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.
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
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.
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.
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.
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.
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 of muscular hypotonia must be
considered. Ketamine is a useful supplement
when general anesthesia
not recommended. If anesthesia must be given, considerations include the
possibility of a difficult intubation, poor protection of the airway and
recurrent pulmonary aspiration, tendency to apnea postoperatively, and
complicating factors such as ...