Oculocerebrorenal Dystrophy (Lowe Syndrome) Workup

  • Author: Amira Al-Uzri, MD, MCR; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 27, 2012
 

Laboratory Studies

The following studies may be indicated in oculocerebrorenal syndrome of Lowe (OCRL), or Lowe syndrome:

  • Urinalysis, urinary electrolyte levels (including urine phosphorous and calcium levels), urinary amino acid levels, urine osmolality, and urinary carnitine levels
    • Renal tubular dysfunction (commonly described as Fanconi syndrome) is a cardinal manifestation of Lowe syndrome, but severity widely varies.
    • Proximal renal tubular acidosis due to bicarbonate loss in the urine has been reported.
    • Aminoaciduria varies in Lowe syndrome but is typically present.
    • Low molecular weight (LMW) proteinuria, such as retinol-binding protein and β2 microglobulin, are elevated in urine.
    • Albuminuria may be noted.
    • Hypercalcuria has been reported in patients with Lowe syndrome as part of the proximal tubulopathy or as a result of vitamin D treatment, leading to nephrocalcinosis or nephrolithiasis/urolithiasis.
    • Water resorption is impaired, resulting in high urine volume and low urine osmolality. Dehydration may be life threatening in the first years of life.
    • Hyperphosphaturia may lead to osteomalacia or rickets.
    • L-carnitine is lost in the urine. Whether carnitine wasting in the urine from severe Fanconi syndrome is the etiology of carnitine deficiency has not been studied adequately in Lowe syndrome.
    • Glycosuria is absent in the majority of patients with Lowe syndrome.
  • Plasma electrolyte levels
    • Clinically significant hypokalemia due to urinary losses is rare but may require replacement therapy.
    • Clinically significant hyponatremia and hypocalcemia are extremely rare.
  • Plasma alkaline phosphatase, calcium, and phosphorus levels
    • Urinary losses of calcium and phosphorus predispose to the development of rickets and osteomalacia.
    • A rise in alkaline phosphatase levels is usually the first biochemical indicator of rickets.
  • Blood gas levels: Significant metabolic acidosis is caused by the urinary loss of bicarbonate.
  • Plasma carnitine levels: As carnitine is lost in the urine, plasma levels may be low and oral replacement therapy may be necessary.
  • Plasma creatinine levels and estimation of creatinine clearance: Progressive renal failure is heralded by a gradual increase in plasma creatinine and a decrease in creatinine clearance. The calculated glomerular filtration rate (GFR) using widely published formulas such as the Schwartz or the Schwartz Haycock formulas in children with Lowe syndrome were found to overestimate the true GFR due to low muscle mass. A lower k value in the corresponding formulas was suggested for use in patients with Lowe syndrome; for example, a k of .30 is used when creatinine is measured in mg/dL, and a k of 26 is used when creatinine is measured in mmol/L. Direct measurement of GFR using a renal glomerular marker such as iohexol or iothalamate is the preferred and accurate method to measure kidney function in patients with Lowe syndrome.
  • Other serum markers
    • Serum aspartate aminotransferase (AST), LDH, and creatine kinase levels are often elevated. AST and LDH levels may be 2-3 times the reference range.
    • Serum acid phosphatase levels may be elevated.
    • α -2 globulin levels may be abnormally elevated on serum protein electrophoresis findings.
    • Thyroxine (T4) levels, thyroxine-binding globulin (TBG) levels, and erythrocyte sedimentation rate (ESR) may be high.
    • Thrombocytopenia has been reported in Lowe syndrome and can be explained by the homology of the human OCRL protein to the phosphatidylinositol biphosphate 5-phosphatase present in human platelets, resulting in some functional overlap between these proteins.
  • Diagnostic testing: Measurement of enzyme activity in cultured fibroblasts has been the preferred diagnostic test. Mutation analysis may be confirmatory and is increasingly used as the main diagnostic test.
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Imaging Studies

  • Brain MRI may demonstrate white matter abnormalities, particularly in the periventricular area. These signal abnormalities are caused by fluid-filled cysts, which appear to have no clinical significance. Tigroid pattern of white matter demyelination has been reported on MRI imaging and is thought to represent areas of normal white matter signaling interspersed with demyelinated areas.
  • Radiographs of the wrists and long bones may demonstrate changes that are typical of rickets, including metaphyseal flaring and osteopenia.
  • Renal imaging studies include the following:
    • Renal ultrasonography may show evidence of nephrocalcinosis or even nephrolithiasis.
    • Poor renal uptake of technetium 99 m (Tc99m) dimercaptosuccinic acid is reported in patients with Lowe syndrome.
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Histologic Findings

  • Typical renal findings include atrophic tubular epithelial cells and interstitial fibrosis.
  • The tubular lumina may be filled with proteinaceous material.
  • In older patients, the glomerular basement membranes appear thickened with fusion of the podocytes. In later stages of the disease, sclerosis of the glomeruli is evident.
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Contributor Information and Disclosures
Author

Amira Al-Uzri, MD, MCR  Associate Professor of Pediatrics, Director, Pediatric Clinical Research Office, Director, Pediatric Clinical and Translational Research Center, Department of Pediatrics, Divison of Pediatric Kidney Services and Hypertension, Oregon Health and Science University School of Medicine

Amira Al-Uzri, MD, MCR is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology, and American Society of Transplantation

Disclosure: Nothing to disclose.

Coauthor(s)

Robert D Steiner, MD  Credit Unions for Kids Professor of Pediatric Research, Professor of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Faculty, Program in Molecular and Cellular Biosciences, Oregon Health and Science University School of Medicine; Attending Physician, Doernbecher Children's Hospital; Staff Consultant, Director of Metabolic Bone Disease Clinic, Shriners Hospital Portland

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

Melissa P Wasserstein, MD  Associate Professor, Departments of Genetics and Genomic Sciences and Pediatrics, Mount Sinai School of Medicine

Melissa P Wasserstein, MD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Cydney L Fenton, MD  Director, Center for Diabetes and Endocrinology, Akron Children's Hospital

Cydney L Fenton, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Ian Krantz, MD  Department of Pediatrics, Assistant Professor, University of Pennsylvania and Children's Hospital of Philadelphia

Ian Krantz, MD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Leonard G Feld, MD, PhD, MMM, FAAP  Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center

Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International

Disclosure: Nothing to disclose.

Daniel Rauch, MD, FAAP  Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine

Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine

Disclosure: Baxter Honoraria Consulting

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

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The classic lenticular opacities in a female carrier for Lowe syndrome. Note the punctate cortical opacities in radical wedges. (Photo courtesy of Otis Paul, MD)
 
 
 
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