Relative leptin deficiency in children with severe early-onset obesity (SEOO) – results of the Early-onset Obesity and Leptin – German-Polish Study (EOL-GPS)

2020 ◽  
Vol 33 (2) ◽  
pp. 255-263 ◽  
Author(s):  
Agnieszka Zachurzok ◽  
Michael B. Ranke ◽  
Bertram Flehmig ◽  
Katarzyna Jakubek-Kipa ◽  
Katarzyna Marcinkiewicz ◽  
...  
Keyword(s):  
Early Onset ◽  
Leptin Receptor ◽  
Standard Deviation Score ◽  
Tanner Stage ◽  
Serum Levels ◽  
The Body ◽  
Biologically Active ◽  
World Health ◽  
Strong Negative Correlation ◽  
Leptin Deficiency

AbstractBackgroundSevere early-onset obesity (SEOO) in children is a common feature of monogenic obesity. Gene defects of the leptin-melanocortin pathway can be analysed biochemically and genetically. The aim of this study was to search for children with leptin deficiency or biologically inactive leptin in a cohort of children with SEOO and to study associations between leptin parameters and anthropometric data.MethodsThe cohort included n = 50 children with SEOO (22 boys) who were recruited at one of four study centres (Germany: Ulm; Poland: Katowice, Szczecin, Rzeszow) between October 2015 and October 2017. Weight (kg) and height (m) were measured, Tanner stage was obtained and a fasting serum blood sample was taken. Serum levels of total leptin (LEP, ng/mL), biologically active leptin (bioLEP, ng/mL) and soluble leptin receptor (sLEPR, ng/mL) were measured. The body mass index (BMI [kg/m2]), BMI z-score (World Health Organization [WHO]), quotient of bioLEP/LEP and leptin-standard deviation score (LEP-SDS) (Tanner stage, BMI and sex-adjusted) were calculated.ResultsWe did not find any child with leptin deficiency or biologically inactive leptin in our cohort. The serum LEP and bioLEP levels were strongly correlated with age (r = 0.50, p < 0.05) and BMI (r = 0.70; p < 0.0001). Girls had higher LEP and bioLEP levels (49.7 ± 35.9 vs. 37.1 ± 25.5 ng/mL, p > 0.05) as well as lower LEP-SDS than boys (−1.77 ± 2.61 vs. −1.40 ± 2.60, p > 0.05). sLEPR levels were negatively correlated with BMI values (r = −0.44; p < 0.05), LEP (r = −0.39; p < 0.05) and bioLEP levels (r = −0.37; p < 0.05). Interestingly, there was a strong inverse relationship between LEP-SDS and BMI (r = −0.72, p < 0.001).ConclusionsIn this cohort with SEOO, we identified no new cases of children with leptin deficiency or bioinactive leptin. A strong negative correlation between the LEP-SDS and BMI values could be interpreted as relative leptin deficiency in children with SEOO. In case this hypothesis can be confirmed, these children would benefit from a substitution therapy with methionyl human leptin (metreleptin™).

scholarly journals Adipokines and Obesity. Potential Link to Metabolic Disorders and Chronic Complications

2020 ◽  
Vol 21 (10) ◽  
pp. 3570 ◽  
Author(s):  
Katarzyna Zorena ◽  
Olga Jachimowicz-Duda ◽  
Daniel Ślęzak ◽  
Marlena Robakowska ◽  
Małgorzata Mrugacz
Keyword(s):  
The Body ◽  
Biologically Active ◽  
World Health ◽  
Target Cells ◽  
Fatty Tissue ◽  
Chronic Complications ◽  
Overweight People ◽  
Cochrane Database ◽  
Potential Link ◽  
Health Organization

The World Health Organization (WHO) has recognized obesity as one of the top ten threats to human health. It is estimated that the number of obese and overweight people worldwide exceeds the number of those who are undernourished. Obesity is not only a state of abnormally increased adipose tissue in the body, but also of increased release of biologically active adipokines. Adipokines released into the circulating blood, due to their specific receptors on the surface of target cells, act as classic hormones affecting the metabolism of tissues and organs. What is more, adipokines and cytokines may decrease the insulin sensitivity of tissues and induce inflammation and development of chronic complications. Certainly, it can be stated that in an era of a global obesity pandemic, adipokines may gain more and more importance as regards their use in the diagnostic evaluation and treatment of diseases. An extensive search for materials on the role of white, brown and perivascular fatty tissue and obesity-related metabolic and chronic complications was conducted online using PubMed, the Cochrane database and Embase.

scholarly journals Leptin: a pleitropic factor in physiology

2019 ◽  
Vol 4 (2) ◽  
pp. 31
Author(s):  
Fayez A Almabhouh ◽  
Faizatul Isyraqiah Ahmad Muhammad ◽  
Hisham Ibrahim ◽  
Harbindarjeet Singh
Keyword(s):  
Energy Balance ◽  
Sexual Maturation ◽  
Leptin Receptor ◽  
Tertiary Structure ◽  
Serum Levels ◽  
The Body ◽  
Endocrine Function ◽  
Signalling Pathways ◽  
Percentage Body Fat ◽  
Class 1

Leptin, a 16 kDa protein and a product of the ob/ob gene, has a tertiary structure similar to that of a cytokine. It is primarily secreted by white adipose tissue and its levels in the blood correlate positively with percentage body fat. Leptin was first identified in 1994 as a major factor that regulated food intake and energy balance. Leptin in the circulation exists either as a free monomeric hormone or bound to its soluble receptor. Its serum levels usually range from 0.5 to 37.7 ng/ml in males and 2.0 to 45.2 ng/ml in females. The half-life of leptin is between 20 - 30 minutes and it is eliminated mainly by the kidneys. However, research over the last 25 years has revealed numerous other physiological roles for leptin, including roles in inflammation, immune function, neuro-endocrine function, bone metabolism, blood pressure regulation and sexual maturation. Most of these roles have been identified from studies on leptin deficient rodents. Apart from energy balance and sexual maturation, where its role is direct and obvious, its actions on the rest of the other systems are permissive. Actions of leptin are both centrally and peripherally mediated involving receptors that are widely distributed in the body. Six leptin receptor isoforms, belonging to the class 1 cytokine receptor family, have been identified. These receptors are products of the OBR gene. The cellular actions of leptin are mediated through any one of five different signalling pathways that include the JAK-STAT, PI3K, MAPK, AMPK, and the mTOR signalling pathways.

ATO Metabolites in APL an MM Patients Treated According to APL and MAC/DAC Schemes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 921-921
Author(s):  
Helena Podgornik ◽  
Zdenka Slejkovec ◽  
Samo Zver ◽  
Darja Mazej ◽  
Peter Cernelc ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Arsenic Trioxide ◽  
Active Compound ◽  
Active Form ◽  
Serum Levels ◽  
The Body ◽  
Biologically Active ◽  
Atomic Fluorescence Spectrometry ◽  
Dimethylarsinic Acid ◽  
Total Arsenic

Abstract Introduction Arsenic trioxide (ATO) has been shown to be effective in the treatment of acute promyelocytic leukemia (APL) and towards multiple myeloma (MM) cells. Biologically active form of ATO is inorganic arsenic in its trivalent form (AsIII) which is metabolised in more or less active metabolites already in hours after infusion. The major arsenic excretion metabolites are methylated, namelly methylarsonic acid (MA) and dimethylarsinic acid (DMA). Despite that ATO already has an established role in APL treatment, there is still a lack of data on its metabolism especially when it is combined with other active compounds. The aim of our study was to get an insight into ATO metabolism through measurement of its metabolites in urine and total arsenic in blood during treatment according two different protocols. Patients and methods Patients (8 APL, 12 MM) were treated by ATO (administered as 2 h intravenous infusion) during the years 2004 - 2014. APL patients were previously treated according to a standard APL EORTC protocol. In three patients ATO was started immediately after an interruption of treatment due to a differentiation syndrome and in the remaining five patients ATO was started due to relapse. ATO (0.15 mg/L) was administered for i) 50 consecutive days and prolonged for 25 days (5 days/week) after 3 weeks break or for ii) 25 consecutive days repeated after one week break. Majority of 12 MM patients was heavily pretreated, relapsed or refractory. ATO (0.25 mg/kg) infusion was followed by injection of ascorbic acid (1g). Melphalan (0.1 mg/kg) or Dexamethasone (40 mg/kg) was added in MAC or DAC scheme respectively. ATO was given in cycles (4 consecutive days followed by 3 weeks of 2 applications/week). Treatment efficacy was evaluated by measurement of a monoclonal spike except for patients with Bence-Jones type of MM who were only clinically evaluated. The urine samples were taken before ATO infusion and analysed using HPLC separation combined on-line with hydride generation and atomic fluorescence spectrometry. Arsenic species As(III) and As(V) and both methylated metabolites MA and DMA were followed. Total arsenic concentrations in serum were analysed by ICP-MS. Results All APL patients have obtained a stable molecular remission. In contrast, efficacy of ATO treatment in MM patients is difficult to be evaluated due to the patients’ initial poor condition. In three MM patients effect of ATO cannot be evaluated since they deceased during the treatment. In four out of 9 remaining MM patients at least a partial remission was obtained. Differences between both groups, or better between both protocol regimens (consecutive APL or pulse DAC/MAC in MM), are also reflected in As serum levels and in the presence of ATO metabolites in urine. During the therapy the residual As serum levels in APL group were almost two times as big as those in MM group (72,33±16.79 ng/g vs. 45.13±7.2 ng/g). That means that lower daily doses of ATO preserve higher As concentrations in time than pulse therapy with higher doses. In the urine of MAC/DAC group the proportion of DMA was higher than in the patients treated according APL protocol (48.7 ± 14.6 % vs 63.2 ± 10.4%, Figure 1), while proportions of other three metabolites were lower. A higher proportion of the main active component, As(III), was present in the body of APL patients in comparison to MAC/DAC treated MM patiens (17.5 ± 7.4 % vs 8.6 ± 4.5 %; Figure 1). Differences in metabolites between both groups were statistically significant (MA: P = 0.0127; AsIII, DMA, AsIII: P < 0.0001). Figure 1 Main active compound (AsIII) and main excretion ATO metabolite (DMA) in urine of APL and MM patients. Figure 1. Main active compound (AsIII) and main excretion ATO metabolite (DMA) in urine of APL and MM patients. Conclusions APL patients receiving ATO daily reached a sort of a steady state with a peak in As(III) concentration after i.v. infusion and gradual fall of As(III) concentration until the next day’s infusion while concentrations of other metabolites remained relatively stable. MM patients received higher ATO doses in pulses so that decrease of As(III) after initial peak ended in prolonged lower As(III) levels in between infusions. Poor response to ATO treatment in few MM patients can be attributed to their pretreatment status but also to suboptimal treatment protocol. Significantly lower residual serum As levels were observed during DAC/MAC in comparison to daily treatment according to APL protocol. Lower but more frequent doses of ATO, similar to those in APL, may be more effective in MM. Disclosures Off Label Use: Arsenic trioxide, drug with known antimyeloma activity. It was used as salvage options in multiple myeloma pts., in whom all other conventional treatment options were exhausted. Those patients would be otherwise treated only in a paliative way. They all wrote informed consent after we discussed the issue with them.

scholarly journals Iodine deficiency: socio-economic problems and new approaches to its solution in veterinary medicine

2021 ◽  
Vol 32 ◽  
pp. 04002
Author(s):  
Alexey Yevglevsky ◽  
Andrey Gostev
Keyword(s):  
Mental Retardation ◽  
Iodine Deficiency ◽  
Animal Husbandry ◽  
Preventive Treatment ◽  
The Body ◽  
Biologically Active ◽  
World Health ◽  
Polymer Complex ◽  
The World ◽  
Health Organization

One of the global, vital problems of humanity is iodine deficiency. According to the World Health Organization (WHO), more than 2 billion people live in conditions of iodine deficiency. people: among them, 740 million have endemic goiter, 43 million have mental retardation, more than 6 million. they suffer from cretinism (an extreme degree of mental retardation). Currently, iodine deficiency diseases are the most common non-infectious diseases in the world. What about mammalian animals? In animals, iodine performs the same functions as in humans. Animals, especially agricultural animals, are just as sensitive to iodine deficiency as humans. With a lack of iodine in the body of animals, the biosynthesis of thyroid hormones is disrupted, which leads to a decrease in the intensity of redox processes, as a result of which all types of metabolism are disrupted:-protein, fat, carbohydrate, macro – and microelement, energy. In this regard, the failure of the thyroid gland is accompanied by the development of severe pathobiochemical processes, which, in the end, leads to the clinical manifestation of pathophysiological conditions. Taking into account the fact that in conditions of constant iodine deficiency it is very problematic to ensure the health of productive animals, the issues of prevention of iodine deficiency conditions are economically significant for industrial animal husbandry. It is no accident that in countries experiencing natural iodine deficiency, state programs have been developed that provide for the use of iodine-containing additives in the diets of productive animals. Despite the fact that the simplest and most affordable method of eliminating iodine deficiency in humans and animals is the inclusion of iodized salt in the diet, however, this method can not be used for veterinary purposes. First of all, the feed method of using biologically active additives eliminates the possibility of dosed therapeutic or preventive treatment. On the pages of this article, we draw attention to the emerging prospects for the use of a new iodine-metabolic composition in non-infectious and infectious pathology, based on an iodine polymer complex known in pharmacology as iodinol and succinic acid.

scholarly journals Fundamental Basis of COVID-19 Pathogenesis

2020 ◽  
Vol 21 (2) ◽  
pp. 93-111
Author(s):  
Sergey Brankovich Bolevich ◽  
Peter Frantzevich Litvitsky ◽  
Sergei Vitalievich Grachev ◽  
Sergey Ivanovich Vorobyev ◽  
Alexandra Sergeevna Orlova ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Respiratory Infections ◽  
The Body ◽  
Biologically Active ◽  
World Health ◽  
Ros Generation ◽  
Target Cells ◽  
Atypical Pneumonia ◽  
The World ◽  
Health Organization

AbstractAt the end of 2019, a new coronavirus infection occurred in the People’s Republic of China with an epicentre in the city of Wuhan. On February 11th, 2020, the World Health Organization assigned the official name of the infection caused by the new coronavirus – COVID-19. COVID-19 has affected people from all over the world given that the infection was noted in 200 countries resulting in annunciation of the pandemic situation. Human corona viruses cause mild to moderate respiratory infections. At the end of 2002, a new coronavirus appeared (SARS-CoV), the causal agent of atypical pneumonia, which caused acute respiratory distress syndrome (ARDS). The initial stage of COVID-19 infection is the penetration of SARS-CoV-2 into target cells that have angiotensin converting enzyme type II receptors. The virus enters the body through the respiratory tract and interacts primarily with toll-like receptors (TLRs). The events in SARS-Cov-2 induced infection follow the next scenario: epithelial cells via TLRs recognize and identify SARS-Cov-2, and after that the information is transmitted to the transcriptional NF-κB, which causes expression of the corresponding genes. Activated in this way, the epithelial cells begin to synthesize various biologically active molecules. The results obtained on preclinical material indicate that ROS generation increases and the antioxidant protection decreases, which plays a major role in the pathogenesis of SARS-CoV, as well as in the progression and severity of this respiratory disease.

scholarly journals Myogenin level tends to decrease in adult male cigarette smokers

2020 ◽  
Vol 39 (3) ◽  
pp. 178
Author(s):  
Augustine Chinedu Ihim ◽  
Patrick O. Manafa ◽  
Vincent T. Ekechukwu ◽  
Manafa I. Vera ◽  
Victor N. Chukwudi ◽  
...  
Keyword(s):  
Adult Male ◽  
Tissue Injury ◽  
Serum Levels ◽  
The Body ◽  
Energy Utilization ◽  
World Health ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cross Sectional ◽  
Cigarette Smokers ◽  
Sodium Potassium

<strong>Background</strong><br />The World Health Organization has warned that cigarette smoking is an avoidable risk factor for endothelial injury. Myogenin might play a role in muscle metabolism and energy utilization. Electrolytes and minerals are involved in most cellular activities. The objective of this study was to compare myogenin and electrolyte levels between adult male cigarette smokers (CS) and non-smokers (NS). <br /><br /><strong>Methods</strong><br />A cross-sectional study was conducted involving 90 subjects, consisting of 55 CS and 35 NS. The sandwich enzyme-linked immunosorbent assay was used to determine myogenin levels while the ion-selective electrode method was used to determine electrolyte levels. The levels of sodium, potassium, and chloride and the body mass index (BMI) were measured. Mann-Whitney and independent t-test were used to analyse the data. <br /><br /><strong>Results</strong> <br />The BMI of CS was significantly lower than that of NS (p &lt; 0.05). The mean serum levels of sodium (145.23 ± 1.87), potassium (4.00 ± 0.31) and chloride (103.95 ± 1.60) were significantly higher in the CS than in the NS (these being 142.38 ± 2.49, 3.83 ± 0.33, and 101.48 ± 2.08, respectively) (p&lt;0.05). Myogenin levels (44.24 ± 14.60 pg/mL) tended to decrease in the CS group compared to the NS group (59.66 ± 61.73 pg/mL), but the difference was statistically not significant (p=0.769).<br /><br /><strong>Conclusion</strong> <br />The study demonstrated that higher concentrations of sodium, potassium and chloride with lower concentrations of myogenin in smokers may be associated with higher risk of skeletal muscle tissue injury probably due to the inability of the affected small blood vessels to transport electrolytes to tissues.

scholarly journals Severe Early-Onset Obesity in Three Adult Patients Harboring Inactivating Mutations of the Leptin Receptor Gene

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A37-A37
Author(s):  
Carolina Marques Chaves ◽  
Teresa Kay ◽  
Joao Anselmo
Keyword(s):  
Early Onset ◽  
Leptin Receptor ◽  
Reference Range ◽  
Receptor Gene ◽  
Pubertal Development ◽  
Genetic Diagnosis ◽  
The Body ◽  
Homozygous Mutation ◽  
Genetic Sequencing ◽  
Lepr Gene

Abstract Background: Leptin is secreted by white adipocytes in response to fat storage and binds to leptin receptors (LEPR) expressed all over the body particularly in hypothalamic neurons. This hormone regulates several physiologic functions including energy expenditure and appetite. Clinical Case: We describe the clinical and hormonal findings in 3 adult brothers with body mass index (BMI) of 36.7, 50.7, and 46.1 kg/m2, respectively. There is no history of consanguinity in the family and none of the patients exhibited dysmorphic features. A rapid weight gain was noticed during their first few months of life, associated with permanent hyperphagia. At 2 years old, their BMI was already above 25 kg/m2 (&gt; +3SD), and at 10 years old, it was over 40 kg/m2 (&gt; +3SD). The linear growth was within the expected target heights for their parents. They did not seem to present cognitive impairment. The pubertal development began at 16 to 18 years old, and since then they maintained levels and FSH and LH above the upper limit of normal (15.6±3.7mUI/mL and 12.3±2.2mUI/mL, reference range 1.5–12.4 and 1.7–8.6, respectively), but with normal sexual steroids (estradiol 36.4±16.1pg/mL and total testosterone 445±401ng/dL, reference range 11–44 and 249–836, respectively). The thyroid function was normal and none of the patients suffered from dyslipidemia or diabetes, despite high serum insulin levels 26.4±15.8 mU/L (normal 5–10). Genetic sequencing identified a homozygous mutation of the leptin receptor gene in the 3 brothers: c.2357T&gt; C, p. (Leu786Pro). Their parents were heterozygous for the mutation as well as the patients’ daughters. Homozygous carriers of the mutation presented a significantly higher BMI than their heterozygous family members, 44.5±7.1 Kg/m2 vs 32.2±1.7 Kg/m2 (p=0.023), a significantly increased leptin levels, 80±36.4 ng/ml vs 26.3±9.3 ng/ml (p=0.028), and significantly higher weight, 134.6±16.9 vs 89.2±15,2 kg (p=0.021), respectively. Women had higher BMI than men (42.0 ±12.2 Kg/m2 vs 37.9±7.5 Kg/m2, p=0.496) and also higher percentage of fat (46.4±3.1% vs 34.9±6.8%, p=0.108). Serum levels of leptin in homozygous patients were not significantly higher than those measured in 10 patients with adult-onset morbid obesity, 80± 36.4 ng/ml vs 53.8±24.1 ng/ml, respectively (p=0.149). Therefore, serum leptin is not a useful discriminative maker of LEPR gene mutations. Conclusion: Patients with severe early-onset obesity should have a genetic diagnosis workup. Firstly, because clinical trials with MC4R-agonists have raised expectations regarding the treatment of patients with mutations of the LEPR gene. Secondly, and in contradiction to other reports in the literature, our patients were fertile. Therefore, identification of the mutation allows genetic counseling of these patients and their families, including the possibility of Pre-Natal Diagnosis or Pre-Implantation Genetic Diagnosis.

scholarly journals Secondary Metabolites of Plants as Modulators of Endothelium Functions

2021 ◽  
Vol 22 (5) ◽  
pp. 2533
Author(s):  
Anna Bartáková ◽  
Marie Nováková
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
The Body ◽  
Guanosine Monophosphate ◽  
Biologically Active ◽  
World Health ◽  
Intracellular Calcium Level ◽  
Health Organization ◽  
Active Substances

According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time—from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide–cyclic guanosine monophosphate activation, prostacyclin–cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.

A link between hypothyroidism, obesity and male reproduction

2016 ◽  
Vol 25 (1) ◽  
Author(s):  
Veronica Aiceles ◽  
Cristiane da Fonte Ramos
Keyword(s):  
Thyroid Hormones ◽  
Body Weight Gain ◽  
Inverse Correlation ◽  
Serum Levels ◽  
The Body ◽  
Male Reproduction ◽  
World Health ◽  
Male Factor ◽  
Leptin Receptors ◽  
Health Organization

AbstractHypothyroidism is a condition in which the serum levels of thyroid hormones are below that necessary to carry out physiological functions in the body. Hypothyroidism is related to obesity as an increase in body weight gain is seen in hypothyroid patients. Moreover, an inverse correlation between free thyroxine values and body mass index has been reported. Leptin, a polypeptide hormone produced by adipocytes, was originally thought to be an antiobesity hormone due its anorexic effects on hypothalamic appetite regulation. However, nowadays it is known that leptin conveys information about the nutritional status to the brain being considered a crucial endocrine factor for regulating several physiological processes including reproduction. Since the identification of thyroid hormone and leptin receptors on the testes, these hormones are being recognized as having important roles in male reproductive functions. A clear link exists among thyroid hormones, leptin and reproduction. Both hormones can negatively affect spermatogenesis and consequently may cause male infertility. The World Health Organization (WHO) estimates the overall prevalence of primary infertility ranging from 8 to 15%. The fact that 30% of couples’ inability to conceive is related to a male factor and that the longer hypothyroidism persisted, the greater the damage to the testes, strongly suggest that more studies attempting to clarify both hormones actions directly in the testes need to be conducted specially in cases of congenital hypothyroidism. Therefore, the goal of this review is to highlight the relationship of such hormones in the reproductive system.

A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: metformin treatment shows a beneficial impact on the body mass index

2018 ◽  
Vol 31 (7) ◽  
pp. 815-819
Author(s):  
Mark A. Hilado ◽  
Ruvdeep S. Randhawa
Keyword(s):  
Body Mass Index ◽  
Weight Gain ◽  
Adrenal Insufficiency ◽  
Body Mass ◽  
Early Onset ◽  
The Body ◽  
Biologically Active ◽  
Metformin Treatment ◽  
Hair Pigmentation ◽  
Red Hair

Abstract Background Proopiomelanocortin (POMC) is a complex polypeptide that produces a variety of biologically active substances via cleavage in a tissue-specific manner [Challis BG, Millington GW. Proopiomelanocortin deficiency. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle, 1993–2018], yielding several products including adrenocorticotrophic (ACTH) and melanocyte stimulating hormones (MSH). These peptides have roles in the regulation of food intake, energy homeostasis, adrenal steroidogenesis, melanocyte stimulation and immune modulation. Rare mutations in the POMC gene can lead to ACTH deficiency and thus isolated hypocortisolism. The first cases of POMC mutation were documented by Krude et al. in 1998 [Krude H, Biebermann H, Luck W, Horn R, Brabant G, et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 1998;19:155–7]. Mutations in the POMC gene were linked with a clinical phenotype of adrenal insufficiency, red hair pigmentation, early onset and rapidly progressive obesity, early onset type 2 diabetes, hypothyroidism, hypogonadism and growth hormone deficiency. Case presentation We describe a prepubertal Hispanic boy with a novel homozygous POMC mutation with severe obesity, hypothyroidism, adrenal insufficiency and abnormal reddish hair pigmentation. The patient presented as a 2-year-old with exponential weight gain, abnormal thyroid labs and speech delay. Laboratory testing demonstrated central adrenal insufficiency and genetic testing confirmed a homozygous mutation (nucleotide change c.20_21ins25) in exon 3 of the POMC gene. Replacement therapy with thyroid hormone and hydrocortisone was coupled to a slight decrease in the rate of weight gain, although hyperphagia persisted. Parent-directed nutrition and activity education as well as attempts to restrict access to food resulted in a plateau of the body mass index (BMI). At 4 years of age, metformin treatment was initiated with the patient showing evolving signs of insulin resistance and failure of lifestyle/dietary intervention to adequately decrease the BMI. Over a 3-year metformin treatment span, the BMI decreased from 34.9 kg/m2 to 32.9 kg/m2. Conclusions We demonstrate a possible role for metformin in stemming progressive weight gain, thereby impacting the early onset obesity due to hyperphagia.

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