Decrease In Serum Sodium Concentration Research Articles

Aldosterone Contributes to Vasopressin Escape through Changes in Water and Urea Transport.

Hyponatremia (hypo-osmolality) is a disorder of water homeostasis due to abnormal renal diluting capacity. The body limits the degree to which serum sodium concentration falls through a mechanism called "vasopressin escape". Vasopressin escape is a process that prevents the continuous decrease in serum sodium concentration even under conditions of sustained high plasma vasopressin levels. Previous reports suggest that aldosterone may be involved in the vasopressin escape mechanism. The abilities of aldosterone synthase (Cyp11b2) knockout and wild-type mice to escape from vasopressin were compared. Wild-type mice escaped while the aldosterone synthase knockout mice did not. Both the water channel aquaporin 2 (AQP2) and the urea transporter UT-A1 protein abundances were higher in aldosterone synthase knockout than in wild-type mice at the end of the escape period. Vasopressin escape was also blunted in rats given spironolactone, a mineralocorticoid receptor blocker. Next, the role of the phosphatase, calcineurin (protein phosphatase 2B, PP2B), in vasopressin escape was studied since aldosterone activates calcineurin in rat cortical collecting ducts. Tacrolimus, a calcineurin inhibitor, blunted vasopressin escape in rats compared with the control rats, increased UT-A1, AQP2, and pS256-AQP2, and decreased pS261-AQP2 protein abundances. Our results indicate that aldosterone regulates vasopressin escape through calcineurin-mediated protein changes in UT-A1 and AQP2.

A case of syndrome of inappropriate anti-diuretic hormone during treatment for lung cancer with uncommon EGFR mutations

Syndrome of inappropriate anti-diuretic hormone (SIADH) sometimes occurs in patients with lung cancer, and it has been reported as a complication after chemotherapy with platinum agents. A 55-yearold woman relapsed after right lower lobectomy for adenocarcinoma harboring uncommon EGFR mutations (G719A in exon 18 and L861Q in exon 21). Brain metastases were found seven months after the operation, and subsequent whole brain irradiation followed by oral treatment with afatinib maintained her status for one year. She was subsequently administered erlotinib with bevacizumab as the third-line treatment for refractory meningeal carcinomatosis, but she developed altered consciousness and was transported to the hospital by ambulance. Laboratory evaluation showed a decrease in serum sodium concentration from 142 to 122 mEq/L. Her altered consciousness was improved by the administration of hypertonic saline; however, the patient died 2 months post-treatment. Although SIADH is sometimes seen before or after treatment for lung cancer, this is the first report of the occurrence of SIADH in a patient with uncommon EGFR-mutated lung cancer.

Prevalence of Hyponatremia in an Elderly Population: A Case Study

Hyponatremia is the most frequent electrolyte disorder both in hospitalized and outdoor patients. Elderly patients represent a high-risk group for the occurrence of hyponatremia because age is a strong independent risk factor for hyponatremia. Decreased serum sodium concentration is a rather frequent electrolyte disorder in the elderly population because of the presence of factors contributing to increased antidiuretic hormone, the frequent prescription of drugs associated with hyponatremia and also because of other mechanisms such as the “tea and toast” syndrome[1]. Hyponatremia in elderly subjects is mainly caused by drugs (more frequently thiazides and antidepressants), the syndrome of inappropriate antidiuretic hormone secretion (SIAD) or endocrinopathies; however, hyponatremia is multi-factorial in a significant proportion of patients. Special attention is needed in the elderly population to exclude endocrinopathies as a cause of hyponatremia before establishing the diagnosis of SIAD, which then requires a stepped diagnostic approach to reveal its underlying cause. Hyponatremia is an important and common electrolyte abnormality that can be seen in isolation or, as most often is the case, as a complication of other medical illnesses (eg, heart failure, liver failure, renal failure, pneumonia). The normal serum sodium level in the body is 135-145 mEq/L. Therefore, hyponatremia is defined as a serum sodium level of less than 135 mEq/L. This research is based on the prevalence of hyponatremia in an elderly population. This study indicates an increase in patients of hyponatremia above 60 years of age. This study also tells the increase in number of patients having hyponatremia as well as abnormal creatinine levels.

Epidemiology of Hyponatraemia among Elderly Patients with Lower Respiratory Tract Infection

Background: Decrease in serum sodium concentration is frequent observation among hospitalised elderly patients. The common causes for hyponatremia are degenerative physiology, dehydration, medications and infections. Hence the present study was undertaken to know the extent of hyponatremia among elderly with Lower Respiratory Tract Infections.
 Objectives: The present study was undertaken to assess the prevalence of hyponatremia in lower respiratory tract infection among geriatric age group and to determine the association between severity of hyponatraemia and LRTI.
 Methods: This was hospital based cross sectional study carried out in the Department of General Medicine of a tertiary care teaching hospital situated in north Karnataka, India during November 2016 to May 2018. 100 elderly patients (age e” 60 years) with history of cough for more than four to five days, clinical findings and X-ray findings suggestive of LRTI, were selected for the study.
 Results: In the present study 59% comprised of male whereas females constituted 41%. The prevalence of hyponatraemia among elderly patients with LRTI was 45%. The most common cause of hyponatraemia was GI loss (vomiting) 53.33%, Euvolemic hyponatramia 51.11%. The mean age was 69.99±8.44 years. Most of the patients were aged between 61 to 70 years. .Hyponatraemia was not associated with sex, age and type of LRTI. Duration of hospital stay was significantly longer in patients with hyponatraemia compared to those who did not develop hyponatraemia.
 Conclusion: Hyponatraemia among elderly individuals with LRTI is higher as compared to other age group hence leading to prolonged duration of hospitalisation.
 Bangladesh J Medicine Jan 2020; 31(1) : 13-17

Сравнение энуклеации доброкачественной гиперплазии предстательной железы объемом более 80 см3 гольмиевым и тулиевым лазерами: ретроспективное клиническое исследование с 12-месячным наблюдением

The aim of our study was to evaluate efficiency of thulium laser enucleation of the prostate (ThuLEP) for the treatment of benign prostatic hyperplasia (BPH). A retrospective analysis of 112 patients with BPH who underwent ThuLEP (n=60) or holmium laser enucleation of the prostate (HoLEP) (n=52) at our institution from January 2017 to June 2017 was carried out. The perioperative data and complication rate were assessed. Severity of lower urinary tract symptom (LUTS) was evaluated after 1, 6 and 12 months using International Prostate Symptom Score [I-PSS], quality-of-life [QoL] score and maximum flow rate [Qmax]. To shorten learning curve, we modified the technique and simplified the intervention. To reduce noise during surgery, we performed ThuLEP using Vela XL. There were significant differences in pre- and perioperative parameters, including operative time (113.15+/-12.14 vs. 118.08+/-15.76 min, p=0.46), decrease in serum sodium concentration (3.49+/-0.83 vs. 3.48+/-0.84 mmol/L, P=0.97), hemoglobin drop (1.37+/-0.18 vs. 1.43+/-0.38 g/dL, p=0.65), catheterization time (2.15+/-0.38 vs. 2.27+/-0.39 days, p=0.52) and hospital stay (6.95+/-0.82 vs 7.56+/-1.36 days, p=0.25) between the two groups (ThuLEP and HoLEP). Compared with the HoLEP group, intraoperative noise was lower in ThuLEP group (47.22+/-10.31 vs. 59.45+/-9.65 db, p<0.05). At 1-, 6- and 12 months follow-up, the LUTS severity (I-PSS, QoL score and Qmax) were significantly improved in both groups in comparison with the baseline values. Furthermore, there was no difference in LUTS severity between two groups (p>0.05). ThuLEP is comparable to the holmium laser in terms of efficiency, safety and indications and represent minimally invasive treatment option for patients with LUTS secondary to BPH.

Hyponatremia in the elderly: challenges and solutions.

Decreased serum sodium concentration is a rather frequent electrolyte disorder in the elderly population because of the presence of factors contributing to increased antidiuretic hormone, the frequent prescription of drugs associated with hyponatremia and also because of other mechanisms such as the “tea and toast” syndrome. The aim of this review is to present certain challenges in the evaluation and treatment of hyponatremia in the elderly population and provide practical solutions. Hyponatremia in elderly subjects is mainly caused by drugs (more frequently thiazides and antidepressants), the syndrome of inappropriate antidiuretic hormone secretion (SIAD) or endocrinopathies; however, hyponatremia is multifactorial in a significant proportion of patients. Special attention is needed in the elderly population to exclude endocrinopathies as a cause of hyponatremia before establishing the diagnosis of SIAD, which then requires a stepped diagnostic approach to reveal its underlying cause. The treatment of hyponatremia depends on the type of hyponatremia. Special attention is also needed to correct serum sodium levels at the appropriate rate, especially in chronic hyponatremia, in order to avoid the osmotic demyelination syndrome. In conclusion, both the evaluation and the treatment of hyponatremia pose many challenges in the elderly population.

Differential diagnosis of hyponatraemia: moving forward?

Hyponatraemia is a resident’s nightmare. A water balance disorder disguised as decreased serum sodium concentration. A plethora of diagnostic algorithms seem to have been developed with the sole purpose of getting you lost as quickly as possible. Nothing but untrustworthy parameters to guide you through this dark wood. And when you finally see light at the end of the tunnel, there is always some staff member, alias electrolyte aficionado, who enjoys public interrogation and makes you feel you are back to square one. [...]

Hyponatremia in patients with systemic lupus erythematosus

The aim of this study was to determine whether decreased serum sodium concentration could be associated with the disease activity in SLE. We retrospectively analyzed the data of the two independent cohorts of children and adults with SLE in two centers. Hyponatremia was associated with serum chloride (p = 0.004), albumin (p = 0.002) and SLE disease activity index (SLEDAI) (p = 0.026) in children with SLE. Serum sodium levels were correlated negatively with ESR (p =0.001) and positively with serum albumin levels (p < 0.0001) and C3 (p = 0.008) in children with SLE and those levels were correlated negatively with serum interleukin-6 levels (p = 0.003) in adults with SLE. Independent risk factors for the development of hyponatremia were the decreased serum C3 levels (OR 1.069, p = 0.031), the decreased serum chloride levels (OR 2.054, p = 0.006) and increased erythrocyte sedimentation rate (ESR) (OR 1.066, p = 0.03) in children with SLE and increased C-reactive protein (CRP) (OR 1.480, p = 0.023) in combined cohorts with SLE by multiple logistic regression analyses. Our study firstly showed that hyponatremia could reflect a disease activity and severe inflammation of SLE.

Association Between Small Decrease in Serum Sodium Concentration within the Normal Range and All-Cause and Cardiovascular Mortality in Elderly Adults over 5Years.

To determine the importance of a decrease in serum sodium concentration within the normal range in elderly adults. Prospective cohort. The Korean Longitudinal Study on Health and Aging. Randomly selected, community-based elderly population with a corrected serum sodium level between 135.0 and 145.0mEq/L (N=949). Survival status was determined during 63.3±16.6 months of follow-up. Participants were divided into corrected sodium groups as follows: 73 (7.7%) in Group 1 (sodium 135.0-138.0mEq/L), 635 (66.9%) in Group 2 (sodium 138.1-142.0mEq/L), and 241 (25.4%) in Group 3 (sodium 142.1.0-145.0mEq/L). There were 34 (46.6%) deaths in Group 1, 124 (19.5%) in Group 2, and 52 (21.6%) in Group 3 (P<.001). In a Cox proportional hazards analysis, a 2-mEq/L higher sodium level reduced the risk of death by 14.9% (95% confidence interval (CI)=0.1-27.4%, P=.048). Group 1 had risk of mortality that was 2.7 times as high as that of Group 2 (95% CI=1.76-4.11, P<.001). Participants with a measured sodium level of 138.0mEq/L or less and a corrected sodium level greater than 138.0mEq/L had a better survival rate than those with a measured sodium level of 138.0mEq/L or less and a corrected sodium level of 138.0mEq/L or less. A slightly lower serum sodium concentration within the normal range was a major risk factor for mortality in elderly adults. Sodium level corrected according to serum glucose concentration was a more meaningful risk factor than measured sodium level.

Hyponatremia in Neurotrauma: The Role of Vasopressin.

Hyponatremia is frequent in patients suffering from traumatic brain injury, subarachnoid hemorrhage, or following intracranial procedures, with approximately 20% having a decreased serum sodium concentration to <125 mmol/L. The pathophysiology of hyponatremia in neurotrauma is not completely understood, but in large part is explained by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The abnormal water and/or sodium handling creates an osmotic gradient promoting the shift of water into brain cells, thereby worsening cerebral edema and precipitating neurological deterioration. Unless hyponatremia is corrected promptly and effectively, morbidity and mortality increases through seizures, elevations in intracranial pressure, and/or herniation. The excess mortality in patients with severe hyponatremia (<125 mmol/L) extends beyond the time frame of hospital admission, with a reported mortality of 20% in hospital and 45% within 6 months of follow-up. Current options for the management of hyponatremia include fluid restriction, hypertonic saline, mineralocorticoids, and osmotic diuretics. However, the recent development of vasopressin receptor antagonists provides a more physiological tool for the management of excess water retention and consequent hyponatremia, such as occurs in SIADH. This review summarizes the existing literature on the pathophysiology, clinical features, and management of hyponatremia in the setting of neurotrauma.

Predictors and outcome impact of perioperative serum sodium changes in a high-risk population

The perioperative period may be associated with a marked neurohumoral stress response, significant fluid losses, and varied fluid replacement regimes. Acute changes in serum sodium concentration are therefore common, but predictors and outcomes of these changes have not been investigated in a large surgical population. We carried out a retrospective cohort analysis of 27 068 in-patient non-cardiac surgical procedures in a tertiary teaching hospital setting. Data on preoperative conditions, perioperative events, hospital length of stay, and mortality were collected, along with preoperative and postoperative serum sodium measurements up to 7 days after surgery. Logistic regression was used to investigate the association between sodium changes and mortality, and to identify clinical characteristics associated with a deviation from baseline sodium >5 mmol litre(-1). Changes in sodium concentration >5 mmol litre(-1) were associated with increased mortality risk (adjusted odds ratio 1.49 for a decrease, 3.02 for an increase). Factors independently associated with a perioperative decrease in serum sodium concentration >5 mmol litre(-1) included age >60, diabetes mellitus, and the use of patient-controlled opioid analgesia. Factors associated with a similar increase were preoperative oxygen dependency, mechanical ventilation, central nervous system depression, non-elective surgery, and major operative haemorrhage. Maximum deviation from preoperative serum sodium value is associated with increased hospital mortality in patients undergoing in-patient non-cardiac surgery. Specific preoperative and perioperative factors are associated with significant serum sodium changes.

738 Impact of Serum Sodium Lowering on Systolic Blood Pressure in Hemodialysis Patients

Background: Since the procedure of hemodiafiltration (HDF) accompanies large amounts of ultrafiltration and substitution fluid infusion, the effects on body fluid compartments may be different from hemodialysis (HD). We compared serum sodiumand blood pressures between online-HDF and high-flux HD patients. Methods: Thirty-two out of 101 patients on high-flux HD were voluntarily switched to online-HDF. Their pre- and post-dialysis measurements were compared with the remaining 69 high-flux HD patients Results: The online-HDF group had lower pre- and post-dialysis systolic blood pressures compared with the high-flux HD group (pre-dialysis, 136 + 21 vs. 145 + 19 mmHg, P < 0.05; post-dialysis, 129 + 22 vs. 142 + 25 mmHg, P < 0.05). Pre- and post-dialysis serum sodium concentrations were not significantly different between the online-HDF and high-flux HD groups (pre-dialysis, 138 + 2 mEq/L vs. 137 + 3 mEq/L; post-dialysis, 134 + 2 vs. 134 + 2 mEq/L). However, the decrease in serum sodium concentration was larger in the online-HDF compared with the high-flux HD (3.7 vs. 2.5 mEq/L,P < 0.05). As serum sodium concentration decreased after the dialysis session, pre-dialysis systolic blood pressure (r = 0.317, P < 0.005) and pulse pressure (r = 0.324, P = 0.001) were significantly lowered. The serum sodium lowering also positively correlated with post-dialysis systolic blood pressure (r = 0.304, P < 0.005) and pulse pressure (r = 0.299, P < 0.005). Conclusions: Compared with high-flux HD, online-HDF has a larger serum sodium lowering effect. This may contribute to stabilizing both pre- and post-dialysis systolic blood pressures.

Biological effects of distension media in bipolar versus monopolar resectoscopic myomectomy: A randomized trial

To estimate the effect of 0.9% saline during bipolar resectoscopy and 1.5% glycine during monopolar resectoscopy on hemodynamic, biochemical and hematological parameters. A prospective randomized study in a tertiary care university hospital and comprising of 155 patients scheduled for hysteroscopic myomectomy. They were subjected to bipolar resectoscopic myomectomy utilizing 0.9% saline in group A, and monopolar resectoscopic myomectomy utilizing 1.5% glycine in group B. Perioperative measurements of hemodynamic, hematological, and biochemical changes in all cases were reported. Likewise, intrauterine pressure throughout the different procedures was recorded. intraoperative difference with regards to fluid volume and subsequent systemic changes specially osmolarity. A significant increase of central venous pressure, end diastolic volume, end diastolic index, stroke volume, stroke index, cardiac output, cardiac index, postoperative prothrombin time and postoperative partial thromboplastin time in both groups with positive correlations between the absorbed fluid volume and these measurements in both groups. Moreover, there was a significant decrease in systemic vascular resistance, postoperative hemoglobin concentration, postoperative hematocrit value ratio, postoperative platelet count and postoperative prothrombin concentration in both groups and there were negative correlations between the absorptive fluid volume and these measurements in both groups. There were significant decrease in serum sodium concentration and postoperative serum osmolarity in glycine group (B) with negative correlations between the absorptive fluid volume and both serum sodium concentration and serum osmolarity in glycine group (B). The use of bipolar resectoscope utilizing 0.9% saline as a distention media is not associated with hyponatremia or hyposmolarity unlike monopolar resectoscope utilizing 1.5% glycine distending media in cases with submucous myoma of considerable size.

Life-Threatening Hyponatremia Secondary to an Orocutaneous Fistula

Hyponatremia is defined as a decrease in serum sodium concentration to a level below 130 mmol/L.1 It is the most common electrolyte disturbance seen in clinical medicine, but is a rare cause of direct admission to hospital.2 The many causes of hyponatremia include drug side affects.3 Hyponatremia is often asymptomatic, and is discovered by a routine analysis of serum electrolytes. However, it may present with nonspecific central nervous system, gastrointestinal, or musculoskeletal signs or symptoms.

Effects of acclimation on water and electrolitic disbalance in soldiers during exertional heat stress

Exertional heat stress is a common problem in military services. The aim of this study was to exemine changes in body water and serum concentrations of some electrolites in soldiers during exertional heat stress (EHST), as well as effects of 10-day passive or active acclimation in a climatic chamber. Forty male soldiers with high aerobic capacity, performed EHST either in cool (20 degrees C, 16 degrees C WBGT-wet bulb globe temperature), or hot (40 degrees C, 25 degrees C WBGT) environment, unacclimatized, or after 10 days of passive or active acclimation. The subjects were allowed to drink tap water ad libitum during EHST. Mean skin (Tsk) and tympanic (Tty) temperatures and heart rates (HR) measured physiological strain, while sweat rate (SwR), and serum concentrations of sodium, potassium and osmolality measured changes in water and electrolite status. Blood samples were collected before and immediately after the EHST. Exertional heat stress in hot conditions induced physiological heat stress (increase in Tty, HR, and SwR), with significant decrease in serum sodium concentration (140.6 +/- 1.52 before vs. 138.5 +/- 1.0 mmol/l after EHST, p < 0.01) and osmolality (280.7 +/- 3.8 vs. 277.5 +/- 2.6 mOsm/kg, p < 0.05) in the unacclimatized group. The acclimated soldiers suffered no such effects of exertional heat stress, despite almost the same degree of heat strain, measured by Tty, HR and SwR. In the trained soldiers, 10-day passive or active acclimation in a climatic chamber can prevent disturbances in water and electrolitic balance, i.e. decrease in serum sodium concentrations and osmolality induced by exertional heat stress.

Electrolytes Disturbances and Seizures

Electrolytes Disturbances and Seizures

Neurological impact of vasopressin dysregulation and hyponatremia

Hyponatremia is frequently associated with neurological disease, neurosurgical procedures, and use of psychoactive drugs. Arginine vasopressin (AVP), or antidiuretic hormone, is the principal physiological regulator of water and electrolyte balance, and disruption of the normal AVP response to osmotic stimuli is a common cause of dilutional hyponatremia in neurological disorders. The hyponatremia-induced shift in water from the extracellular to the intracellular compartment can lead to cerebral edema and serious neurological complications, especially if the decrease in serum sodium concentration ([Na+]) is large or rapid. Overly rapid correction of the serum [Na+] may lead to osmotic demyelination and irreversible brain injury. Fluid restriction is considered first-line treatment and pharmacological agents currently used in the treatment of hyponatremia are limited by inconsistent response and adverse side effects. AVP receptor antagonists represent a new approach to the treatment of hyponatremia by blocking tubular reabsorption of water by binding to V2 receptors in the renal collecting ducts, resulting in aquaresis. Initial clinical experience with AVP receptor antagonists for hyponatremia has shown that these agents augment free water clearance, decrease urine osmolality, and correct serum [Na+] and serum osmolality. Controlled clinical trials now underway will help elucidate the role of AVP receptor antagonism in the treatment of hyponatremia.

Markedly Decreased Serum Sodium Concentration in a Patient With Multiple Myeloma

Markedly Decreased Serum Sodium Concentration in a Patient With Multiple Myeloma

Markedly Decreased Serum Sodium Concentration in a Patient With Multiple Myeloma

Markedly Decreased Serum Sodium Concentration in a Patient With Multiple Myeloma

Diagnosis and treatment of maple syrup disease: a study of 36 patients.

To evaluate an approach to the diagnosis and treatment of maple syrup disease (MSD). Family histories and molecular testing for the Y393N mutation of the E1alpha subunit of the branched-chain alpha-ketoacid dehydrogenase allow us to identify infants who were at high risk for MSD. Amino acid concentrations were measured in blood specimens from these at-risk infants between 12 and 24 hours of age. An additional 18 infants with MSD were diagnosed between 4 and 16 days of age because of metabolic illness. A treatment protocol for MSD was designed to 1) inhibit endogenous protein catabolism, 2) sustain protein synthesis, 3) prevent deficiencies of essential amino acids, and 4) maintain normal serum osmolarity. Our protocol emphasizes the enhancement of protein anabolism and dietary correction of imbalances in plasma amino acids rather than removal of leucine by dialysis or hemofiltration. During acute illnesses, the rate of decrease of the plasma leucine level was monitored as an index of net protein synthesis. The treatment protocol for acute illnesses included the use of mannitol, furosemide, and hypertonic saline to maintain or reestablish normal serum sodium and extracellular osmolarity and thereby prevent or reverse life-threatening cerebral edema. Similar principles were followed for both sick and well outpatient management, especially during the first year, when careful matching of branched-chain amino acid intake with rapidly changing growth rates was necessary. Branched-chain ketoacid excretion was monitored frequently at home and branched-chain amino acid levels were measured within the time of a routine clinic visit, allowing immediate diagnosis and treatment of metabolic derangements. 1) Eighteen neonates with MSD were identified in the high-risk group (n = 39) between 12 and 24 hours of age using amino acid analysis of plasma or whole blood collected on filter paper. The molar ratio of leucine to alanine in plasma ranged from 1.3 to 12.4, compared with a control range of 0.12 to 0.53. None of the infants identified before 3 days of age and managed by our treatment protocol became ill during the neonatal period, and 16 of the 18 were managed without hospitalization. 2) Using our treatment protocol, 18 additional infants who were biochemically intoxicated at the time of diagnosis recovered rapidly. In all infants, plasma leucine levels decreased to <400 micromol/L between 2 to 4 days after diagnosis. Rates of decrease of the plasma leucine level using a combination of enteral and parenteral nutrition were consistently higher than those reported for dialysis or hemoperfusion. Prevention of acute isoleucine, valine, and other plasma amino acid deficiencies by appropriate supplements allowed a sustained decrease of plasma leucine levels to the therapeutic range of 100 to 300 micromol/L, at which point dietary leucine was introduced. 3) Follow-up of the 36 infants over >219 patient years showed that, although common infections frequently cause loss of metabolic control, the overall rate of hospitalization after the neonatal period was only 0.56 days per patient per year of follow-up, and developmental outcomes were uniformly good. Four patients developed life-threatening cerebral edema as a consequence of metabolic intoxication induced by infection, but all recovered. These 4 patients each showed evidence that acutely decreased serum sodium concentration and decreased serum osmolarity were associated with rapid progression of cerebral edema during their acute illnesses. Classical MSD can be managed to allow a benign neonatal course, normal growth and development, and low hospitalization rates. However, neurologic function may deteriorate rapidly at any age because of metabolic intoxication provoked by common infections and injuries. Effective management of the complex pathophysiology of this biochemical disorder requires integrated management of general medical care and nutrition, as well as control of several variables that influence endogenous protein anabolism and catabolism, plasma amino acid concentrations, and serum osmolarity.