Peroxisomal disorders neonatal

Peroxisomal disorders (Zellweger syndrome, Refsum s disease, neonatal adre-noleukodystrophy) are characterised by defective peroxisome biogenesis, or, being present, peroxisomes lacking / -oxidative enzymes. In the BA biosynthetic pathway, dihydroxycoprostanic acid (DHCA) and trihydroxycoprostanic acid (THCA) are /1-oxidised in peroxisomes to produce CA and CDCA, respectively, whereas peroxisomal disorders cause a defective oxidation of the BA precursor side chain, which leads to an accumulation of C27 bile acids, notably 3 ,7 -dihydroxy-5/3-cholesta-noic acid (DHCA) and 3a,7a,12a-trihydroxy-5/l-cholestanoic acid (THCA), in the plasma and urine of affected patients. 

The elevation of VLCFA can be detected in most body tissues and fluids and forms the basis for a diagnostic assay for the identification of affected individuals.The most frequently used test is the measurement of VLCFA in plasma which has been shown to be very sensitive. Although VLCFA are increased in some of the other peroxisomal disorders, including Zellweger syndrome, infantile Refsum disease, and neonatal ALD, the clinical presentations of these disorders are very different from X-ALD, and the discrimination of... 

Specific defects in bile acid synthesis Cerebrotendinous xanthomatosis Intrahepatic cholestasis familial neonatal hepatitis) 3-p-hydroxysteroid dehydrogenase/isomerase deficiency A -3-oxosteroid 5-P-reductase deficiency C24 steroid 7-a-hydroxylase deficiency Peroxisomal disorders... 

In addition to primary defects in bUe acid synthesis, secondary abnormalities have been noted in peroxisomal disorders, such as neonatal adrenoleukodystrophy and cerebrohepatorenal (ZeUweger s) syndrome—an autosomal recessive condition associated with severe cholestasis in which side chain oxidation is impaired. 

Vanhole, C., F. de Zegher, P. Casaer, H. Devlieger, R. J. Wanders, G. Vanhove, and J. Jaeken. 1994. A new peroxisomal disorder with fetal and neonatal adrenal insufficiency. Arch Dis Child Fetal Neonatal Ed 71 F55-56. 

Poll-The BT, Roels F, Ogier H, Scotto J, Vamecq J, Schiitgens RBH et al. A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy). Am J Hum Genet 1988 42(3) 422-434. 

Diagnosis of the 4 inborn errors of bile acid synthesis discussed in this chapter is important because three are treatable by oral bile acid supplementation (such treatment was not successful in the single reported case of oxysterol 7a-hydroxylase deficiency). Liquid secondary ion mass spectrometry (LSI-MS) is a simple and rapid method which can be used to screen urine samples for abnormal cholanoids (bile acids and bile alchohols). It should be applied to neonates with unexplained cholestatic liver disease, particularly if familial and associated with steatorrhoea and fat-soluble vitamin malabsorption, to infants and children with developmental delay whether or not this is associated with specific features suggestive of a peroxisomal disorder (e.g. hypotonia, seizures, dysmorphic features, ocular and auditory abnormalities and hepatic dysfunction) or CTX (e.g. juvenile cataracts). 

Fatal hereditary disorder that typically presents in the neonatal period. Clinical features include an array of hepatic, renal and neurological dysfunctions. Patients with Zellweger syndrome rarely survive the first year of life. The disease is caused by mutations in the Pex proteins leading to an defective import of peroxisomal matrix proteins and consequently to a loss of most peroxisomal metabolic pathways. 

Three genetic disorders Zellweger s syndrome, neonatal adrenoleukodystrophy, and childhood adrenoleukodys-trophy) exhibit defective formation of peroxisomes (in Zellweger s syndrome no morphologically detectable peroxisomes are present) or deficiency of one or more constituent enzymes. All three disorders are characterized by a marked accumulation of very long chain, saturated, unbranched fatty acids (tetracosanoic and hexacosanoic acids) in liver and central nervous system tissues, severe neurological symptoms, and early death. 

D-bifunctional protein deficiency (D-BP), the second peroxisomal -oxidation disorder, was only delineated recently [6-9]. All patients identified sofar (>40 see [10]) show severe clinical abnormalities including hypotonia, craniofacial dysmorphia, neonatal seizures, hepatomegaly, and developmental delay. Most patients with D-BP deficiency die in the first year of life. A remarkable observation is that patients with D-BP deficiency show disordered neuronal migration as in ZS. 

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