Oculocerebrorenal syndrome

Oculocerebrorenal syndrome
ICD-10	E72.0
ICD-9	270.8
OMIM	309000
DiseasesDB	29146
eMedicine	oph/516
MeSH	D009800

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]

Overview

Oculocerebrorenal syndrome (also called Lowe syndrome) is a X-linked recessive disorder characterized by hydrophthalmia, cataracts, mental retardation, aminoaciduria, reduced renal ammonia production and vitamin D-resistant rickets.

Historical Perspective

It is named after Charles Upton Lowe, who was the first to describe the condition.

Pathophysiology

• Mutation in the OCRL gene leads to membrane defects which results in inability of proximal tubular cells to reabsorb low molecular weight proteins, bicarbonates and phosphorus.
• There is impaired intra-cellular protein folding and sorting, especially in polarized cells like renal epithelium and optic lens. This explains the pathogenesis of renal dysfunction and cataract.

Genetics

It is associated with mutation in the gene OCRL.

Differentiating Oculocerebrorenal syndrome from other diseases

Differential diagnosis

• Cystinosis
• Fanconi's syndrome
• Hypophosphatemic rickets

Epidemiology and Demographics

• Oculocerebrorenal syndrome is a rare disease with a prevalence of about 1 in 200,000 to 1 in every 500,000 births.

Sex

• As the disease follows an X-linked inheritance pattern, almost all affected patients are males. However, a few females with this condition have been reported.

Complications

• Muscle tone improves with age, but never comes back to normal.
• Scoliosis
• Hernias
• Osteopenia
• Osteoporosis
• Rickets
• Fractures
• Metabolic acidosis

Diagnosis

History

• Mental retardation
• Seizures
• Febrile seizures
• Behavioral disturbances
  • Temper tantrums
  • Aggression
  • Unusual repetitive movements
  • Irritability
  • Rigidity
  • Preoccupations and obsessions
• Constipation

Physical Examination

Appearance of the Patient

• Small eyes
• Frontal bossing
• Elongated face

Skin

• Cysts

Eyes

• Decreased visual acuity
• Cataract at birth
• Glaucoma with or without buphthalmos
• Keloidss over conjunctiva and cornea without preceding trauma
• Strabismus

Extremities

• Joint swelling: small and large joints
• Arthritis
• Tenosynovitis
• Joint contractures

Neurologic

• Generalized neonatal hypotonia
• Areflexia
• Feeding difficulty
• Delayed motor development
• Delayed milestones

Other

• Cryptorchidism
• Skin and mucosal cysts
• Delayed dentition
• Dental caries
• Gingival inflammation
• Dental cysts

Laboratory Findings

Urinalysis

• Low osmolarity
• Albuminuria
• Low molecular weight proteiuria: retinol binding protein, β2 microglobulin
• Bicarbonate loss
• Aminoaciduria
• Hypercalciuria
• Hyperphosphaturia
• Decreased creatinine clearance
• L-carnitine lost in urine

Blood Tests

• Raised ESR
• High alkaline phosphatase
• Blood gases:
  • Low bicarbonate levels
  • Compensatory decrease in PCO2 levels
• Raised serum creatinine levels
• Serum markers: Rise in
  • AST
  • LDH
  • Creatinine kinase
• Acid phosphatase
• T4, TSH levels increased

Other tests

• Measurement of enzyme activity in cultured fibroblasts is the preferred test for establishing diagnosis.

X ray

• Osteopenia
• Metaphyseal flarring and cupping

MRI

• Demyelination of white matter in the periventricular area

Ultrasonography

• Nephrocalcinosis
• Nephrolithiasis

Treatment

Ocular

• Glaucoma:
  • Patients should be monitored for glaucoma
  • Intraocular pressure lowering agents
  • Surgery: trabeculotomy, drainage filtration device
• Corneal keloids:
  • Topical steroids, lubricants
  • Lamellar keratectomy, corneal transplant
• Strabismus and refraction errors must be corrected.
• Catarcts should be surgically removed, preferably in the first 6 months of life, to prevent development of amblyopia. Aphakic correction must follow the surgery.

Renal function

• Must be monitored to look for development of renal failure, tubular wasting
• Blood pH and electrolytes should be followed up.

Neurologic symptoms

• Seizures should be treated with appropriate anticonvulsants.

Diet

• Phosphate supplements
• Carnitine replacement
• Vitamin D supplementation

Behavioral therapy

• Behavioral modification for maladaptive behavioral patterns

Others

• Speech therapy and occupational therapy may be initiated as needed.

References

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