Oculocerebrorenal Syndrome of Lowe

Oculocerebrorenal Syndrome of Lowe

Ami Bhalodia, MD

This proximal convoluted tubule in a patient with Lowe syndrome shows marked thickening of the tubular basement membrane. There is also prominent tubular basement membrane lamellar image alteration.

This proximal convoluted tubule in a patient with Lowe syndrome shows prominent dilatation of the tubular infolding image and marked tubular basement membrane lamellar image alteration.



  • Oculocerebrorenal syndrome of Lowe (OCRL)


  • Oculocerebrorenal dystrophy


  • Disease triad of renal tubular dysfunction, congenital cataracts, and mental retardation due to mutations in OCRL (OMIM #309000)


X-linked Genetic Disease

  • Mutations in OCRL gene (Xq26.1)

    • Heterogeneous: Premature stop codons, insertion/deletion, splice site, and missense mutations

  • OCRL encodes OCRL1 protein

    • Phosphatidylinositol 4,5-biphosphate 5-phosphatase

    • Binds to clathrin

      • Regulates clathrin-mediated protein trafficking

    • Affects vesicle-dependent proximal tubule reabsorption and trafficking of transporter proteins

      • Small molecular weight proteins, albumin, aminoacids, bicarbonate, calcium

      • Lysosomal enzymuria due to altered trafficking

      • Glucose transport not affected



  • Incidence

    • 1:200,000-1:500,000 births

    • Pan-ethnic disorder

  • Gender

    • Almost all males

    • Females with X-autosomal translocations reported


  • Hypotonia and cataracts at birth

    • Glaucoma (˜ 50%)

  • Severe mental retardation (˜ 33%)

    • Seizures (˜ 50%)

  • Metabolic acidosis

    • Bicarbonate wasting, moderate

    • Not Fanconi syndrome, no glycosuria, mild phosphaturia

  • Low-grade proteinuria

  • Chronic renal disease by 2nd decade

  • Cryptorchidism

Laboratory Tests

  • Hypokalemia, hypocalcemia, low bicarbonate

  • Assessment of proximal tubular function

    • Low molecular weight proteinuria (e.g., retinol binding protein) (100%)

    • Lysosomal enzymuria (N-acetyl-β-d-glucosaminidase) (100%)

    • Generalized aminoaciduria (˜ 90%)

    • Hypercalcuria (˜ 95%)

  • Increased alkaline phosphatase

  • Genetic tests for OCRL mutations


  • Renal tubular acidosis

    • Monitor acid-base status and electrolyte levels

      • Potassium and calcium supplementation

      • ˜ 50% require bicarbonate supplementation

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Oculocerebrorenal Syndrome of Lowe

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