Oculocerebrorenal Dystrophy (Lowe Syndrome) Workup

Updated: Apr 24, 2018
  • Author: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Laboratory Studies

The studies discussed below 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 and serum 25 hydroxy vitamin D level

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.

Vitamin D deficiency due to lower exposure to sun is common in children and may worsen bone disease

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 inositol polyphosphate 5-phosphatase enzyme activity in cultured skin fibroblasts has been the preferred diagnostic test. Mutation analysis may be confirmatory and is increasingly used as the main diagnostic test. Few cases have been reported in females, who are more frequently carriers, with up to two-thirds of phenotypically significant cases secondary to a maternal carrier. Most affected females have X-autosomal translocations involving the OCRL1 locus with cytogenetic abnormalities (reciprocal translocation involving the X-chromosome), a 45,X karyotype, a uniparental disomy, or an extremely skewed X-inactivation, which subsequently permits full expression of the OCRL phenotype.


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.


Histologic Findings

Renal biopsies have demonstrated initial normal pathology with progression to tubular dilation around age 1-2 years and then subsequent increased glomerular cellularity, proteinaceous casts in tubular lumina, and focal glomerular sclerosis, as well as diffuse tubulointerstitial fibrosis in older children.