PEDBASE.org - The Pediatric Database - Detailed information of LOWE (OCULO-CEREBRO-RENAL) SYNDROME

LOWE (OCULO-CEREBRO-RENAL) SYNDROME

DEFINITION:

An x-linked recessive disorder of unknown etiology resulting in an ocular, cerebral, and renal syndrome.

EPIDEMIOLOGY:

incidence: rare (about 50 cases worldwide)
age of onset:
- newborn (hypotonia, cataracts)
risk factors:
- familial - x-linked recessive
  - chrom.#: Xq26.1
  - gene: ?
- M >> F

PATHOGENESIS:

1. Background

Lowe Syndrome first described in 1952

2. Genetic Defect

genetic defect -> ? derangement in connective tissue metabolism
prenatal phenotypic expression as infants born with hypotonia and cataracts
three distinct phases of syndrome:

1. Infancy

neurologic and ophthalmologic manifestations predominant with renal tubular dysfunction presenting within the first year of life

2. Childhood

renal tubular dysfunction -> failure to thrive, rickets

3. Late Childhood

death from inanition, pneumonia, chronic renal failure

CLINICAL FEATURES:

1. Ophthalmologic Manifestations

superficial granulations with corneal scarring
bilateral congenital cataracts (100%)
glaucoma +/- buphthalmos
miotic pupils
enophthalmos
visual problems -> nystagmus, blindness

2. Neurological Manifestations

infantile hypotonia
gross motor developmental delay
reduced or absent deep tendon reflexes
muscle wasting
moderate to severe mental retardation
- speech/language/communication disabilities

3. Renal Manifestations

1. Fanconi Syndrome

minimal expression at birth but increases in severity with age (usually present within the first year of life)
episodes of vomiting, dehydration, weakness, & unexplained fever
anorexia and constipation
polydipsia and polyuria
failure to thrive and growth failure
rickets

4. Others

craniosynostosis -> frontal bossing
cryptorchidism (bilateral)
hyperactivity with high-pitched scream
joint hypermobility -> joint contractures

INVESTIGATIONS:

1. Fanconi Syndrome

1. Serum

normal anion gap hyperchloremic metabolic acidosis (with low serum bicarbonate)
normal or low amino acids
normal glucose
hypophosphatemia, hypokalemia, hypouricemia
elevated alkaline phosphatase

2. Urine

generalized (non-specific) hyperaminoaciduria
- presents as early as 10 days of life
glucosuria, phosphaturia
pH <5.5 with a low specific gravity (hyposthenuria)
bicarbonaturia, hyperkaliuria, uricosuria, tubular proteinuria, carnitinuria, low urinary ammonia
progressive decrease in GFR

3. Renal Biopsy

progressive glomerular and interstitial fibrosis

2. Imaging Studies

1. CT/MRI

nonspecific abnormalites of central nervous system

3. EEG

diffuse abnormalities

MANAGEMENT:

1. Supportive

no treatment for syndrome
multidisciplinary approach
- Paediatrics - vitamin D supplements, correct metabolic acidosis, hypophosphatemia
- Neurology - moniter hypotonia and developmental delays
- Nephrology - moniter Fanconi Syndrome complications
- Ophthalmo. - moniter ophthalmological complications
- Genetics - genetic counselling, prenatal diagnosis (female carriers show fine lenticular opacites on slit-lamp examination - greater than 100 opacities in the equatorial area of both lenses)

2. Prognosis

poor for normal lifestyle
- developmental delays
- visual problems
- progressive mental retardation
with no treatment, patients die in the first decade of complications of Fanconi Syndrome -> chronic renal failure, dehydration, intercurrent infection
extended lifespan with supportive therapy

Pediatric Database - LOWE (OCULO-CEREBRO-RENAL) SYNDROME

Pediatric Organization - Pedbase [at] Gmail.com