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Marasmus

 MarasmusBackground

Marasmus is one of the 3 forms of serious protein-energy malnutrition (PEM). The other 2 forms are kwashiorkor (KW) and marasmic KW. These forms of serious PEM represent a group of pathologic conditions associated with a nutritional and energy deficit occurring mainly in young children from developing countries at the time of weaning. Marasmus is a condition primarily caused by a deficiency in calories and energy, whereas kwashiorkor indicates an associated protein deficiency, resulting in an edematous appearance. Marasmic kwashiorkor indicates that, in practice, separating these entities conclusively is difficult; this term indicates a condition that has features of both.[1, 2]

These conditions are frequently associated with infections, mainly GI. The reasons for a progression of nutritional deficit into marasmus rather than kwashiorkor are unclear and cannot be solely explained by the composition of the deficient diet (ie, a diet deficient in energy for marasmus and a diet deficient in protein for kwashiorkor). The study of these phenomena is considerably limited by the lack of an appropriate animal model. Unfortunately, many authors combine these entities into one, thus precluding a better understanding of the differences between these clinical conditions.

Marasmus is a serious worldwide problem that involves more than 50 million children younger than 5 years. According to the World Health Organization (WHO), 49% of the 10.4 million deaths occurring in children younger than 5 years in developing countries are associated with PEM.

See the image below.

1331341 1331373 984496 1645277tn MarasmusMalnutrition hotspot map. Image courtesy of the World Health Organization (WHO) and United Nations Children’s Fund (UNICEF).

Malnutrition has been a permanent priority of the WHO for decades. Although a higher proportion of severely malnourished children do not survive a significant intercurrent illness, as much as 80% of the overall, unacceptably high, mortality rate may be contributed by mild-to-moderately malnourished children because this cohort is so much higher.[3] Accordingly, newer strategies need not be limited to only severely malnourished children.

Although PEM occurs more frequently in low-income countries, numerous children from higher-income countries are also affected, including children from large urban areas and of low socioeconomic status, children with chronic disease, and children who are institutionalized. Recently, studies of hospitalized children from developed countries have demonstrated an increased risk for PEM. Risk factors include a primary diagnosis of mental retardation, cystic fibrosis, malignancy, cardiovascular disease, end stage renal disease, oncologic disease, genetic disease, neurological disease, multiple diagnoses, PICU admission, or prolonged hospitalization.[4, 5] In these conditions, the challenging nutritional management is often overlooked and underestimated, resulting in an impairment of the chances for recovery and the worsening of an already precarious neurodevelopmental situation.

PEM results in not only high mortality (even for hospitalized children), without any improvement over the last 2 decades, and also results in morbidity, stunted linear growth, and compromised neurological development. The social and economic implications of PEM and its complications are incalculable.

This article focuses mainly on marasmus that results from an insufficient nutritional intake as observed under impaired socioeconomic conditions, such as those present in developing countries. Marasmus is most frequently associated with acute infections (eg, gastroenteritis, respiratory illnesses, measles), chronic illnesses (eg, tuberculosis, HIV infection) or drastic natural or man made conditions (eg, floods, droughts, civil war).

NextPathophysiology

Various extensive reviews of the pathophysiological processes resulting in marasmus are available. Unlike kwashiorkor, the clinical sequelae of marasmus can be considered as an evolving adaptation in a child facing an insufficient energy intake. Marasmus always results from a negative energy balance. The imbalance can result from a decreased energy intake, an increased loss of ingested calories (eg, emesis, diarrhea, burns), an increased energy expenditure, or combinations of these factors, such as is observed in acute or chronic diseases. Children adapt to an energy deficiency with a decrease in physical activity, lethargy, a decrease in basal energy metabolism, slowing of growth, and, finally, weight loss.

Pathophysiological changes associated with nutritional and energy deficits can be described as (1) body composition changes, (2) metabolic changes, and (3) anatomic changes.

PreviousNextBody CompositionBody mass: Body mass is significantly decreased in a heterogeneous way.Fat mass: Fat stores can decrease to as low as 5% of the total body weight and can be macroscopically undetectable. The remaining fat is usually stored in the liver, giving a paradoxical appearance of a fatty liver. Although this is often observed in kwashiorkor, it also occurs to a lesser extent in marasmus. A study from Nigeria examined serum lipids in malnourished children.[6] These authors found that total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol levels were significantly higher in children with kwashiorkor than in those with marasmus. Total body water: The proportion of water content in the body increases with the increased seriousness of PEM (marasmus or kwashiorkor) and is associated with the loss of fat mass, which is poor in water. The proportion of extracellular water also increases, often resulting in edema. Edema is significant in kwashiorkor but can also be present in marasmus or in the frequently encountered mixed forms of PEM. The increase in extracellular water is proportional to the increase in the total body water. During the first days of therapy, part of the extracellular water shifts to the intracellular compartment and part of it is lost in the urine, resulting in the observed initial weight loss with treatment. Protein mass: Mainly represented by muscle and some organs (eg, heart), protein mass can decrease as much as 30% in the most serious forms. The muscle fibers are thin with loss of striation. Muscle cells are atrophic, and muscle tissue is infiltrated with fat and fibrous tissue. Total recovery is long but appears to be possible. Other organ mass: The brain, skeleton, and kidney are preserved, whereas the liver, heart, pancreas, and digestive tract are first affected. Pediatric and adult physiologic change: Finally, physiologic changes are different in infants and children when compared with adults. For example, infants with marasmus have an increased tendency to hypothermia and hypoglycemia, requiring the frequent administration of small meals. This can be explained by the body composition imbalance of children with marasmus in favor of high-energy–consuming organs, such as the brain and kidney, compared with energy-storage organs, such as muscle and fat. Assessment of fat and muscle mass: As described below, assessment of the fat and muscle mass loss can be clinically performed by measuring arm circumference (see image below) or skinfold thickness, such as triceps skinfold. The diagram illustrates the validity of this assessment method. Because arm circumference is relatively constant in healthy children aged 1-5 years, it roughly represents a general assessment of nutritional status. 984494 984496 787tn MarasmusPhysiopathological principle of arm circumference measurement in children aged 1-5 years and the relationship with severity of malnutrition. PreviousNextMinerals and VitaminsPotassium: Potassium is the electrolyte most studied in marasmus. Total body potassium deficit is associated with decreased muscle mass, poor intake, and digestive losses. This potassium deficit, which can reach 15 mEq/kg, contributes to hypotonia, apathy, and impaired cardiac function. Other electrolytes: Plasma sodium concentration is generally within the reference range, but it can be low, which is then a sign of a poor prognosis. However, intracellular sodium level is elevated in the brain, muscle, and red and white blood cells, explaining the sodium excretion in the first days of recovery. Other minerals: A deficit in calcium, phosphorus, and magnesium stores is also observed. Iron deficiency anemia is consistently observed in marasmus. However, in the most serious forms, iron accumulates in the liver, most likely because of the deficit in transport protein. These patients are at higher risk of mortality; therefore, iron is supplemented only after the acute recovery phase is completed. Zinc, selenium, and magnesium are more significantly reduced in kwashiorkor but are also constantly deficient in marasmus. Several studies have shown improved recovery from malnutrition and decreased mortality with supplementation of these 3 micronutrients. A Cochrane review concluded that zinc supplementation is clearly of benefit in children aged 6 months or older with diarrheal diseases in areas where these conditions are an important cause of childhood mortality.[7] Vitamins: Both fat-soluble vitamins (ie, A, D, E, K) and water-soluble vitamins (eg, B-6, B-12, folic acid) must be systematically administered. Vitamin A is essential to retinal function, has a trophic effect on epithelial tissues, and plays a major role as an antioxidant agent. Vitamin A deficit affects visual function (eg, conjunctivitis, corneal ulcer, night blindness, total blindness) and digestive, respiratory, and urinary functions. Furthermore, vitamin A supplementation programs have resulted in decreased mortality and morbidity, in particular, during diarrheal disease and measles.

Vitamin and micronutrient deficiencies can be differentiated in 2 categories listed below. Patients with deficiencies of type 1 nutrients present with late and specific clinical signs. In contrast, patients with deficiencies of type 2 nutrients are difficult to identify because blood levels are unreliable and the clinical signs are nonspecific, such as the growth retardation with mild deficiency and weight loss with significant deficiency. Furthermore, type 2 nutrient deficiencies are often combined. Therefore, these deficiencies are global and require a global nutritional rehabilitation, such as WHO standardized solution.

Below are characteristics of type 1 and type 2 deficiencies, according to Golden from a 1991 report.

Type 1 deficiencies Specific clinical signsClinical signs appear after a latency periodUsed in specific metabolic pathwaysAre independent of one anotherVariable tissue concentrationType 2 deficiencies Nonspecific clinical signsNutrient status related to daily intakeUsed in various organs and metabolic pathwaysNutrient interactionConstant tissue concentration

Below are lists of nutrient classification according to the clinical response to deficiency in type 1, with reduction of tissue concentration, and type 2 with growth deficit.

Type 1 nutrients SeleniumIodineIronCopperCalciumManganeseThiaminRiboflavinAscorbic acidRetinolTocopherolCalciferolFolic acidB-12 vitaminPyridoxineType 2 nutrients SodiumSulfurEssential amino acidsPotassiumSodiumMagnesiumZincPhosphorusWaterPreviousNextMetabolic Changes

The overall metabolic adaptations that occur during marasmus are similar to those in starvation, which have been more extensively investigated. The primary goal is to preserve adequate energy to the brain and other vital organs in the face of a compromised supply. Early on, a rise in gluconeogenesis leads to a perceived increased metabolic rate. As fasting progresses, gluconeogenesis is suppressed to minimize muscle protein breakdown, and ketones derived from fat become the main fuel for the brain.

With chronic underfeeding, the basal metabolic rate decreases. One of the main adaptations to long-standing energy deficiency is a decreased rate of linear growth, yielding permanent stunting. The energy saving is partially attenuated by the diversion of energy from muscle to the more metabolically active organs. Further adaptations to crisis situations, such as significant infections, may have some parallels to those that are observed in a stressed, malnourished animal model.[8] The rise in energy expenditure and urinary nitrogen excretion following surgery were significantly less in malnourished rats. This suggests that malnutrition can impair the ability of the organism to mobilize substrates to respond to stress. However, the healing process in these animals remained normal, indicating the ability to prioritize this biological activity.

Energy metabolism With reduced energy intake, a decrease in physical activity occurs followed by a progressively slower rate of growth. Weight loss initially occurs due to a decrease in fat mass, and afterwards by a decrease in muscle mass, as clinically measured by changes in arm circumference (see image below). 984494 984496 787tn MarasmusPhysiopathological principle of arm circumference measurement in children aged 1-5 years and the relationship with severity of malnutrition. Muscle mass loss results in a decrease of energy expenditure. Reduced energy metabolism can impair the response of patients with marasmus to changes in environmental temperature, resulting in an increased risk of hypothermia. Furthermore, during infection, fever is reduced compared to a well-nourished patient. In case of nutrient deficiency, the metabolism is redirected to vital function (requiring 80-100 kcal/kg/d). During recovery, the energy cost of catch-up growth has to be added (up to 100 kcal/kg/d). At this stage, energy needs can be massive. Protein metabolism: Intestinal absorption of amino acids is maintained, despite the atrophy of the intestinal mucosa. Protein turnover is decreased (as much as 40% in severe forms), and protein-sparing mechanisms regulated by complex hormonal controls redirect amino acids to vital organs. Amino acids liberated from catabolism of muscle are recycled by the liver for the synthesis of essential proteins. Total plasma proteins, including albumin, are decreased, whereas gamma globulins are often increased by the associated infections. Albumin: An albumin concentration lower than 30 g/L is often considered as the threshold below which edema develops from decreased oncotic pressure. However, in marasmus, albumin concentration can occasionally be below this value without edema. Prealbumin concentration is a sensitive index of protein synthesis. It decreases with decreased protein intake and rapidly increases in a few days with appropriate nutritional rehabilitation. Insulinlike growth factor 1 (IGF-1) is another sensitive marker of nutritional status. Carbohydrate metabolism: This has mainly been studied in order to explain the serious and often fatal hypoglycemia that occurs in the initial renutrition phase of children with marasmus. The glucose level is often initially low, and the glycogen stores are depleted. Also, a certain degree of glucose intolerance of unclear etiology is observed, possibly associated with a peripheral resistance to insulin or with hypokalemia. In the initiation of renutrition or in association with diarrhea or infection, a significant risk of profound and even fatal hypoglycemia occurs. Small and frequent meals are recommended, including during the night, to avoid death in the early morning. Furthermore, the digestion of starch is impaired by the decreased production of pancreatic amylase. Lactose malabsorption is frequent but is generally without clinical consequences. In most cases, renutrition using milk is possible. Fat metabolism: Dietary fats are often malabsorbed in the initial phase of marasmus renutrition. The mobilization of fat stores for energy metabolism takes place under hormonal control by adrenaline and growth hormone. Blood lipid levels are usually low, and serious dysregulation of lipid metabolism can occur, mainly during kwashiorkor and rarely during marasmus. PreviousNextAnatomic ChangesDigestive tract

The entire digestive tract from mouth to rectum is affected. The mucosal surface becomes smooth and thin, and secretory functions are impaired. A decrease in gastric hydrochloric acid (HCl) excretion and a slowing of peristalsis is observed, yielding bacterial overgrowth in the duodenum. Proportionally, the digestive tract is the organ system that loses the largest mass during marasmus. However, these important alterations of the digestive tract interfere only moderately with normal nutrient absorption. Therefore, early enteral renutrition is not contraindicated but is encouraged because some of the nutrients necessary for the recovery of the intestinal mucosa are used directly from the lumen.

In addition to the anatomic changes associated with PEM, the frequent intestinal infections by viruses and bacteria and the toxins they produce also contribute to the changes in the digestive tract. Liver volume usually decreases, as do other organ volumes. An enlarged liver suggests the possibility of other diagnoses, such as kwashiorkor or hepatitis. Liver synthetic function is usually preserved, although protein synthesis is decreased, as reflected by the decreased albumin and prealbumin levels. Glycogen synthesis is decreased, further increasing the risk for hypoglycemia. The detoxifying function of the liver is impaired with structural changes in the liver cells. Therefore, drugs that are metabolized by the liver should be administered with caution, and liver function should be monitored.

Endocrine system

Many of the adaptations seen in marasmus are mediated by thyroid hormones, insulin, and growth hormone. As in any stressed state, the adrenergic response is activated (see image below).

984494 984496 1404tn MarasmusHormonal adaptation to the stress of malnutrition. The evolution of marasmus.

This response is functional in marasmus but less so in kwashiorkor. Muscle proteins are converted into amino acids and are used for the hepatic synthesis of lipoproteins. These lipoproteins contribute to the mobilization of triglycerides from the liver. In contrast, during kwashiorkor, this function is impaired, resulting in liver steatosis, which is not usually present in marasmus. However, any precipitating factor, such as gastroenteritis or inappropriate renutrition, can disrupt this fragile adaptive mechanism.

Furthermore, in serious marasmus, a significant degree of hypothyroidism, with a decrease in the size of the thyroid gland and repercussions on the brain function and psychomotor development exists. In less severe forms, the impaired thyroid function has fewer clinical consequences. Insulin levels are low and contribute to a certain degree of glucose intolerance, especially during kwashiorkor. Therefore, high-carbohydrate diets are inappropriate. Growth hormone levels are initially within the reference range, but they progressively decrease with time, explaining the halt in linear growth observed with marasmus.

After initiation of renutrition, the hormonal milieu is reversed allowing for substantial anabolism and a rapid linear growth spurt. However, if the marasmic state has gone on too long, then the adult height is less than the genetic potential. Recently, investigators have obtained data that suggest a role for additional hormones in PEM. Levels of serum gherlin(an appetite stimulating peptide) were increased[9] and serum levels of leptin (a satiety hormone) and IGF-1 were decreased in children with PEM compared with healthy controls.[10]

Hematopoietic system

A moderate normochromic or slightly hypochromic anemia is usually present, with normal RBC size. Iron and folate deficiencies, intestinal parasites, malaria, and other chronic infections exacerbate the anemia. However, iron stores are present in the liver. Therefore, iron supplementation should not be initially implemented. Oral iron is poorly tolerated by the digestive tract. The other blood cells (eg, thrombocytes, WBCs) are also affected, but with generally limited clinical consequences. Blood clotting mechanisms are usually preserved, except in the case of serious vitamin K deficiency.

Immune system

Immune impairment and infections are usually associated with marasmus. Thymus atrophy is a characteristic manifestation of marasmus, but all T lymphocyte–producing tissues are affected. However, B-lymphocyte tissues, such as Peyer patches, the spleen, and the tonsils, are relatively preserved. Cellular immunity is most affected, with a characteristic tuberculin anergy. However, antibody production is maintained. In marasmus, a general acquired immunodeficiency occurs, with a decrease in secretory immunoglobulin A (IgA) and an impairment of the nonspecific local defense system, such as mucosal integrity and lymphokine production. Bacteriemia, candidiasis, and Pneumocystis carinii infection are frequently present. Immune impairment is less frequent with moderate malnutrition. Immunological recovery is generally rapid, except if measles is associated.

Brain and nervous system

Cerebral tissue is usually preserved during marasmus. Brain atrophy with impairment of cerebral functions is only present in severe forms of marasmus. Effects on the brain are more important if malnutrition takes place during the first year of life or during fetal life. Irritability and apathy are characteristic of marasmus but improve rapidly with recovery. The permanent developmental consequences of marasmus are difficult to evaluate. Ongoing studies are evaluating these long-term consequences, as well as the benefit of nutritional supplementation with various vitamins and minerals.

Cardiovascular system

Cardiac muscle fiber is thin, and the contractility of the myofibrils is impaired. Cardiac output, especially systolic function, is decreased in the same proportion as the weight loss. Bradycardia and hypotension commonly occur in severe forms of malnutrition. Electrolyte imbalances present during marasmus modify the ECG findings. With this impaired cardiac function, any increase of intravascular volume during rehydration or blood transfusion can result in a significant cardiac insufficiency. With the rapid metabolic, energy, and electrolyte changes of the initial phase of renutrition, this period is also a period of high risk for arrhythmia or cardiac arrest. Therefore, close clinical monitoring is critical in children with circulatory compromise.

PreviousNextEpidemiologyFrequencyUnited States

Marasmus is rarely reported in American children. In 1995, 228 deaths were attributed to marasmus in the United States. Most of these deaths were in elderly adults, and only 3 occurred in children. However, these data do not include deaths associated with marasmus complicating anorexia nervosa.

Incidence of nonfatal marasmus is unclear in the United States because most patients have an underlying condition, and marasmus is not reported as an admission or discharge diagnosis. However, a report from a tertiary care center in Massachusetts reported prevalence rates of severe (1.3%), moderate (5.8%), and mild (17.4%) acute PEM in hospitalized children, based on the Waterlow criteria.[11] In the same cohort, chronic PEM (deficits in height for age) was found to be severe (5.1%), moderate (7.7%), and mild (14.5%).

Acute (33%) and chronic (64%) malnutrition, based on comparing weight and height with controls, was found among a cohort of 160 children hospitalized with congenital heart disease in a regional pediatric cardiothoracic center at the University of Michigan.[12] Malnutrition was inversely correlated with age and was present in 80% of the hospitalized infants. These studies, as well as reports from Western Europe, suggest that marasmus is underappreciated amongst chronically ill children in the United States.[3, 4]

International

Nearly 30% of humans currently experience one or more of the multiple forms of malnutrition. Close to 50 million children younger than 5 years have PEM, and half of the children who die younger than 5 years are undernourished (see image below). Approximately 80% of these malnourished children live in Asia, 15% in Africa, and 5% in Latin America.[13]

984494 984496 1402tn MarasmusDistribution of 10.4 million deaths among children younger than 5 years in all developing countries. World health Organization (WHO), 1995.

Because as many as 20-30% of severely malnourished children die during treatment by the health services,[14] interest in reporting the prevalence of malnutrition in hospitalized children in different countries has been renewed. A recent review article estimated the prevalence of acute malnutrition over the last 10 years in hospitalized children in Germany, France, the United Kingdom, and the United States to be 6.1-14%; the prevalence is as much as 32% in Turkey.[4] However, a recent German study determined that the prevalence of malnutrition was even higher (24% with 1.7% severe, 4.4% moderate, and 17.7% mild) in a cohort of unselected children admitted to a large tertiary care children’s hospital in 2003-2004.5 Furthermore, a worsening of nutritional status in hospitalized children in Brazil,15 France,16 and Turkey.17

Paradoxically, a massive global epidemic of obesity, especially in countries in rapid economic transition, is simultaneously emerging in children and adolescents.

Mortality/Morbidity

Five million children younger than 5 years die every year of malnutrition. Approximately 70 million present with wasting, and 230 million present with some stunting. Fifty percent of the children in Asia are malnourished, 30% are malnourished in Africa, and 20% are malnourished in Latin America.

Race

No racial predilection in the prevalence of malnutrition is evident, but a strong association with the geographic distribution of poverty is observed.

Sex

No sexual predilection is observed, although, in some parts of the world, cultural practices place girls at a disadvantage for PEM.

Age

Marasmus is more frequent in children younger than 5 years because this period is characterized by increased energy needs and increased susceptibility to viral and bacterial infections. Weaning, which occurs during this period, is often complicated by factors such as geography (eg, drought, poor soil productivity), economy (eg, illiteracy, unemployment), hygiene (eg, access to quality water), public health (eg, number of nurses is more than number of physicians), and culture and dietetics (eg, intrafamily distribution of high-nutrition foods).

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