Oculocerebrorenal Syndrome of Lowe



Oculocerebrorenal Syndrome of Lowe


Ami Bhalodia, MD





Key Facts


Terminology



  • Oculocerebrorenal syndrome (OCRL)


Etiology/Pathogenesis



  • Inherited mutation caused by OCRL1 gene mutation


  • Affects protein trafficking and cellular metabolism


Clinical Issues



  • X-linked disorder; 1:200,000-1:500,000 births


  • Proximal tubular dysfunction, congenital cataracts, and cognitive impairment


Microscopic Pathology



  • Tubular and interstitial abnormalities most frequent



    • Dilated tubules with protein casts


    • Tubular atrophy and interstitial fibrosis


    • Medullary nephrocalcinosis


  • Glomerular disease is rare



    • Diffuse mesangial sclerosis


Ancillary Tests



  • Electron microscopy



    • Dilated proximal tubular infolding


    • Proximal tubular basement membrane lamellar thickening


    • Tubular mitochondrial swelling and irregularity


    • Irregular glomerular basement membrane thickening


Top Differential Diagnoses



  • Dent disease


  • Cystinosis


  • Fanconi syndrome


  • Hypophosphatemic rickets







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.


TERMINOLOGY


Abbreviations



  • Oculocerebrorenal syndrome of Lowe (OCRL)


Synonyms



  • Oculocerebrorenal dystrophy


Definitions



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


ETIOLOGY/PATHOGENESIS


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


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 1:200,000-1:500,000 births


    • Pan-ethnic disorder


  • Gender



    • Almost all males


    • Females with X-autosomal translocations reported


Presentation



  • 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


Treatment



  • Renal tubular acidosis



    • Monitor acid-base status and electrolyte levels



      • Potassium and calcium supplementation


      • ˜ 50% require bicarbonate supplementation

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

Full access? Get Clinical Tree
Get Clinical Tree app for offline access