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At a Glance

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A disorder characterized by the congenital absence of functioning peroxisomes (the cellular structures that are responsible for the elimination of toxic substances) resulting in a cerebrohepatorenal syndrome. The disease affects brain development, particularly nerve myelination. Most important features include hepatomegaly, polycystic kidney disease, visual disturbances, and high plasma levels of iron and copper. Other clinical features include muscular hypotonia already noticeable at birth, mental retardation, seizures, coagulopathy, and dysphagia with recurrent aspiration. Congenital heart defects have been described. Life expectancy is approximately 6 months.

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Synonym

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Cerebro-Hepato-Renal Syndrome.

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Genetic Inheritance

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Autosomal recessive. Gender distribution is equal. Gene map locus is at 7q11.23. There are several phenotypes that are caused by mutations in any of the several different genes involved in peroxisome biogenesis.

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Pathophysiology

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Thought to be a group of disorders of peroxisomal biogenesis in which the primary defect involves the import mechanisms of matrix enzymes. This results in production of “ghost” organelles that consist of an empty membrane.

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Diagnosis

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Clinically evocated by aberrant development of the skull, face, ears, eyes, hands, and feet, polycystic kidneys, and intrahepatic biliary dysgenesis. Confirmed by biochemical studies involving blood cells and fibroblasts. The presence of high levels of iron and copper in the blood is characteristic of this disease. There are specific and sensitive biochemical assays of peroxisomal function available, including a decreased dihydroxyacetone phosphate-adenosine triphosphate (DHAP-AT) activity and an increase in very-long-chain fatty acids. Serum iron and iron-binding capacity are high and peroxisomes are abnormal.

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Clinical Aspects

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These infants are subject to early death within a few months (mean = 12.5 weeks). The clinical features involve head (high forehead, flat facies, cleft palate, micrognathia, characteristic eye changes, including mongoloid slant, hypertelorism, Brushfield spots, cataracts, pigmentary retinopathy, and optic nerve dysplasia) and central nervous system (CNS) (seizures, absent Moro reflex). Prenatal growth failure, failure to thrive, poor suck, muscular hypotonia, mental retardation, areflexia, deafness and congenital heart defects (patent ductus arteriosus, septal defects, aortic abnormalities) can be observed. Others features include apneas, polycystic kidneys, cryptorchidism, hepatomegaly, jaundice, mitochondrial abnormalities, liver cirrhosis, camptodactyly, talipes equinovarus, and stippled chondral calcification.

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Precautions before Anesthesia

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Full assessment of the disorder and the extent of involvement of neurological, cardiac, respiratory, and hepatic systems. It is recommended to obtain consultation with appropriate specialties, and investigations. Because preoperative fasting is not tolerated by the infant, an endocrine consultation may be required to discuss appropriate intravenous fluids and supplementation. Complete assessment of coagulation. Correct hypoprothrombinemia.

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Anesthetic Considerations

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The usually severe neurological problems may require the insertion of a gastrostomy tube for palliative feeding, which can often be achieved with an eutectic mixture of local anesthetics and infiltration of local anesthesia. The presence ...

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