PEX1

Peroxisome Biogenesis Disorder 3B (Infantile Refsum Disease)

Clinical Characteristics
Ocular Features: 

This peroxisomal disorder presents in the first year of life with both systemic and ocular features.  Night blindness is the major ocular feature and at least some have optic atrophy similar to the adult form.  Nystagmus may be present.  Reduction or absence of rod responses on ERG can be used in young children to document the retinopathy. Blindness and deafness commonly occur in childhood.

Systemic Features: 

This disorder is classified as a peroxisomal biogenesis disorder (PBD) associated with the breakdown of phytanic acid.  Ataxia and features of motor neuron disease are evident early.  Hepatomegaly and jaundice may also be an early diagnostic feature as bile acid metabolism is defective.  Infant hypotonia is often seen.  Nonspecific facial dysmorphism has been reported as a feature. The teeth are abnormally large and often have yellowish discoloration.  Postural unsteadiness is evident when patients begin walking.  Diagnosis can be suspected from elevated serum phytanic and pipecolic acid (in 20% of patients) or by demonstration of decreased phytanic acid oxidation in cultured fibroblasts.  Other biochemical abnormalities such as hypocholesterolemia and elevated very long chain fatty acids and trihydroxycholestanoic acid are usually present.  Anosmia and mental retardation are nearly universal features.  Early mortality in infancy or childhood is common although some survive into the 2nd and 3rd decades.

Genetics

This is an autosomal recessive peroxisomal biogenesis disorder (PBD) resulting from mutations in a number of PEX genes (PEX1, PEX2, PEX3, PEX12, PEX26).  It shares many features with other PBDs including those formerly called Zellweger syndrome (214100), rhizomelic chondrodysplasia punctata (215100), and neonatal adrenoleukodystrophy (601539).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment is known.

References
Article Title: 

Adrenoleukodystrophy, Autosomal

Clinical Characteristics
Ocular Features: 

This early onset and rapidly progressive form of adrenoleukodystrophy is rare.  The early onset and rapidly fatal course of the disease has limited full delineation of the ocular features.  The most striking is the presence of 'leopard-spots' pigmentary changes in the retina.  Polar cataracts, strabismus, and epicanthal folds have also been reported. 

Systemic Features: 

Onset of symptoms occurs shortly after birth often with seizures and evidence of psychomotor deficits.  Rapid neurologic deterioration begins at about 1 year of age with death usually by the age of 3 years.  Hyperpigmentation of the skin may be apparent a few months after birth.  Opisthotonus has been observed.  The ears may be low-set, the palate is highly arched, and the nostrils anteverted.  Frontal bossing may be present.  Serum pipecolic acid and very-long-chain fatty acids (VLCFAs) can be markedly elevated.  Cystic changes in the kidneys have been reported. 

Genetics

This is an autosomal recessive peroxismal disorder resulting from homozygous mutations in receptor gene mutations such as PEX1, PEX5, PEX13, and PEX26.

There is also an X-linked recessive adrenoleukodystrophy (300100) sometimes called ALD but it lacks some of the morphologic features and is somewhat less aggressive. 

Neonatal adrenoleukodystrophy along with infantile Refsum disease (266510, 601539) and Zellweger syndrome (214100) are now classified as Zellweger spectrum or perioxismal biogenesis disorders.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Treatment is mainly supportive for associated health problems. 

References
Article Title: 

Peroxisome Biogenesis Disorder 1B (neonatal adrenoleukodystrophy)

Clinical Characteristics
Ocular Features: 

This peroxisomal disorder presents in the first year of life with both systemic and ocular features.  Night blindness is the major ocular feature and at least some have optic atrophy similar to the adult form.  Central acuity is reduced secondary to macular degeneration.  A pigmentary retinopathy is frequently present and often follows the appearance of whitish retinal flecks in the midperipheray.  Nystagmus and cataracts are common features.  Reduction or absence of ERG responses can be used in young children to document the retinopathy.  Blindness and deafness commonly occur in childhood.

Systemic Features: 

This disorder is classified as a leukodystrophy, or disease of white matter of the brain, associated with the breakdown of phytanic acid.  Ataxia and features of motor neuron disease are evident early.  Hepatomegaly and jaundice may also be early diagnostic features as bile acid metabolism is defective.  Infant hypotonia is often seen.  Nonspecific facial dysmorphism has been reported.  The ears are low-set and epicanthal folds are present.  The teeth are abnormally large and often have yellowish discoloration.  Postural unsteadiness is evident when patients begin walking.  Diagnosis can be suspected from elevated serum phytanic and pipecolic acid (in 20% of patients) or by demonstration of decreased phytanic acid oxidation in cultured fibroblasts.  Other biochemical abnormalities such as hypocholesterolemia, and elevated very long chain fatty acids and trihydroxycholestanoic acid are usually present.  Anosmia, developmental delays, and mental retardation are nearly universal features.  Early mortality in infancy or childhood is common.

Genetics

This is a genetically heterogeneous disorder of peroxisome biogenesis caused by mutations in at least three genes, PEX1 (7q21-q22), PEX2 (8q21.1), and PEX6 (22q11-21).  Each is inherited in an autosomal recessive pattern.  The mechanism of disease is different from the classic or adult Refsum disorder (266500) and some have debated whether the term ‘infantile Refsum disease’ is appropriate.

This disorder shares some clinical features with other peroxisomal disorders such as Zellweger syndrome (214100) and rhizomelic chondrodysplasia punctata (215100).  Zellweger syndrome (214100), neonatal adrenoleukodystrophy and infantile Refsum disease (601539) are now considered to be peroxisomal biogenesis or Zellweger spectrum disorders.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No effective treatment is known.

References
Article Title: 
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