Ovarian function in Duarte galactosemia

Badik, Jennifer R.; Castañeda, Uriel; Gleason, Tyler J.; Spencer, Jessica B.; Epstein, Michael P.; Fıçıcıoğlu, Can; Fitzgerald, K.; Fridovich‐Keil, Judith L.

doi:10.1016/j.fertnstert.2011.05.088

Cited by 14 publications

(6 citation statements)

References 24 publications

(37 reference statements)

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“…Potential explanations for the disparity include the limited size of the Powell et al 6 cohort and the possibility that the difference in receipt of special services detected by Powell et al 6 reflected a difference in access to services rather than a difference in the actual prevalence of speech and language difficulties. Of note, although we did not test ovarian function in this study, researchers in a previous study 8 reported no significant difference in anti-Mullerian hormone or folliclestimulating hormone levels between 57 girls with DG and 64 controls, effectively demonstrating that girls with DG, unlike their counterparts with CG, are not at high risk for premature ovarian insufficiency.…”

Section: Discussionmentioning

confidence: 66%

Developmental Outcomes in Duarte Galactosemia

Carlock¹,

Fischer²,

Lynch

et al. 2019

Pediatrics

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OBJECTIVES: For decades, infants with Duarte galactosemia (DG) have been identified by newborn screening (NBS), but whether they should be treated with dietary restrictions of galactose has remained unknown. To clarify, we conducted a study of dietary and developmental outcomes in 206 children with DG (case patients) and 144 controls, all of whom were 6 to 12 years old. METHODS:We recruited case patients from states where they were identified by NBS; unaffected siblings served as controls. Diet in infancy was ascertained by retrospective parent surveys; developmental outcomes were assessed in 5 domains, yielding 73 outcome measures for each child. We divided subjects randomly into independent discovery (n = 87) and validation (n = 263) sets. We tested the discovery set to order the 73 outcome measures by ascending P values and tested the 10 outcomes with the lowest P values for possible association with DG in the validation set. We also tested these same 10 outcomes for possible association with milk exposure in infancy among case patients in the validation set. RESULTS:None of the 73 outcomes tested in the discovery set revealed significant association with DG, and none of the 10 outcomes tested in the validation set revealed either significant association with DG or significant association with milk exposure among children with DG. CONCLUSIONS:Through our results, we demonstrated that there were no significant differences in outcomes tested between case patients and controls or among case patients as a function of milk exposure in infancy. In this study, we provide a long-needed foundation of knowledge for health care providers, families, and NBS professionals seeking to make evidence-based decisions about DG.

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Section: Discussionmentioning

confidence: 66%

Developmental Outcomes in Duarte Galactosemia

Carlock¹,

Fischer²,

Lynch

et al. 2019

Pediatrics

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“…Later Waggoner et al (1990) reported that 17% (8/47) galactosemic women presented with ovarian failure. However, with regard to duarte galactosemia, a mild variant of GALT deficiency, no apparent ovarian dysfunction was reported ( Badik et al , 2011 ). Pathogenesis involves excess galactose toxicity that impairs folliculogenesis, induces resistance to gonadotrophins and accelerates follicular atresia ( Fridovich-Keil et al , 2011 ; Banerjee et al , 2012 ).…”

Section: Resultsmentioning

confidence: 99%

Genetics of primary ovarian insufficiency: new developments and opportunities

Qin

Jin

Simpson

et al. 2015

Hum. Reprod. Update

397

336

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BACKGROUNDPrimary ovarian insufficiency (POI) is characterized by marked heterogeneity, but with a significant genetic contribution. Identifying exact causative genes has been challenging, with many discoveries not replicated. It is timely to take stock of the field, outlining the progress made, framing the controversies and anticipating future directions in elucidating the genetics of POI.METHODSA search for original articles published up to May 2015 was performed using PubMed and Google Scholar, identifying studies on the genetic etiology of POI. Studies were included if chromosomal analysis, candidate gene screening and a genome-wide study were conducted. Articles identified were restricted to English language full-text papers.RESULTSChromosomal abnormalities have long been recognized as a frequent cause of POI, with a currently estimated prevalence of 10–13%. Using the traditional karyotype methodology, monosomy X, mosaicism, X chromosome deletions and rearrangements, X-autosome translocations, and isochromosomes have been detected. Based on candidate gene studies, single gene perturbations unequivocally having a deleterious effect in at least one population include Bone morphogenetic protein 15 (BMP15), Progesterone receptor membrane component 1 (PGRMC1), and Fragile X mental retardation 1 (FMR1) premutation on the X chromosome; Growth differentiation factor 9 (GDF9), Folliculogenesis specific bHLH transcription factor (FIGLA), Newborn ovary homeobox gene (NOBOX), Nuclear receptor subfamily 5, group A, member 1 (NR5A1) and Nanos homolog 3 (NANOS3) seem likely as well, but mostly being found in no more than 1–2% of a single population studied. Whole genome approaches have utilized genome-wide association studies (GWAS) to reveal loci not predicted on the basis of a candidate gene, but it remains difficult to locate causative genes and susceptible loci were not always replicated. Cytogenomic methods (array CGH) have identified other regions of interest but studies have not shown consistent results, the resolution of arrays has varied and replication is uncommon. Whole-exome sequencing in non-syndromic POI kindreds has only recently begun, revealing mutations in the Stromal antigen 3 (STAG3), Synaptonemal complex central element 1 (SYCE1), minichromosome maintenance complex component 8 and 9 (MCM8, MCM9) and ATP-dependent DNA helicase homolog (HFM1) genes. Given the slow progress in candidate-gene analysis and relatively small sample sizes available for GWAS, family-based whole exome and whole genome sequencing appear to be the most promising approaches for detecting potential genes responsible for POI.CONCLUSIONTaken together, the cytogenetic, cytogenomic (array CGH) and exome sequencing approaches have revealed a genetic causation in ∼20–25% of POI cases. Uncovering the remainder of the causative genes will be facilitated not only by whole genome approaches involving larger cohorts in multiple populations but also incorporating environmental exposures and exploring signaling pathways in intragenic and interge...

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“…Hence, the counseling of the patient with classic galactosemia and her family about the chances of pregnancy is complicated. Interestingly, limited evidence suggests that girls and women with Duarte variant galactosemia are not at increased risk for POI [82].…”

Section: Clinical Presentation and Coursementioning

confidence: 99%

Primary ovarian insufficiency in classic galactosemia: current understanding and future research opportunities

Thakur

Feldman

Puscheck

2017

J Assist Reprod Genet

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Classic galactosemia is an inborn error of the metabolism with devastating consequences. Newborn screening has been successful in markedly reducing the acute neonatal symptoms from this disorder. The dramatic response to dietary treatment is one of the major success stories of newborn screening. However, as children with galactosemia achieve adulthood, they face long-term complications. A majority of women with classic galactosemia develop primary ovarian insufficiency and resulting morbidity. The underlying pathophysiology of this complication is not clear. This review focuses on the reproductive issues seen in girls and women with classic galactosemia. Literature on the effects of classic galactosemia on the female reproductive system was reviewed by an extensive Pubmed search (publications from January 1975 to January 2017) using the keywords: galactosemia, ovarian function/dysfunction, primary ovarian insufficiency/failure, FSH, oxidative stress, fertility preservation. In addition, articles cited in the search articles and literature known to the authors was also included in the review. Our understanding of the role of galactose metabolism in the ovary is limited and the pathogenic mechanisms involved in causing primary ovarian insufficiency are unclear. The relative rarity of galactosemia makes it difficult to accumulate data to determine factors defining timing of ovarian dysfunction or treatment/fertility preservation options for this group of women. In this review, we present reproductive challenges faced by women with classic galactosemia, highlight the gaps in our understanding of mechanisms leading to primary ovarian insufficiency in this population, discuss new advances in fertility preservation options, and recommend collaboration between reproductive medicine and metabolic specialists to improve fertility in these women.

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Ovarian function in Duarte galactosemia

Cited by 14 publications

References 24 publications

Developmental Outcomes in Duarte Galactosemia

Developmental Outcomes in Duarte Galactosemia

Genetics of primary ovarian insufficiency: new developments and opportunities

Primary ovarian insufficiency in classic galactosemia: current understanding and future research opportunities

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