Zellweger Syndrome - Cerebrohepatorenal Syndrome

Jason Huston

Dr. Andrew Poznanski

Abstract

Newborn with dysmorphic features, hypotonia, and seizures.

Keywords

1469 Zellweger syndrome Cerebrohepatorenal Peroxisome biogenesis disorder Leukodystrophy


Publication Date: 2008-11-13

History

Newborn initially presented with dysmorphic features, hypotonia, and seizures. The patient then progressed to respiratory failure.

Findings

Image 1: CT head demonstrates an abnormal sulcal gyral pattern predominately anteriorly. These findings are suggestive of poly or pachygyria.

Images 2&3: MR axial and coronal images again demonstrate abnormal gyral pattern with abnormal T2 signal intensity in the subcortical white matter concerning for cortical dysplasia.

Images 4&5: Ultrasound images of the kidneys demonstrate nonspecific increased echogenicity of the kidneys with small cortical cysts.

Image 6: (A different patient)Radiograph of the knee shows extensive punctate calcifications of the patellae.

Image 7: (A different patient) Gross slice of brain shows pachygyria.

Images 8, 9,& 10: (A different patient) Gross and path slide of the kidneys show small subcortical cysts.

Diagnosis

Zellweger Syndrome

DDx

Perosixome Biogenesis Disorders: Infantile Refsum disease, Neonatal adrenal leukodystrophy, hyperpipecolic academia, Zellweger disease

Discussion

Zellweger syndrome, also known as cerebrohepatorenal syndrome, is a autosomal recessive peroxisome biogenesis disorder (PBD). The PBD's fall under the leukodystrophy category. Zellweger is an autosomal recessive disorder and the most severe form of PBD.

The diagnosis of zellweger is a combination of clinical presentation, laboratory, and medical imaging.

Zellweger syndrome involves multiple congenital anomalies.

Craniofacial dysmorphism: high forehead, large anterior fontanelle, hypoplastic supraorbital ridges, broad nasal bridge, micrognathia, deformed ear lobes, redundant nuchal skin folds.

Neurologic abnormalities: psychomotor retardation, profound hypotonia with depressed deep tendon reflexes, seizures, impaired hearing, dysmyelination.

Ocular findings: congenital cataract, glaucoma, retinal degeneration.

Other: liver cirrhosis, jaundice, GI bleeding.

Very long chain fatty acids (VLCFA) are abnormally high in all patients. High iron and copper can be seen in the blood and tissues. Additional labs include erythrocyte plasmalogen, pristanic acid, and phytanic acid.

Imaging modalities include MR, US, and plain radiographs. MR can demonstrate neocortical dysplasia, germinolytic cysts, delayed myelination, and colpocephaly. US will demonstrate cortical cysts and hepatomegaly with or without periportal fibrosis. Radiographs can be used to evaluate respiratory failure and can demonstrate periarticular calcifications which are most pronounced around the patella.

There is no cure or standard course of treatment. Zellweger demonstrates a poor prognosis and death usually occurs by 6 months of age which may be a result of respiratory distress, gastrointestinal bleeding, or liver failure.

References

  1. Chedrawi A, Clark GD. Peroxisomal Disorders. eMedicine. 3 Mar 2007. http://www.emedicine.com/neuro/TOPIC309.HTM
  2. Poznanski AK, Nosanchuk JS, Baublis J, Holt JF. The cerebro-hepato-renal syndrome (CHRS) (Zellweger Syndrome). AJR. 1970;109:313-322.
  3. Mochel F, Grebille AG, et al. Contribution of Fetal MR imaging in the prenatal Diagnosis of Zellweger Syndrome. Am J Neuroradiol. 2007;27:333-336.

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