scholarly journals Neonatal hypoglycemia in the De Morsier syndrome

2018 ◽  
Vol 64 (1) ◽  
pp. 42-44
Author(s):  
Tatiana V. Kovalenko ◽  
Irina N. Petrova ◽  
Tatiana Yu. Tarasova
Keyword(s):  
Gene Mutations ◽  
Severe Hypoglycemia ◽  
Endocrine Disorders ◽  
Free T4 ◽  
Gene Encoding ◽  
Oculomotor Disturbances ◽  
De Morsier Syndrome ◽  
Muscle Hypotonia ◽  
Congenital Hypopituitarism ◽  
Relationship Of

The article discusses the causes and diagnostic criteria of the septo-optic dysplasia or De Morsier syndrome. De Morsier syndrome attracts attention of endocrinologists due to the development secondary hypofunction of the endocrine glands and somatotropic deficiency associated with this disease. Septo-optic dysplasia is a polyetiologic disease. The relationship of the disease with the antenatal influence of alcohol, narcotic substances, neurotropic drugs, significant perinatal infections, maternal endocrine diseases, gene mutations, in particular, mutations in the HESX1 gene, encoding the pituitary transcription factors involved in the embryogenesis of the adenohypophysis. We report a clinical case of the disease accompanied by congenital hypopituitarism symptoms. The disease manifested in the neonatal period. The child had severe hypoglycemia in combination with neurological symptoms in the form muscle hypotonia and oculomotor disturbances. The diagnosis of the De Morsier syndrome was verified by the results of MRI of the brain. Endocrine disorders in this patient were characterized by low levels of ACTH, cortisol, IGF-1, and free T4. The administered therapy corrected endocrine disorders in the child. In summary, septo-optic dysplasia or De Morsier syndrome is the subject to interdisciplinary attention of neonatologists, endocrinologists, neurologists, optometrists, and geneticists.

scholarly journals Neonatal hypoglycemia in the De Morsier syndrome

2018 ◽  
Vol 64 (1) ◽  
pp. 42-44
Author(s):  
Tatiana V. Kovalenko ◽  
Irina N. Petrova ◽  
Tatiana Yu. Tarasova
Keyword(s):  
Gene Mutations ◽  
Severe Hypoglycemia ◽  
Endocrine Disorders ◽  
Free T4 ◽  
Gene Encoding ◽  
Oculomotor Disturbances ◽  
De Morsier Syndrome ◽  
Muscle Hypotonia ◽  
Congenital Hypopituitarism ◽  
Relationship Of

The article discusses the causes and diagnostic criteria of the septo-optic dysplasia or De Morsier syndrome. De Morsier syndrome attracts attention of endocrinologists due to the development secondary hypofunction of the endocrine glands and somatotropic deficiency associated with this disease. Septo-optic dysplasia is a polyetiologic disease. The relationship of the disease with the antenatal influence of alcohol, narcotic substances, neurotropic drugs, significant perinatal infections, maternal endocrine diseases, gene mutations, in particular, mutations in the HESX1 gene, encoding the pituitary transcription factors involved in the embryogenesis of the adenohypophysis. We report a clinical case of the disease accompanied by congenital hypopituitarism symptoms. The disease manifested in the neonatal period. The child had severe hypoglycemia in combination with neurological symptoms in the form muscle hypotonia and oculomotor disturbances. The diagnosis of the De Morsier syndrome was verified by the results of MRI of the brain. Endocrine disorders in this patient were characterized by low levels of ACTH, cortisol, IGF-1, and free T4. The administered therapy corrected endocrine disorders in the child. In summary, septo-optic dysplasia or De Morsier syndrome is the subject to interdisciplinary attention of neonatologists, endocrinologists, neurologists, optometrists, and geneticists.

scholarly journals The FKBP4 Gene, Encoding a Regulator of the Androgen Receptor Signaling Pathway, Is a Novel Candidate Gene for Androgen Insensitivity Syndrome

2020 ◽  
Vol 21 (21) ◽  
pp. 8403
Author(s):  
Erkut Ilaslan ◽  
Renata Markosyan ◽  
Patrick Sproll ◽  
Brian J. Stevenson ◽  
Malgorzata Sajek ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Signaling Pathway ◽  
Gene Mutation ◽  
Gene Mutations ◽  
Androgen Insensitivity Syndrome ◽  
Homologous Gene ◽  
Gene Encoding ◽  
Androgen Insensitivity ◽  
Disorder Of Sexual Development ◽  
Partial Androgen Insensitivity Syndrome

Androgen insensitivity syndrome (AIS), manifesting incomplete virilization in 46,XY individuals, is caused mostly by androgen receptor (AR) gene mutations. Therefore, a search for AR mutations is a routine approach in AIS diagnosis. However, some AIS patients lack AR mutations, which complicates the diagnosis. Here, we describe a patient suffering from partial androgen insensitivity syndrome (PAIS) and lacking AR mutations. The whole exome sequencing of the patient and his family members identified a heterozygous FKBP4 gene mutation, c.956T>C (p.Leu319Pro), inherited from the mother. The gene encodes FKBP prolyl isomerase 4, a positive regulator of the AR signaling pathway. This is the first report describing a FKBP4 gene mutation in association with a human disorder of sexual development (DSD). Importantly, the dysfunction of a homologous gene was previously reported in mice, resulting in a phenotype corresponding to PAIS. Moreover, the Leu319Pro amino acid substitution occurred in a highly conserved position of the FKBP4 region, responsible for interaction with other proteins that are crucial for the AR functional heterocomplex formation and therefore the substitution is predicted to cause the disease. We proposed the FKBP4 gene as a candidate AIS gene and suggest screening that gene for the molecular diagnosis of AIS patients lacking AR gene mutations.

scholarly journals Functional characterization of a loss-of-function mutant I324M of arginine vasopressin receptor 2 in X-linked nephrogenic diabetes insipidus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lixia Wang ◽  
Weihong Guo ◽  
Chunyun Fang ◽  
Wenli Feng ◽  
Yumeng Huang ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Nephrogenic Diabetes Insipidus ◽  
Functional Characterization ◽  
Gene Mutations ◽  
Biochemical Properties ◽  
Vasopressin Receptor ◽  
Inherited Disease ◽  
Loss Of Function ◽  
Gene Encoding

AbstractX-linked nephrogenic diabetes insipidus (X-linked NDI) is a rare inherited disease mainly caused by lost-of-function mutations in human AVPR2 gene encoding arginine vasopressin receptor 2 (V2R). Our focus of the current study is on exploration of the functional and biochemical properties of Ile324Met (I324M) mutation identified in a pedigree showing as typical recessive X-linked NDI. We demonstrated that I324M mutation interfered with the conformation of complex glycosylation of V2R. Moreover, almost all of the I324M-V2R failed to express on the cell surface due to being captured by the endoplasmic reticulum control system. We further examined the signaling activity of DDAVP-medicated cAMP and ERK1/2 pathways and the results revealed that the mutant receptor lost the ability in response to DDAVP stimulation contributed to the failure of accumulation of cAMP and phosphorylated ERK1/2. Based on the characteristics of molecular defects of I324M mutant, we selected two reagents (SR49059 and alvespimycin) to determine whether the functions of I324M-V2R can be restored and we found that both compounds can significantly “rescue” I324M mutation. Our findings may provide further insights for understanding the pathogenic mechanism of AVPR2 gene mutations and may offer some implications on development of promising treatments for patients with X-linked NDI.

Test for temporal or spatial restrictions in gene product function during the cell division cycle

1983 ◽  
Vol 3 (7) ◽  
pp. 1255-1265
Author(s):  
S K Dutcher ◽  
L H Hartwell
Keyword(s):  
Cell Division ◽  
Gene Product ◽  
Gene Mutations ◽  
Cell Division Cycle ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Product Function ◽  
Complete Cell ◽  
Relationship Of ◽  
Gene Product Function

The ability of a functional gene to complement a nonfunctional gene may depend upon the intracellular relationship of the two genes. If so, the function of the gene product in question must be limited in time or in space. CDC (cell division cycle) gene products of Saccharomyces cerevisiae control discrete steps in cell division; therefore, they constitute reasonable candidates for genes that function with temporal or spatial restrictions. In an attempt to reveal such restrictions, we compared the ability of a CDC gene to complement a temperature-sensitive cdc gene in diploids where the genes are located within the same nucleus to complementation in heterokaryons where the genes are located in different nuclei. In CDC X cdc matings, complementation was monitored in rare heterokaryons by assaying the production of cdc haploid progeny (cytoductants) at the restrictive temperature. The production of cdc cytoductants indicates that the cdc nucleus was able to complete cell division at the restrictive temperature and implies that the CDC gene product was provided by the other nucleus or by cytoplasm in the heterokaryon. Cytoductants from cdc28 or cdc37 crosses were not efficiently produced, suggesting that these two genes are restricted spatially or temporally in their function. We found that of the cdc mutants tested 33 were complemented; cdc cytoductants were recovered at least as frequently as CDC cytoductants. A particularly interesting example was provided by the CDC4 gene. Mutations in CDC4 were found previously to produce a defect in both cell division and karyogamy. Surprisingly, the cell division defect of cdc4 nuclei is complemented by CDC4 nuclei in a heterokaryon, whereas the karyogamy defect is not.

scholarly journals Structure, expression and phylogenetic analysis of the gene encoding actin I in Pneumocystis carinii.

Genetics ◽  
1994 ◽  
Vol 137 (3) ◽  
pp. 743-750 ◽  
Author(s):  
L D Fletcher ◽  
J M McDowell ◽  
R R Tidwell ◽  
R B Meagher ◽  
C C Dykstra
Keyword(s):  
Phylogenetic Analysis ◽  
Essential Gene ◽  
Pneumocystis Carinii ◽  
Comparative Sequence Analysis ◽  
Cdna Clones ◽  
Actin Gene ◽  
Gene Encoding ◽  
Actin Protein ◽  
Relationship Of ◽  
High Degree

Abstract Actin is a major component of the cytoskeleton and one of the most abundant proteins found in eukaryotic cells. Comparative sequence analysis shows that this essential gene has been highly conserved throughout eukaryotic evolution making it useful for phylogenetic analysis. Complete cDNA clones for the actin-encoding gene were isolated and characterized from Pneumocystis carinii purified from immunosuppressed rat lungs. The nucleotide sequence encodes a protein of 376 amino acids. The predicted actin protein of P. carinii shares a high degree of conservation to other known actins. Only one major actin gene was found in P. carinii. The P. carinii actin sequence was compared with 30 other actin sequences. Gene phylogenies constructed using both neighbor-joining and protein parsimony methods places the P. carinii actin sequence closest to the majority of the fungi. Since the phylogenetic relationship of P. carinii to fungi and protists has been questioned, these data on the actin gene phylogeny support the grouping of P. carinii with the fungi.

scholarly journals Clinical syndromes of compression and surgical transection of the pituitary stalk

2018 ◽  
Vol 64 (1) ◽  
pp. 4-13
Author(s):  
Ludmila I. Astafyeva ◽  
Boris A. Kadashev ◽  
Pavel L. Kalinin ◽  
Maxim A. Kutin ◽  
Irina S. Klochkova ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Diabetes Insipidus ◽  
Tumor Resection ◽  
Pituitary Stalk ◽  
Endocrine Disorders ◽  
Free T4 ◽  
Clinical Syndromes ◽  
Hypothalamic Nuclei ◽  
Dopamine Transport ◽  
The Difference

Background. The pituitary stalk (PS) is an anatomical structure consisting of the portal vessel system and axons of the hypothalamic nuclei terminating in the posterior pituitary lobe. Surgical injury or compression (by a tumor or another space-occupying process) of the PS can lead to hypopituitarism, diabetes insipidus, and hyperprolactinemia. However, the literature lacks studies on the extent of these disorders depending on PS injury or compression in clinical practice. Aim. The study aim was to investigate pre- and postoperative endocrine disorders in patients with chiasmo-sellar region (CSR) tumors and the PS compressed and preserved or involuntarily transected during neurosurgery. Material and methods. The PS compressed before surgery was preserved in 82 patients (41 patients with non-functioning endosuprasellar adenoma and 41 — with suprasellar meningioma). The PS was transected during transcranial surgery in 57 patients (46 patients with pituitary stalk craniopharyngioma and 11 patients with non-functioning endosupresellar pituitary adenoma). All patients underwent blood tests for prolactin (PRL), TSH, LH, FSH, free T4, cortisol, testosterone, or estradiol levels before and 6 months after surgery. Results. Hyperprolactinemia was detected in 37.4% of patients with CSR tumors compressing the PS. Elimination of PS compression led to normalization of the PRL level in most patients and was not accompanied by worsening of hypopituitarism symptoms. Transection of the PS resulted in panhypopituitarism in 100% of patients and diabetes insipidus in 93% of cases. There was no evidence of hyperprolactinemia in 58.7% of patients with craniopharyngiomas and 81.9% of patients with non-functioning pituitary adenomas. Conclusion. Given the difference in symptoms, we distinguished two syndromes: PS compression syndrome and PS transection syndrome. Syndrome of PS compression by a CSR tumor was characterized mainly by hyperprolactinemia (37.4% of cases); elimination of PS compression due to tumor resection led to normalization of the PRL level in most patients and was not accompanied by worsening of hypopituitarism symptoms. Syndrome of surgical PS transection in patients with craniopharyngioma (CP) and non-functioning pituitary adenoma (NFPA) manifested as panhypopituitarism in all patients and as permanent diabetes insipidus in most of them. The causes for the absence of hyperprolactinemia in many patients with the transected PS require further research. We can not exclude both adenohypophysis ischemia (due to its impaired blood supply) with partial or complete atrophy of lactotrophic cells and pituitary revascularization with restoration of dopamine transport.

scholarly journals Adrenal Insufficiency Masquerading as Primary Hypothyroidism Following Immune Checkpoint Inhibitors Treatment

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A110-A111
Author(s):  
Michael Salim ◽  
Wafa Dawahir ◽  
Janice L Gilden ◽  
Andriy Havrylyan
Keyword(s):  
Adrenal Insufficiency ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Primary Hypothyroidism ◽  
Adrenal Crisis ◽  
Thyroid Peroxidase ◽  
Endocrine Disorders ◽  
Free T4

Abstract Background: Immune checkpoint inhibitors (ICIs) are novel immunotherapy agents that have been used to treat multiple advanced cancer. Even though they confer potential clinical advantages by regulating immune reactions, they have been linked with serious immune-mediated adverse events. Here we present a case of a patient who was treated with ICIs, Nivolumab (programmed death-1 inhibitor) and Ipilimumab (cytotoxic T lymphocyte antigen-4 inhibitor), and subsequently developed two concurrent immune-related endocrine disorders. Clinical Case: An 83-year-old man with advanced renal cell carcinoma presented with generalized weakness. He had finished four cycles of immunotherapy with Nivolumab and Ipilimumab, and Ipilimumab was discontinued afterward. Two days after the fifth cycle of immunotherapy with Nivolumab, he developed worsening fatigue, nausea, and anorexia. He appeared mildly volume depleted with borderline hypotensive (104/63 mmHg). The rest of the physical exam was unremarkable. Initial tests showed elevated levels of TSH (13.15 uIU/mL, ref 0.45–5.33 uIU/L), reduced levels of free T4 (<0.25 ng/dL, ref 0.58–1.64 ng/dL), free T3 (1.72 pg/mL, ref 2.5–3.9 pg/mL), negative thyroglobulin antibody, and elevated levels of thyroid peroxidase antibody (429 IU/mL, ref <9 IU/mL), thus suggesting primary hypothyroidism. Serum levels of sodium and potassium were unremarkable (136 meQ/L, ref 136–145 mEq/L; 3.6 meQ/L, ref 3.5–5.1 meQ/L respectively). His baseline TSH was normal three months prior to arrival (1.31 uIU/mL) and suppressed one month prior to arrival (0.01 uIU/mL). Immune-related thyroiditis with immune checkpoint inhibitors was suspected. He was given levothyroxine and observed in the hospital. After two days of hospitalization, weakness had slightly improved. However, he still had persistent nausea. He also developed low blood pressure (90/47 mmHg) and mild hyponatremia (133 mEq/L) with a normal potassium level. Further investigation showed low cortisol (1.0 ug/dL, ref 5.0–21.0), low ACTH (13 pg/mL, ref 6–50 pg/mL), cortisol level at 30 and 60 minutes post-cosyntropin stimulation test of 10.8 ug/dL (ref 13.0–30.0 ug/dL) and 14.8 ug/dL (ref 14.0–36.0 ug/dL) respectively, and negative adrenal antibodies, suggesting of secondary adrenal insufficiency due to hypophysitis. The patient was started on hydrocortisone, and his symptoms improved afterward. Conclusion: This case report highlights the common pitfall of managing immune-related endocrine disorders of ICIs. Adrenal insufficiency may present with a broad range of nonspecific symptoms, which could be attributed to hypothyroidism, underlying illness, or medications. Although a rare adverse effect, it is prudent to recognize adrenal insufficiency superimposed on primary hypothyroidism. Introducing thyroxine before replacing glucocorticoids can lead to an adrenal crisis.

scholarly journals Efficacy of Deep Brain Stimulation in a Patient with Genetically Confirmed Chorea-Acanthocytosis

2019 ◽  
Vol 11 (2) ◽  
pp. 199-204
Author(s):  
Alby Richard ◽  
Joey Hsu ◽  
Patricia Baum ◽  
Ron Alterman ◽  
David K. Simon
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Early Adulthood ◽  
Gene Mutations ◽  
Gene Encoding ◽  
Laboratory Findings ◽  
Current State ◽  
Monopolar Stimulation ◽  
The Impact ◽  
Deep Brain

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disease due to mutation of the VPS13A gene encoding the protein chorein. ChAc is a slowly progressive disorder that typically presents in early adulthood, and whose clinical features include chorea and dystonia with involuntary lip, cheek, and tongue biting. Some patients also have seizures. Treatment for ChAc is symptomatic. A small number of ChAc patients have been treated with bilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi), and we now present an additional case. Patient chart, functional measures, and laboratory findings were reviewed from the time of ChAc diagnosis until 6 months after DBS surgery. Here, we present a case of ChAc in a 31-year-old male positive for VPS13A gene mutations who presented with chorea, tongue biting, dysarthria, weight loss, and mild cognitive dysfunction. DBS using monopolar stimulation with placement slightly lateral to the GPi was associated with significant improvement in chorea and dysarthria. This case adds to the current state of knowledge regarding the efficacy and safety of bilateral GPi-DBS for symptomatic control of drug-resistant hyperkinetic movements seen in ChAc. Controlled trials are needed to better assess the impact and ideal target of DBS in ChAc.

scholarly journals Septo-optic dysplasia

2010 ◽  
Vol 68 (3) ◽  
pp. 400-405 ◽  
Author(s):  
Karina de Ferran ◽  
Isla Aguiar Paiva ◽  
Daniel Luiz Schueftan Gilban ◽  
Monique Resende ◽  
Micheline Abreu Rayol de Souza ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Thyroid Stimulating Hormone ◽  
Empty Sella ◽  
Optic Nerve Hypoplasia ◽  
Brain Abnormalities ◽  
Development Delay ◽  
Congenital Condition ◽  
Pituitary Hypoplasia ◽  
De Morsier Syndrome ◽  
Congenital Hypopituitarism

Septo-optic dysplasia (SOD), also referred to as de Morsier syndrome, is a rare congenital condition, characterized by two of the classic triad features: midline brain abnormalities, optic nerve hypoplasia (ONH) and pituitary endocrine dysfunction. We report 5 children with SOD, originally referred to be evaluated due to short stature, who also presented bilateral optic nerve hypoplasia, nystagmus and development delay. In 4 of the patients, we identified neuroimaging abnormalities of the hypothalamo-pituitary axis such as anterior pituitary hypoplasia (3/5), ectopic posterior pituitary (4/5), thin or absent stalk (3/5) and empty sella (1/5). We also encountered diverse pituitary deficiencies: growth hormone (3/5), adrenocorticotropic hormone (3/5), thyroid-stimulating hormone (2/5) and antidiuretic hormone (1/5). Only one child presented intact pituitary function and anatomy. Although rare, SOD is an important cause of congenital hypopituitarism and it should be considered in children with optic nerve hypoplasia or midline brain abnormalities for early diagnosis and treatment.

scholarly journals Prevalence of thyroid dysfunction in patients with polycystic ovarian syndrome: a cross sectional study

2018 ◽  
Vol 7 (8) ◽  
pp. 3055 ◽  
Author(s):  
Deepa Shanmugham ◽  
Sindhu Natarajan ◽  
Arun Karthik
Keyword(s):  
Thyroid Dysfunction ◽  
Polycystic Ovarian Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Function ◽  
Thyroid Stimulating Hormone ◽  
Endocrine Disorders ◽  
Free T4 ◽  
Cross Sectional ◽  
The Mean ◽  
Ovarian Syndrome

Background: Polycystic ovary syndrome (PCOS) and thyroid disorders are two of the most common endocrine disorders in the general population. Both of these endocrine disorders share common predisposing factors, gynaecological features and have profound effect on reproductive function in women. The aim of this study is to study the prevalence of thyroid dysfunction in patients with polycystic ovarian syndrome and to evaluate the relationship between polycystic ovarian syndrome and thyroid dysfunction.Methods: This is a cross sectional observational study done on 100 patients with Poly Cystic Ovarian Syndrome based on Rotterdam’s criteria. The exclusion criteria was hyperprolactinemia, congenital adrenal hyperplasia and virilising tumour. Thyroid function was evaluated by measurement of fasting serum thyroid stimulating hormone (TSH), free thyroxine levels (free T3 and free T4).Results: The mean age of the study patients was 26±4.2 years. Among the study patients, 11% of them had goitre. 18% of the patients with presented with subclinical hypothyroidism. The mean TSH levels in the study patients was 4.62±2.12 mIU/ml. The overall prevalence of thyroid dysfunction was 33% in the study patients with PCOS.Conclusions: This study concludes that the prevalence of hypothyroidism is increased in women with PCOS patients.

Sign in / Sign up

Export Citation Format

Share Document