Complete oculocerebrorenal phenotype of Lowe syndrome in a female patient with half reduction of inositol polyphosphate 5-phosphatase

Abstract

The oculocerebrorenal disorder of Lowe syndrome is an X-linked mutation in the gene oculocerebrorenal syndrome of Lowe 1 (OCRL), characterized by the triad of congenital cataracts, severe intellectual impairment, and renal tubular dysfunction. Manifestations of phenotype in female carriers and patients are extremely rare. We present a female case with congenital cataracts, severe intellectual impairment, sensorineural hearing loss, and renal tubular dysfunction as Lowe syndrome. A 9-year-old Japanese girl visited our hospital due to prolonged proteinuria. Her renal biopsy revealed diffuse mesangium proliferation, sclerosis and dilatation of renal tubules, and mild IgA deposition in the mesangial region. Furthermore, she had congenital cataracts, severe intellectual impairment, and sensorineural hearing loss. Genetic screening did not identify mutations of the ORCL gene encoding inositol polyphosphate 5-phosphatase (IPP-5P) (46 XX, female). However, we found the reduction of enzyme activity of IPP-5P to 50% of the normal value. Furthermore, her renal function had deteriorated to renal failure within a decade. Finally, she received peritoneal dialysis and renal transplantation. We present the oculocerebrorenal phenotype of Lowe syndrome in a female patient with reduced activity of IPP-5P without OCRL gene mutation.

An Update on the Oculocerebrorenal Syndrome of Lowe: A Review Article

“…The life duration of LS is not exceeded more than 40 years, and prenatal diagnosis and prevention of complications are essential. The LS was first described in 1952 by Lowe et al The LS's other name is known as a phosphatidylinositol-4,5-bisphosphate-5-phosphatase deficiency or oculocerebrorenal (OCRL) syndrome (1)(2)(3). The OCRL syndrome's name roots in the fact that the three main parts of the body are prominently preoccupied (i.e., eyes, brain, and kidney).…”

“…Still, it is likely that musculoskeletal, gonad, skin, and connective tissues are also involved (4)(5)(6). This syndrome is a sex-linked disorder, the main features of which are the triad of renal tubular dysfunction, mental disability, and cataracts (1)(2)(3)(4)(5)(6). Other characteristics include growth retardation after birth with no dependence on kidney function, behavioral problems, stereotypic behavior, areflexia, severe muscular hypotonia, intellectual disability, recurrent pathologic bone fracture, nontender joint swelling, tenosynovitis, arthritis, debilitating palmar and plantar fibrosis, focal nodules, bone erosions, potassium loss, sodium loss, aminoaciduria, bicarbonaturia, low-molecular-weight (LMW) proteinuria, tubular dysfunction with slowly progressive renal insufficiency, and arthropathy (1,2,(7)(8)(9).…”

“…Recently, no relationship has been identified between genotypes and phenotypes; therefore, the clinical intensity of disease is correlated with some types of disease. However, male patients within the same family have equivalent phenotypes, as interfamilial variability has not yet been reported (3,4,11). Dent disease is an X chromosomedependent inheritance tubulopathy with proximal renal tubular acidosis, hypercalciuria, nephrocalcinosis, renal stone, LMW proteinuria, renal failure, and hypophosphatemic rickets.…”

“…Dent disease is an X chromosomedependent inheritance tubulopathy with proximal renal tubular acidosis, hypercalciuria, nephrocalcinosis, renal stone, LMW proteinuria, renal failure, and hypophosphatemic rickets. Patients with Dent disease never have extrarenal manifestations, except rickets (3,4,14). This study aimed to assess the clinical manifestations of LS, mainly the novel investigations of LS, to provide an update on the clinical manifestations that diminished the misdiagnosis of LS.…”