Lowe Syndrome - Oculocerebrorenal Dystrophy

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Described in 1952 by Lowe et al. (MGH, Boston, USA)


Contents

Diagnosis

Diagnostic Triad:

  1. Congenital cataracts
  2. Hypotonia and subsequent learning disability
  3. Fanconi Syndrome renal tubular dysfunction

Diagnostic test:

  • Fibroblast culture with enzyme activity assay.
  • Mutation analysis may confirm diagnosis.


Other clinical features:

  • Hypotonia and cataracts are usually present at birth. Chronic kidney disease becomes evident from the second decade of life.
  • Seizures occur in 50% of children. Most have significant learning difficulties. 10% may be mild.
  • Bilateral glaucoma occurs in 50% within the first year.
  • Deep tendon reflexes may be absent. Hypotonia leads to scoliosis and hernias in many cases.
  • Bone disease with fractures occurs due to the Fanconi Syndrome (variable severity).

Incidence

Estimated at 1 in 500 000 (all ethnicities). Very few cases have been reported in females.


Pathophysiology

X-linked defect of OCRL1 gene (Chromosome Xq26), whose protein is located in the Golgi apparatus and appears to be involved in cytoskeleton remodelling and cellular trafficking. Several mutations have been found, often with germline mosaicism.

OCRL1 protein is a phosphatidyl-inositol bisphosphate phosphatase.


Morbidity, Mortality and Prognosis

A high mortality in the first few months is usually due to severe metabolic derangement secondary to the Fanconi Syndrome.

Death usually occurs in the second or third decade of life.

Specific problems:

  • Pneumonia secondary to hypotonia and poor cough reflex
  • Dehydration (poor water retention), electrolyte imbalance and severe metabolic acidosis
  • Status epilepticus

Investigations

Diagnostic test:

  • Fibroblast culture with enzyme activity assay.
  • Mutation analysis may confirm diagnosis.


Other laboratory tests:

  • Urine: electrolytes, osmolality, amino acids, carnitine
    • Bicarbonate loss causing proximal renal tubular acidosis
    • Aminoaciduria, phosphaturia, proteinuria, hypercalciuria
    • Water resorption impaired (dehydration may be life-threatening)
    • L-carnitine in urine
  • Plasma
    • Hypokalaemia may require correction
    • Alkaline phosphatase may indicate developing rickets
    • Carnitine: may be low requiring replacement due to urinary loss
    • Creatinine and clearance: progressive renal failure
  • Blood gas
    • Metabolic acidosis due to renal bicarbonate loss


Imaging

  • MRI brain: peri-ventricular white matter fluid filled cysts (no clinical significance)
  • Renal USS: may show nephrocalcinosis / nephrolithiasis
  • Plain XRs: typical signs of rickets may be seen.


References

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