How to cite this article: Gavrilova R, Babovic N, Lteif A, Eidem B, Kirmani S, Olson T, Babovic-Vuksanovic D. 2009. Vitamin A deficiency in an infant with PAGOD syndrome. Am J Med Genet Part A 149A:2241–2247.
Vitamin A deficiency in an infant with PAGOD syndrome†
Article first published online: 16 SEP 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 10, pages 2241–2247, October 2009
How to Cite
Gavrilova, R., Babovic, N., Lteif, A., Eidem, B., Kirmani, S., Olson, T. and Babovic-Vuksanovic, D. (2009), Vitamin A deficiency in an infant with PAGOD syndrome. Am. J. Med. Genet., 149A: 2241–2247. doi: 10.1002/ajmg.a.32998
- Issue published online: 24 SEP 2009
- Article first published online: 16 SEP 2009
- Manuscript Accepted: 3 JUN 2009
- Manuscript Received: 14 AUG 2008
- vitamin A deficiency;
- pulmonary hypoplasia;
- omphalocele/diaphragmatic defect
PAGOD syndrome is a rare condition characterized by multiple congenital anomalies including pulmonary artery and lung hypoplasia, agonadism, diaphragmatic abnormalities, cardiac defects, omphalocele, and various genital anomalies. The etiology of this condition is unknown but the spectrum of birth defects is similar to the developmental anomalies observed in vitamin A deficiency animal models. We describe an infant with PAGOD syndrome phenotype. The patient had a normal male karyotype and no copy number changes were seen on chromosome genomic hybridization (CGH) microarray. Endocrine evaluation was consistent with primary hypogonadism. The testes and Müllerian structures were absent by imaging studies, raising the possibility of arrest of early gonadogenesis. The plasma free vitamin A was low, consistent with moderate to severe vitamin A deficiency; the maternal plasma vitamin A level was normal. During pregnancy maternal vitamin A is taken up by retinol binding protein 4 (RBP4) which is expressed in the embryonic visceral endoderm from pregastrulational stages. This transport is mediated via the specific membrane receptor for RBP, stimulated by retinoic acid 6 (STRA6). STRA6 is widely expressed in human organ systems including the placenta during embryonic development. Mutations in the STRA6 gene result in Matthew–Wood syndrome, which demonstrates significant phenotypic overlap with PAGOD syndrome. Sequencing of STRA6 coding regions in our patient, revealed no mutations. We present a case of PAGOD syndrome with a review of the literature, posing the hypothesis that a vitamin A metabolic defect, other than transport mediated by STRA6 receptor, might have an etiological role in the development of this multiple congenital anomalies syndrome. © 2009 Wiley-Liss, Inc.