Other entities represented in this entry:
ORPHA: 79189, 912; DO: 0080477;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12p13.31 | Peroxisome biogenesis disorder 2A (Zellweger) | 214110 | Autosomal recessive | 3 | PEX5 | 600414 |
A number sign (#) is used with this entry because this form of Zellweger syndrome (PBD2A) is caused by homozygous mutation in the PEX5 gene (600414) on chromosome 12p13.
The peroxisome biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006).
For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100.
Individuals with PBDs of complementation group 2 (CG2) have mutations in the PEX5 gene. For information on the history of PBD complementation groups, see 214100.
Thomas et al. (1975) described a male patient with hyperpipecolic acidemia. Features were persistent hepatomegaly, severe mental retardation, progressive loss of developmental milestones, and diminished visual acuity associated with nystagmus, abnormal discs, and retinal changes. He died at age 2 years following a progressive loss of neurologic function. Pipecolic acid was present in the serum at a concentration of 4 to 5 mg percent and trace amounts were detected in the urine. The complementation studies of Brul et al. (1988) assigned this patient to complementation group 2 (CG2).
Dodt et al. (1995) reported a homozygous mutation in the PEX5 gene in a cell line from a patient with Zellweger syndrome (600414.0002).
Brul, S., Westerveld, A., Strijland, A., Wanders, R. J. A., Schram, A. W., Heymans, H. S. A., Schutgens, R. B. H., van den Bosch, H., Tager, J. M. Genetic heterogeneity in the cerebrohepatorenal (Zellweger) syndrome and other inherited disorders with a generalized impairment of peroxisomal functions: a study using complementation analysis. J. Clin. Invest. 81: 1710-1715, 1988. [PubMed: 2454948] [Full Text: https://doi.org/10.1172/JCI113510]
Dodt, G., Braverman, N., Wong, C., Moser, A., Moser, H. W., Watkins, P., Valle, D., Gould, S. J. Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders. Nature Genet. 9: 115-125, 1995. [PubMed: 7719337] [Full Text: https://doi.org/10.1038/ng0295-115]
Steinberg, S. J., Dodt, G., Raymond, G. V., Braverman, N. E., Moser, A. B., Moser, H. W. Peroxisome biogenesis disorders. Biochim. Biophys. Acta 1763: 1733-1748, 2006. [PubMed: 17055079] [Full Text: https://doi.org/10.1016/j.bbamcr.2006.09.010]
Thomas, G. H., Haslam, R. H. A., Batshaw, M. L., Capute, A. J., Neidengard, L., Ransom, J. L. Hyperpipecolic acidemia associated with hepatomegaly, mental retardation, optic nerve dysplasia and progressive neurological disease. Clin. Genet. 8: 376-382, 1975. [PubMed: 1204235] [Full Text: https://doi.org/10.1111/j.1399-0004.1975.tb01517.x]