Hypergonadotropic Hypogonadism in Female Patients with Galactosemia

Kaufman, Francine; Kogut, Maurice D.; Donnell, George N.; Goebelsmann, Uwe; March, Charles M.; Koch, Richard

doi:10.1097/00006254-198109000-00018

Cited by 33 publications

(51 citation statements)

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“…often observed in ~a t i e n t s with galactosemia, is due to interference with nucleotide sugar metabolism and the synthesis of galactose containing glycoproteins and glycolipids consequent to the enzymatic defect in the major pathway of galactose metabolism. (Pediatr Res 25:151-155,1989) Abbreviations transferase, galactose-1-phosphate uridyl transferase epimerase, uridine diphosphogalactose-4-epimerase G6PD, glucose-6-phosphate dehydrogenase PGM, phosphoglucomutase TCA, trichloroacetic acid UDPGlc, uridine diphosphoglucose UDPGal, uridine diphosphogalactose UTP, uridine triphosphate treatment is begun in early infancy (1). The clinical symptoms of gonadal insufficiency have included partial or complete failure of secondary sexual development, primary amenorrhea, the postpubertal occurrence of oligomenorrhea, and secondary amenorrhea.…”

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confidence: 99%

“…Although streak ovaries have been observed in two patients (2,3), the pathophysiology of the ovarian insult is unknown. It has been hypothesized that metabolites of galactose, particularly galactose-I-phosphate, may be toxic to the ovarian parenchyma during the prenatal state (4) or the perinatal period (1). The exact mechanism of this toxicity, however, has not been elucidated.…”

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Galactose Metabolism in Human Ovarian Tissue

Ng²,

Kaufman

et al. 1989

Pediatr Res

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ABSTRACT. Galactose metabolism was studied in human ovarian tissue obtained from 14 women controls between 21 and 72 y of age, and one 21-y-old galactosemic patient with hypergonadotrophic hypogonadism. Tissue slices were incubated with l-'4C-galactose, and labeled intermediates were analyzed by anion-exchange column chromatography. Activities of enzymes related to the galactose pathway: galactokinase, transferase, epimerase, uridine diphosphoglucose (UDPGlc) and uridine diphosphogalactose pyrophosphorylases, and UDPGlc and uridine diphosphogalactose pyrophosphatases were measured in ovarian homogenates using radioisotopic, spectrophotometric, and fluorometric techniques. Incorporation of carbon label from l-'4C-galactose into various galactose and glycolytic intermediates, as well as carbon dioxide and TCA-insoluble materials was demonstrated in samples from non-galactosemic controls. In tissue from the galactosemic individual, no labeled carbon dioxide was produced and very little incorporation into TCA-insoluble material was found. Labeled galactose-1-phosphate was elevated. In normal ovarian tissue, specific activities of galactokinase, transferase, epimerase, and UDPGlc pyrophosphorylase are much higher than those found in the red cells and in testes. UDPGlc pyrophosphorylase activity is about 50 times that of transferase, suggesting that uridine nucleotide sugars have an important role in the normal development and function of the ovary. It is hypothesized that premature ovarian failure. often observed in ~a t i e n t s with galactosemia, is due to interference with nucleotide sugar metabolism and the synthesis of galactose containing glycoproteins and glycolipids consequent to the enzymatic defect in the major pathway of galactose metabolism. (Pediatr Res 25:151-155,1989) Abbreviations transferase, galactose-1-phosphate uridyl transferase epimerase, uridine diphosphogalactose-4-epimerase G6PD, glucose-6-phosphate dehydrogenase PGM, phosphoglucomutase TCA, trichloroacetic acid UDPGlc, uridine diphosphoglucose UDPGal, uridine diphosphogalactose UTP, uridine triphosphate treatment is begun in early infancy (1). The clinical symptoms of gonadal insufficiency have included partial or complete failure of secondary sexual development, primary amenorrhea, the postpubertal occurrence of oligomenorrhea, and secondary amenorrhea. Although streak ovaries have been observed in two patients (2, 3), the pathophysiology of the ovarian insult is unknown. It has been hypothesized that metabolites of galactose, particularly galactose-I-phosphate, may be toxic to the ovarian parenchyma during the prenatal state (4) or the perinatal period (1). The exact mechanism of this toxicity, however, has not been elucidated.To gain a better understanding of galactose metabolism in the normal human ovary, galactose oxidation and its by-products were studied in ovarian tissue slices. In addition, the enzymes involved in the metabolic process were assayed, including galactokinase, galactose-1 -phosphate uridyl transferase, UDPGal-4-ep...

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confidence: 99%

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confidence: 99%

Galactose Metabolism in Human Ovarian Tissue

Ng²,

Kaufman

et al. 1989

Pediatr Res

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“…Severe phenotypes lead to lethal toxic syndrome and cognitive and motor abnormalities [75]. 17%-67% galactosemic women are reported to have POI [71,76], and studies show that classic galactosaemia leads to varied level of ovarian dysfunction in different individuals [77]. Almost all women with homozygous mutation in the GALT gene present POI sooner or later in their lives [71].…”

Section: Metabolic Disordersmentioning

confidence: 99%

An update on primary ovarian insufficiency

Jin

Huang

2012

Sci. China Life Sci.

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Primary ovarian insufficiency (POI) occurs in about 1% of female population under the age of 40, leading to reproductive problems, an earlier encounter with menopausal symptoms, and complicated diseases. There are three presumable mechanisms involved in the development of POI, namely apoptosis acceleration, follicular maturation blocking and premature follicle activation, through the following studied causes: (i) chromosomal abnormalities or gene mutations: mostly involve X chromosome, such as FMR1 premutation; more and more potentially causal genes have been screened recently; (ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency; (iii) autoimmune mediated ovarian damage: observed alone or with some certain autoimmune disorders and syndromes; but the specificity and sensitivity of antibodies towards ovary are still questionable; (iv) iatrogenic: radiotherapy or chemotherapy used in cancer treatment, as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function; (v) virus infection such as HIV and mumps; (vi) toxins and other environmental/lifestyle factors: cigarette smoking, toxins (e.g., 4-vinylcyclohexene diepoxide), and other environmental factors are associated with the development of POI. The etiology of a majority of POI cases is not identified, and is believed to be multifactorial. Strategies to POI include hormone replacement and infertility treatment. Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women. Embryo cryopreservation, ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments. Primary ovarian insufficiency (POI), commonly referred to as premature ovarian failure (POF), is defined as the occurrence of amenorrhea (for 4 months or more) before the age of 40 in women, accompanied with an increase of serum FSH to menopausal level (usually over 40 IU L 1 , obtained at least 1 month apart), and estradiol levels less than 50 pg mL 1 (which indicate hypoestrogenism) [1]. Primary ovarian insufficiency is first brought to light by Fuller Albright in 1942, who emphasized that the end stage of ovarian function is the primary defect rather than abnormality in gonadotropin secretion [2], and avoided the discomforting and inaccurate stressing on "failure", like death-sentence for ovarian function and conception.Menopause is a destined phase of women, which is expected to occur at around the age of (50±4) years in US women [3]. The age of 40 is two standard deviations below this average [4]. With an incidence of 1% in women under the age of 40, and 0.1% in women under the age of 30 [5], POI renders patients estrogen deficiency and anovulation, resulting in vasomotor symptoms (hot flashes and night sweats), atrophic vaginitis, dyspareunia, primary or secondary amenorrhea, and infertility. 76% of POI cases developed after normal puberty and establishment of regular menses [6]. Some of such conditions occur after stopping...

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“…It has been generally admitted that galactose and its metabolites could be toxic to the ovary (1)(2). This generally leads to more or less severe hypergonadotropic hypogonadism.…”

Section: Introductionmentioning

confidence: 99%

Pregnancy and Delivery After Stimulation with rFSH of a Galatosemia Patient Suffering Hypergonadotropic Hypogonadism: Case Report

Ménézo

Lescaille

Nicollet

et al. 2004

J Assist Reprod Genet

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Purpose : To determine if hypergonadotropic hypogonadism related to galactosemia could be linked to anomaly of the circulating FSH. A 26-year-old woman, suffering GALT (Galactoso-1-phosphate uridyltransferase) had a premature ovarian failure with amenorrhea since the age of 19. The circulating level for FSH was 83 and 34 mU/mL for LH. Methods : After treatment with a hormonal substitution cycle including estradiol and progesterone, the patient underwent stimulations with recombinant FSH. The first cycle, one 16-mm diameter follicle and the second cycle one follicle of 17.5 mm of diameter were obtained at the time of ovulation induction. Results : The patient conceived and delivered a female baby weighting 3.38 kg after the second stimulation protocol. Conclusions : The impact of galactosemia on the ovary seems rather related to the absence of recognition of circulating FSH by its receptor and not to a toxic alteration of the ovary by itself as it is currently reported. The rFSH treatment following hormonal substitution cycles allows to overcome infertility problems.

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Hypergonadotropic Hypogonadism in Female Patients with Galactosemia

Cited by 33 publications

References 0 publications

Galactose Metabolism in Human Ovarian Tissue

Galactose Metabolism in Human Ovarian Tissue

An update on primary ovarian insufficiency

Pregnancy and Delivery After Stimulation with rFSH of a Galatosemia Patient Suffering Hypergonadotropic Hypogonadism: Case Report

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