Vitamin A deficiency in an infant with PAGOD syndrome

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 inhuman 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.

Original languageEnglish (US)
Pages (from-to)2241-2247
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume149
Issue number10
DOIs
StatePublished - Oct 2009

Fingerprint

Vitamin A Deficiency
Tretinoin
Vitamin A
Mothers
Nucleic Acid Hybridization
Umbilical Hernia
Retinol-Binding Proteins
Endoderm
Mutation
Retinoic Acid Receptors
Hypogonadism
Karyotype
Placenta
Pulmonary Artery
Embryonic Development
Testis
Animal Models
Chromosomes
Phenotype
Pregnancy

Keywords

  • Agonadism
  • Dextrocardia
  • Omphalocele/diaphragmatic defect
  • Pulmonary hypoplasia
  • Vitamin A deficiency

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Vitamin A deficiency in an infant with PAGOD syndrome. / Gavrilova, Ralitza M; Babovic, Nikola; Lteif, Aida; Eidem, Benjamin W.; Kirmani, Salman; Olson, Timothy Mark; Babovic-Vuksanovic, Dusica.

In: American Journal of Medical Genetics, Part A, Vol. 149, No. 10, 10.2009, p. 2241-2247.

Research output: Contribution to journalArticle

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