presented with flexion contractures of fingers followed by stiffnes of large joints. Only two affected boys also had a nephrotic-range proteinuria. Renal biopsy showed focal segmental glomerulosclerosis and foamy appearance of glomerular visceral epithelial cells which were compatible with storage disease. No other known causes of proteinuria could be detected by both laboratory and biopsy findings. There was no known family history of hereditary kidney disease, and healthy siblings and parents had normal renal function and urinalysis. These findings suggest that the renal involvement probably due to MLIIIalpha/beta, although it can still be present by coincidence in the two affected patients.
authors.affiliation: Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tüysüz
authors.affiliation: Department of Neurosurgery, Program on Neurogenetics, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Adife Gülhan
authors.initials: AG
authors.lastname: Ercan-Sencicek
authors.affiliation: Department of Pediatric Nephrology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Nur
authors.initials: N
authors.lastname: Canpolat
authors.affiliation: Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Asuman
authors.initials: A
authors.lastname: Koparır
authors.affiliation: Department of Neurosurgery, Program on Neurogenetics, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Saliha
authors.initials: S
authors.lastname: Yılmaz
authors.affiliation: Department of Pathology, Istanbul Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Işın
authors.initials: I
authors.lastname: Kılıçaslan
authors.affiliation: Department of Neurosurgery, Program on Neurogenetics, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Burcu
authors.initials: B
authors.lastname: Gülez
authors.affiliation: Department of Neurosurgery, Program on Neurogenetics, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Kaya
authors.initials: K
authors.lastname: Bilguvar
authors.affiliation: Department of Neurosurgery, Program on Neurogenetics, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Murat
authors.initials: M
authors.lastname: Günel
mesh_terms: D000293:Adolescent; D001483:Base Sequence / Q000235:genetics; D002648:Child; D059472:Exome; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental; D006720:Homozygote; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D009081:Mucolipidoses / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense; D010375:Pedigree; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics*
chemical_list: D017855:Transferases (Other Substituted Phosphate Groups); C511050:GNPTAB protein, human
keywords: GNPTAB gene; mucolipidosis IIIalpha/beta; renal involvement