Most severe manifestation of disease within the spectrum of peroxisome biogenesis disorders. 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 noticeable at birth, mental retardation, seizures, coagulopathy, and dysphagia with recurrent aspiration. Life expectancy is approximately 6 months but may reach infancy or late childhood in milder forms.
Autosomal recessive. Gender distribution is equal. Estimated worldwide prevalence between 1:50,000 and 1:100,000. Disease-associated mutations have been identified in 13 of 16 peroxin or PEX genes with PEX1 (two-thirds of cases) and PEX5 and PEX6 the most common mutations in a Middle East cohort. Mutation results in reduced or nonfunctioning peroxin essential in peroxisome biogenesis.
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. Incomplete peroxisomes fail to beta oxidize fatty acids with a chain length of more than 22 carbons and similar compounds resulting in an intracellular accumulation of very long chain fatty acids (VLCFA) and reduced plasmalogen synthesis affecting developing organs.
Clinically evocated by aberrant development of the skull, face, ears, eyes, hands, and feet, polycystic kidneys, and intrahepatic biliary dysgenesis. Screening test for an infant with suspected Zellweger Syndrome is a measurement of plasma VLCFA concentrations. Elevated plasma concentrations of specific VLCFA (hexacosanoic and tetracosenoic acid) are consistent with peroxisomal disease. Other biochemical tests identify a decreased dihydroxyacetone phosphate-adenosine triphosphate (DHAP-AT) activity and plasmalogen concentrations.
The most severe forms are subject to an 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.
Precautions before anesthesia
Full assessment of the disorder and the extent of involvement of neurological, cardiac, respiratory, hepatic, and renal systems. Preoperative fasting is poorly tolerated by the infant and an endocrine consultation may be required to discuss appropriate intravenous fluids and supplementation. Complete assessment of coagulation. Correct hypoprothrombinemia.
The usually severe neurological problems may require the insertion of a gastrostomy ...