Ultrastructural, neurological, and glycosaminoglycan abnormalities in Lowe's syndrome

Wisniewski, Krystyna E.; Kieras, Fred J.; French, Joseph H.; Houck, George E.; Ramos, Peter L.

doi:10.1002/ana.410160109

Cited by 11 publications

(1 citation statement)

References 39 publications

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“…Interestingly, pathological studies have demonstrated single membrane bound, electron lucent vacuoles in OCRL deficient cells. Electron dense or membranous inclusions are only occasionally seen (Wisniewski et al , 1984). However, these inclusions are mainly derived from endosomes (Pirruccello and De, 2012).…”

Section: Diverse Functions Of Pi35p2 Kinases and Phosphatasesmentioning

confidence: 99%

Fig4 deficiency: A newly emerged lysosomal storage disorder?

Martyn

2013

Progress in Neurobiology

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FIG4 (Sac3 in mammals) is a 5’-phosphoinositide phosphatase that coordinates the turnover of phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), a very low abundance phosphoinositide. Deficiency of FIG4 severely affects the human and mouse nervous systems by causing two distinct forms of abnormal lysosomal storage. The first form occurs in spinal sensory neurons, where vacuolated endolysosomes accumulate in perinuclear regions. A second form occurs in cortical/spinal motor neurons and glia, in which enlarged endolysosomes become filled with electron dense materials in a manner indistinguishable from other lysosomal storage disorders. Humans with a deficiency of FIG4 (known as Charcot-Marie-Tooth disease type 4J or CMT4J) present with clinical and pathophysiological phenotypes indicative of spinal motor neuron degeneration and segmental demyelination. These findings reveal a signaling pathway involving FIG4 that appears to be important for lysosomal function. In this review, we discuss the biology of FIG4 and describe how the deficiency of FIG4 results in lysosomal phenotypes. We also discuss the implications of FIG4/PI(3,5)P2 signaling in understanding other lysosomal storage diseases, neuropathies, and acquired demyelinating diseases.

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Section: Diverse Functions Of Pi35p2 Kinases and Phosphatasesmentioning

confidence: 99%

Fig4 deficiency: A newly emerged lysosomal storage disorder?

Martyn

2013

Progress in Neurobiology

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Central nervous system and renal investigations in patients with Lowe syndrome

1992

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We describe three patients with Lowe (oculocerebrorenal) syndrome, emphasizing primarily the central nervous system and renal pathology. Using magnetic resonance imaging, we noted diffuse high T2 signals periventricularly, indicating significant white matter destruction, which may be responsible in part for the mental retardation, seizure disorder, hypotonia, and areflexia observed in the patients. In contrast to previously published reports, there was minimal renal tubular dysfunction; however, proteinuria was significantly increased in all patients. We believe that the observed proteinuria is primarily the result of glomerular pathology rather than renal tubular dysfunction and may represent a net loss of negative charges within the glomerular filter. This loss of charge may be linked to the increased excretion of glycosaminoglycans in the urine.

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