Oculocerebrorenal syndrome
Synonyms and keywords: Lowe's syndrome

# Overview
Oculocerebrorenal 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.

# Classification

# 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.

# Causes

# 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.

# Risk Factors

# Screening

# Natural History, Complications, and Prognosis
- Muscle tone improves with age, but never comes back to normal.
- Scoliosis
- Hernias
- Osteopenia
- Osteoporosis
- Rickets
- Fractures
- Metabolic acidosis

# Diagnosis

## History and Symptoms
- Mental retardation
- Seizures
- Febrile seizures
- Behavioral disturbances
Temper tantrums
Aggression
Unusual repetitive movements
Irritability
Rigidity
Preoccupations and obsessions
- 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, 2 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
- Low bicarbonate levels
- Compensatory decrease in PCO2 levels
- Raised serum creatinine levels
- Serum markers: Rise in
AST
LDH
Creatinine kinase
- 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
- Patients should be monitored for glaucoma
- Intraocular pressure lowering agents
- Surgery: trabeculotomy, drainage filtration device
- Corneal keloids:
Topical steroids, lubricants
Lamellar keratectomy, corneal transplant
- 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.

## Prevention