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.
This is a preview of subscription content, log in to check access.
We are grateful to the past Dr. Youichi Mizusawa at Tokyo Medical and Dental University for enzyme assays and the past Dr. Takashi Sekine at The University of Tokyo for genetic investigations. We also thank Dr. Makoto Ishida at Ishida Clinic and Dr. Hidehito Kondou at Japanese Red Cross Kyoto Daiichi Hospital for useful discussions and Dr. Mai Ihashi, other pediatricians, and many medical staff working in Minoh City Hospital for their clinical co-operation.
This research was not supported by any funds.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from patient and her parent included in the study.
Lowe CU, Terrey M, MacLachlan EA. Organic-aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation; a clinical entity. Am J Dis Child. 1952;83(2):164–84.Google Scholar
Bökenkamp A, Ludwig M. The oculocerebrorenal syndrome of Lowe: an update. Pediatr Nephrol. 2016;31(12):2201–12.CrossRefGoogle Scholar
Hichri H, Rendu J, Monnier N, et al. From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes. Hum Mutat. 2011;32(4):379–88.CrossRefGoogle Scholar
Recker F, Reutter H, Ludwig M. Lowe syndrome/Dent-2 disease: a comprehensive review of known and novel aspects. J Pediatr Genet. 2013;2(2):53–68.CrossRefGoogle Scholar
Uemura O, Nagai T, Ishikura K, et al. Creatinine-based equation to estimate the glomerular filtration rate in Japanese children and adolescents with chronic kidney disease. Clin Exp Nephrol. 2014;18:626–33.CrossRefGoogle Scholar
Sekine T, Nozu K, Iyengar R, et al. OCRL1 mutations in patients with Dent disease phenotype in Japan. Pediatr Nephrol. 2007;22(7):975–80.CrossRefGoogle Scholar
Zhang X, Jefferson AB, Auethavekiat V, Majerus PW. The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase. Proc Natl Acad Sci USA. 1995;92(11):4853–6.CrossRefGoogle Scholar
Svorc JM, Masopust J, Komárková A, Macek M, Hyánek J. Oculocerebrorenal syndrome in a female child. Am J Dis Child. 1967;114(2):186–90.PubMedGoogle Scholar
Harris LS, Gitter KA, Galin MA, Plechaty GP. Oculo-cerebro-renal syndrome. Report of a case in a baby girl. Br J Ophthalmol. 1970;54(4):278–80.CrossRefGoogle Scholar
Hodgson SV, Heckmatt JZ, Hughes E, Crolla JA, Dubowitz V, Bobrow M. A balanced de novo X/autosome translocation in a girl with manifestations of Lowe syndrome. Am J Med Genet. 1986;23(3):837–47.CrossRefGoogle Scholar
Mueller OT, Hartsfield JK, Gallardo LA, et al. Lowe oculocerebrorenal syndrome in a female with a balanced X;20 translocation: mapping of the X chromosome breakpoint. Am J Hum Genet. 1991;49(4):804–10.PubMedPubMedCentralGoogle Scholar
Cau M, Addis M, Congiu R, et al. A locus for familial skewed X chromosome inactivation maps to chromosome Xq25 in a family with a female manifesting Lowe syndrome. J Hum Genet. 2006;51(11):1030–6.CrossRefGoogle Scholar
Pirruccello M, De Camilli P. Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL. Trends Biochem Sci. 2012;37(4):134–43.CrossRefGoogle Scholar
Suchy SF, Olivos-Glander IM, Nussabaum RL. Lowe syndrome, a deficiency of phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi apparatus. Hum Mol Genet. 1995;4(12):2245–50.CrossRefGoogle Scholar
Wu G, Zhang W, Na T, Jing H, Wu H, Peng JB. Suppression of intestinal calcium entry channel TRPV6 by OCRL, a lipid phosphatase associated with Lowe syndrome and Dent disease. Am J Physiol Cell Physiol. 2012;302(10):C1479–1491.CrossRefGoogle Scholar
Monserrat L, Gimeno-Blanes JR, Marín F, et al. Prevalence of fabry disease in a cohort of 508 unrelated patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2007;50(25):2399–403.CrossRefGoogle Scholar
Abbassi V, Lowe CU, Calcagno PL. Oculo-cerebro-renal syndrome. A review. Am J Dis Child. 1968;115(2):145–68.CrossRefGoogle Scholar
Tricot L, Yahiaoui Y, Teixeira L, et al. End-stage renal failure in Lowe syndrome. Nephrol Dial Transplant. 2003;18(9):1923–5.CrossRefGoogle Scholar
Witzleben CL, Schoen EJ, Tu WH, McDonald LW. Progressive morphologic renal changes in the oculo-cerebro-renal syndrome of Lowe. Am J Med. 1968;44(2):319–24.CrossRefGoogle Scholar
Nakanishi K, Yoshikawa N. Immunoglobulin a nephropathies in children (includes HSP). In: Avner ED, Harmon WE, Niaudet P, editors. Pediatric nephrology. Springer: Heidelberg; 2016. p. 983–1033.CrossRefGoogle Scholar
Schena FP, Cerullo G, Rossini M, Lanzilotta SG, D’Altri C, Manno C. Increased risk of end-stage renal disease in familial IgA nephropathy. J Am Soc Nephrol. 2002;13(2):453–60.PubMedGoogle Scholar
Hodgson SV, Heckmatt JZ, Hughes E, Crolla JA, Dubowitz V, Bobrow M. A balanced de novo X/autosome translocation in a girl with manifestations of Lowe syndrome. Am J med Genet. 1986;23:837–47.CrossRefGoogle Scholar