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lipid metabolism disorders smith- lemli- opitz syndrome this autosomal recessive disorder of cholesterol biosynthesis is due to deficiency in 7 - dehydrocholesterol reductase . the defect in cholesterol synthesis leads to abnormal development with variable phenotype that can include microcephaly , mental retardation , hypotonia , dysmorphic facies , cleft palate , ambiguous genitalia andcongenital heart disease , plasma cholesterol is reduced ; patients with very low cholesterol levels have a more severe phenotype , and cholesterol deficiency may have a role in dysmorphogenesis , morphological findings include reduced myelination of the cerebral hemispheres and cranial and periphereal nerves , absent corpus callosum, cerebral hypoplasia ,abnormal gyral pattern and altered neuronalmigration . there is pancreatic enlargament and islet cell nuclear hypercromasia and liver has nonspecific changes with cholestasis

conradi - hunnermann syndrome (cdpx2) the x - linked dominant disorder of sterol metabollism is by a deficiency of sterol -beta 8-isomerase that converts 8 - dehydrocholesterol to 7 -dehydrocholesterol, one step before the enzymatic step that is abnormal in smith -lemli opitz syndrome . typical features include chondrodysplasia punctata , bilateral and asymmetrical limb anomalies ,joint contractures , ichthyosiform skin lesions , patchy alopecia , and short stature . the skin lesions are most severe at birth and histologically show hyperkeratosis , parakeratosis , and marked acanthosis , they improve with age , leaving behind follicular atrophoderma ( orangepeel lesions ) and hypopigmented streaks that follow blaschko's lines . it was originally thought that this defect would be lethal in males ; however , there have been two affected males reported ( one of whom was a somatic mosaic for the genetic defect , and the other of whom had a very severe phenotype ) . plasma sterol analysis shows elevated 8 - dehydrocholesterol and 8(9) - cholesterol . bloodcholesterol leves are typically normal


child syndrome (congenital hemidysplasia , ichthyosis and limb defects ). this is another rare x-linked dominant disorder of sterol metabolism characterized by unilateral ichthyosiform skin lesions , often sharply demarcated at the midline of the trunk; limb deficiencies ; and punctate calicifications of the epiphyses and other cartilaginousstructures . in addition , ipsilateral visceral anomalies can be present , including brain ,renal ,lung, and cardiac defects . while some of the skin lesions follow blaschko lines , many patients have more extensive patches of abnormal skin . it is presumed generally lethal males . in most patients , it is caused by a defect in the nsdhl (nad(p)h steroid dehydrogenase - like ) gene , which encodes the 3beta - hydroxysteroid dehydrogenase component of the sterol-4-demethylase protein , one step above the defect for cdpx2 in the cholesterol biosynthesis pathway . a few patients with the child phenotype have been found to have a defect in sterol -beta -8 isomerase as in cdpx2 . the skin abnormality in the nsdhl defect shows marked ichthyosiform epidermal hyperplasia , inflammation , and sometimesfoamy histiocytes within the dermal papillae ( refereed to as verruciform xanthoma) the lesions may regress with age . sterol analysis of plasma , iymphocytes , and fibroblasts shows abnormally increased levels of 4 - methylsterols.
sudden death in infants with inborn erros of metabolism
sudden unexpected death in infancy (SUDI) is defined as sudden unexpected death ocurring before the age of 12months (137). Many metabolic disorders can cuase SUDI or acute metabolic crisis in infants, in some cases without preceding clinical symptoms. Key to the clinical history of a metabolic error presenting in the young infant is deterioration in clinical status after a symptom-free interval of hours to days (29). Findings that may indicate an IEM include family history of a similar sudden death...