Clinical approach to inherited peroxisomal disorders.

[neonatal adrenoleukodystrophy]

At least 21 genetic disorders have now been found that are linked to peroxisomal dysfunction . Whatever the genetic defect might be , peroxisomal disorders should be considered in various clinical conditions , dependent on the age of onset . The prototype of peroxisomal disorders is represented by 'classical ' Zellweger syndrome (ZS ) which is the most severe disorder combining all the characteristic symptoms . ZS is characterized by the association of errors of morphogenesis , severe neurological dysfunction , neurosensory defects , regressive changes , hepatodigestive involvement with failure to thrive , usually early death , and absence of recognizable liver peroxisomes . Other peroxisomal disorders (pseudo-Zellweger syndrome , neonatal adrenoleukodystrophy (NALD ), pseudo-neonatal adrenoleukodystrophy , rhizomelic chondrodysplasia punctata (RCDP ), and hyperpipecolic acidaemia ) share some of these symptoms , but with varying organ involvement , severity of dysfunction , and duration of survival . The diagnosis should not cause difficulty when all the characteristic manifestations are present . Depending on the main presenting sign , peroxisomal disorders in neonates should be suspected in two categories of circumstances : polymalformative syndrome with craniofacial dysmorphism , and severe neurological dysfunction . During the first 6 months of life , the predominant symptoms may be hepatomegaly , prolonged jaundice , liver failure , anorexia , vomiting and diarrhoea leading to failure to thrive resembling a malabsorption syndrome ; severe psychomotor retardation , hearing loss and ocular abnormalities become evident . Beyond 4 years of age , behavioural changes , intellectual deterioration , visual impairment and gait abnormalities may be the presenting symptoms . Independently of the clinical symptoms and age of onset , most peroxisomal disorders described so far can be clinically screened by recordings of electroretinogram , visual -evoked responses , and brain auditory-evoked responses , which are almost always abnormal . Nine of the 17 peroxisomal disorders with neurological involvement are associated with an accumulation of very long -chain fatty acids (VLCFA ), which suggests that assay of plasma VLCFA should be used as a primary test . However , assays of plasma phytanic acid and plasma /urine bile acid intermediates should also be performed in view of the recent reports of atypical chondrodysplasia variants (without rhizomelic shortening ) and isolated trihydroxycholestanoic aciduria . The differential diagnoses in various clinical conditions and age periods are discussed .

Diseases
Validation

Diseases presenting "prolonged jaundice" symptom

benign recurrent intrahepatic cholestasis

neonatal adrenoleukodystrophy

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