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

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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.

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References

  1. 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.

    CAS  Google Scholar 

  2. Bökenkamp A, Ludwig M. The oculocerebrorenal syndrome of Lowe: an update. Pediatr Nephrol. 2016;31(12):2201–12.

    Article  Google Scholar 

  3. 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.

    Article  CAS  Google Scholar 

  4. 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.

    Article  CAS  Google Scholar 

  5. 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.

    Article  CAS  Google Scholar 

  6. 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.

    Article  Google Scholar 

  7. 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.

    Article  CAS  Google Scholar 

  8. 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.

    CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 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.

    Article  CAS  Google Scholar 

  13. Pirruccello M, De Camilli P. Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL. Trends Biochem Sci. 2012;37(4):134–43.

    Article  CAS  Google Scholar 

  14. 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.

    Article  CAS  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. 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.

    Article  Google Scholar 

  17. Abbassi V, Lowe CU, Calcagno PL. Oculo-cerebro-renal syndrome. A review. Am J Dis Child. 1968;115(2):145–68.

    Article  CAS  Google Scholar 

  18. Tricot L, Yahiaoui Y, Teixeira L, et al. End-stage renal failure in Lowe syndrome. Nephrol Dial Transplant. 2003;18(9):1923–5.

    Article  Google Scholar 

  19. 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.

    Article  CAS  Google Scholar 

  20. 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.

    Chapter  Google Scholar 

  21. 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.

    PubMed  Google Scholar 

  22. 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.

    Article  CAS  Google Scholar 

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Acknowledgements

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.

Funding

This research was not supported by any funds.

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Authors and Affiliations

  1. Department of Pediatrics, Minoh City Hospital, 5-7-1 Kayano, Minoh City, Osaka, 562-8562, Japan

    Katsusuke Yamamoto, Yasuhiro Hasegawa, Yasuhisa Ohata, Yoshimi Mizoguchi, Tsunesuke Shimotsuji & Takehisa Yamamoto

  2. Department of Pediatric Nephrology and Metabolism, Osaka Women’s and Children’s Hospital, 840 Murodo, Izumi City, Osaka, 594-1101, Japan

    Katsusuke Yamamoto & Kenichi Satomura

  3. Department of Pediatrics, Osaka University Graduate School of Medicine, 1-1 Yamadaoka, Suita City, Osaka, 565-0873, Japan

    Yasuhisa Ohata

  4. Division of Internal Medicine, Meisei Daini Hospital, 1-19-20, Higashi-Obase, Higashinari, Osaka City, Osaka, 537-0024, Japan

    Kenichi Satomura

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  1. Katsusuke Yamamoto
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  2. Yasuhiro Hasegawa
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  3. Yasuhisa Ohata
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  4. Kenichi Satomura
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  5. Yoshimi Mizoguchi
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  6. Tsunesuke Shimotsuji
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  7. Takehisa Yamamoto
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Correspondence to Takehisa Yamamoto.

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Yamamoto, K., Hasegawa, Y., Ohata, Y. et al. Complete oculocerebrorenal phenotype of Lowe syndrome in a female patient with half reduction of inositol polyphosphate 5-phosphatase. CEN Case Rep 9, 95–100 (2020). https://doi.org/10.1007/s13730-019-00434-z

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  • DOI: https://doi.org/10.1007/s13730-019-00434-z

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