PEDBASE.org - The Pediatric Database - Detailed information of ZELLWEGER'S SYNDROME

ZELLWEGER'S SYNDROME

DEFINITION:

A disorder of peroxisomes characterized by the congenital absence of functioning peroxisomes resulting in a cerebrohepatorenal syndrome.

EPIDEMIOLOGY:

incidence: rare
age of onset:
- newborn
risk factors:
- familial - autosomal recessive
  - chrom. #: 7q11.23
  - gene: ?
- M = F

PATHOGENESIS:

1. Group 1 Peroxisomal Disorders

thought to be a group of disorders of peroxisome biogenesis where the primary defect involves the import mechanisms of matrix enzymes
the peroxisomes in these disorders are not entirely absent but consist of empty membrane "ghosts" (these membranes contain the 3 integral membrane proteins specific to peroxisomes)
this results in abnormalities of peroxisomal function secondary to the failure of multiple peroxisomal enzymes:

1. Anabolic Dysfunction

decreased plasmalogen
increased bile acid intermediates

2. Catabolic Dysfunction

increased catalase (in the cytosol)
increased VLCFA
increased phytanic acid
increased L-pipecolic acid

2. History

Bowen et al., (1964)
- first to describe Zellweger's Syndrome
Goldfischer et al., (1973)
- first to establish a connection between the absence of peroxisomes and Zellwegner's Syndrome

CLINICAL FEATURES:

1. Typical Facies

epicanthal folds
high forehead
hypoplastic supraorital ridges
upslanting palpebral fissures

2. Neurologic Manifestations

severe infantile hypotonia
neonatal seizures
limited psychomotor development

3. Ophthalmologic Manifestations

corneal clouding
Brushfield spots
cataracts
glaucoma
optic nerve dysplasia
pigmentary retinopathy

4. Cardiovascular Manifestations

VSD (32%)
aortic anomalies (22%)

5. Gastrointestional Manifestations

cholestasis +/- fat malabsorption due to paucity of the intrahepatic bile ducts
hepatomegaly

INVESTIGATIONS:

1. Diagnostic (Biopsy)

the presence of peroxisomal "ghosts" in the liver, kidney, and cultured skin fibroblasts

2. Pathology

1. Central Nervous System

striking & characteristic disorder of neuronal cell migration involving the cerebral hemispheres, cerebellum, and inferior olivary nucleus

2. Liver

enlarged (78%), fibrotic (76%), micronodular cirrhosis (37%)
excessive iron deposits early

3. Renal

cysts (78%) - vary from glomerular microcysts to large cortical cysts of glomerular and tubular origin

4. Adrenal Gland

cytoplasmic lamellar inclusions

3. Imaging Studies

1. Skeletal X-Rays

calcific stippling of the patella and acetabular synchrondosis (50%)

2. CT/MRI

agenesis of the corpus callosum

MANAGEMENT:

1. Classic Zellweger syndrome

1. Supportive

no treatment for underlying disorder
multidisciplinary approach
- Paediatrics, Neurology, Ophthalmology, Cardiology, etc
- genetic counselling

2. Prognosis

rarely live more than a few months (mean = 12.5 weeks)

2. Milder Forms

1. Supportive

multidisciplinary early intervention
oral administration of plasmalogens
restricted phytanic acid intake
OT, PT, hearing aids, nutrition

Pediatric Database - ZELLWEGER'S SYNDROME

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