One-carbon metabolism in children with marasmus and kwashiorkor.

BACKGROUND: Kwashiorkor is a childhood syndrome of edematous malnutrition. Its precise nutritional precipitants remain uncertain despite nine decades of study. Remarkably, kwashiorkor's disturbances resemble the effects of experimental diets that are deficient in one-carbon nutrients. This similarity suggests that kwashiorkor may represent a nutritionally mediated syndrome of acute one-carbon metabolism dysfunction. Here we report findings from a cross-sectional exploration of serum one-carbon metabolites in Malawian children. METHODS: Blood was collected from children aged 12-60 months before nutritional rehabilitation: kwashiorkor (N = 94), marasmic-kwashiorkor (N = 43) marasmus (N = 118), moderate acute malnutrition (N = 56) and controls (N = 46). Serum concentrations of 16 one-carbon metabolites were quantified using LC/MS techniques, and then compared across participant groups. FINDINGS: Twelve of 16 measured one-carbon metabolites differed significantly between participant groups. Measured outputs of one-carbon metabolism, asymmetric dimethylarginine (ADMA) and cysteine, were lower in marasmic-kwashiorkor (median µmol/L (± SD): 0·549 (± 0·217) P = 0·00045 & 90 (± 40) P < 0·0001, respectively) and kwashiorkor (0·557 (± 0·195) P < 0·0001 & 115 (± 50) P < 0·0001), relative to marasmus (0·698 (± 0·212) & 153 (± 42)). ADMA and cysteine were well correlated with methionine in both kwashiorkor and marasmic-kwashiorkor. INTERPRETATION: Kwashiorkor and marasmic-kwashiorkor were distinguished by evidence of one-carbon metabolism dysfunction. Correlative observations suggest that methionine deficiency drives this dysfunction, which is implicated in the syndrome's pathogenesis. The hypothesis that kwashiorkor can be prevented by fortifying low quality diets with methionine, along with nutrients that support efficient methionine use, such as choline, requires further investigation. FUNDING: The Hickey Family Foundation, the American College of Gastroenterology, the NICHD, and the USDA/ARS.

Dietary intake of sulfur amino acids and risk of kwashiorkor malnutrition in eastern Democratic Republic of the Congo.

BACKGROUND: Kwashiorkor is an often-fatal type of severe acute malnutrition affecting hundreds of thousands of children annually, but whose etiology is still unknown. Evidence suggests inadequate sulfur amino acid (SAA) status may explain many signs of the condition but studies evaluating dietary protein intake in relation to the genesis of kwashiorkor have been conflicting. We know of no studies of kwashiorkor that have measured dietary SAAs. OBJECTIVES: We aimed to determine whether children in a population previously determined to have high prevalence of kwashiorkor [high-prevalence population (HPP)] have lower dietary intakes of SAAs than children in a low-prevalence population (LPP). METHODS: A cross-sectional census survey design of 358 children compared 2 previously identified adjacent populations of children 36-59 mo old in North Kivu Province of the Democratic Republic of the Congo. Data collected included urinary thiocyanate (SCN), cyanogens in cassava-based food products, recent history of illness, and a 24-h quantitative diet recall for the child. RESULTS: The HPP and LPP had kwashiorkor prevalence of 4.5% and 1.7%, respectively. A total of 170 children from 141 households in the LPP and 169 children from 138 households in the HPP completed the study. A higher proportion of HPP children had measurable urinary SCN (44.8% compared with 29.4%, P < 0.01). LPP children were less likely to have been ill recently (26.8% compared with 13.6%, P < 0.01). Median [IQR] intake of SAAs was 32.4 [22.9-49.3] mg/kg for the LPP and 29.6 [18.1-44.3] mg/kg for the HPP (P < 0.05). Methionine was the first limiting amino acid in both populations, with the highest risk of inadequate intake found among HPP children (35.1% compared with 23.6%, P < 0.05). CONCLUSIONS: Children in a population with a higher prevalence of kwashiorkor have lower dietary intake of SAAs than children in a population with a lower prevalence. Trial interventions to reduce incidence of kwashiorkor should consider increasing SAA intake, paying particular attention to methionine.

Secondary Kwashiorkor Disease in a Patient with Gastric Bypass Surgery and Short Gut Syndrome.

BACKGROUND Kwashiorkor disease is a subtype of severe acute protein malnutrition characterized by peripheral edema associated with hypoalbuminemia and ascites. It can result from both protein deficiency and protein loss. In resource-poor countries, the disease often is caused by inadequate dietary intake, but in resource-rich countries, it can be seen as a rare complication of severe malabsorption. CASE REPORT We present the case of a 60-year-old woman who presented with 1 week of progressive anasarca in the setting of decreased dietary intake and poor tolerance of total parenteral nutrition (TPN). She had a history of Roux-en-Y gastric bypass surgery which was complicated by a strangulated internal hernia that required an exploratory laparotomy and small bowel resection. She subsequently developed short gut syndrome with TPN dependence. Work-up revealed hypoalbuminemia with several micronutrient deficiencies consistent with secondary kwashiorkor disease. With a multidisciplinary approach that included Gastroenterology, Pharmacy, and Nutrition, she was treated with albumin, furosemide, nutritional supplementation, and ultimately rechallenged with TPN. At discharge, her swelling had improved, her weight had decreased, and her albumin improved to the normal range. CONCLUSIONS This case is a unique presentation of secondary kwashiorkor disease. In our patient, the combination of gastric bypass surgery and short gut syndrome with poor TPN tolerance likely led to severe protein malabsorption. This underscores the importance of recognizing the signs and symptoms of kwashiorkor disease and understanding the associated complications so that treatment can be instituted promptly. Furthermore, the case demonstrates how an interdisciplinary approach to management can increase the chance of a successful outcome.

Nutritional Treatment of a Young Infant with Cystic Fibrosis Presenting with Severe Kwashiorkor Dermatosis.

Kwashiorkor in infancy is typically associated to an underlying disease. Edema, a striking feature of this type of malnutrition, can be difficult to assess in this age group. The typical dermatosis of Kwashiorkor is not fully explained the deficiency of one isolated vitamin or micronutrient. This article presents an infant with cystic fibrosis, who developed Kwashiorkor in the third month of life with extensive cutaneous manifestations. An early, individualized and aggressive nutritional intervention with optimized supplementationof sulfur amino acids, vitamins and micronutrients was established, with impressively recovery of overall nutrition and skin manifestations in a relatively short period of time.

Iatrogenic kwashiorkor after distal gastric bypass surgery: the consequences of receiving multinational treatment.

Protein-calorie malnutrition or kwashiorkor is extremely rare after gastric bypass surgery. We report a case of a woman referred to a weight management clinic in the United Kingdom who developed bilateral leg oedema 2 years after gastric bypass surgery in Tunisia. Her serum albumin concentration was 24 g/l, and her body mass index was 16.2 kg/m(2). A review of the postoperative report of her bariatric surgery revealed that she had undergone a distal bypass with anastomosis of the intestine at 1 m proximal to the ileocaecal valve. She required gastrostomy feeding for 6 months before undergoing revisional surgery to a proximal Roux-en-Y gastric bypass in order to restore healthy weight. We recommend that if patients are having their bariatric surgery outside of their country of residence, they should always obtain a copy of the operative notes so that these are readily available if complications arise.

[Adult kwashiorkor: a rare complication of bariatric surgery]. / Kwashiorkor chez l'adulte : une complication rare de la chirurgie bariatrique.

INTRODUCTION: Kwashiorkor is a clinical manifestation of global protein-calorie malnutrition that is described mainly in children in developing countries initially presenting eczema-like skin disease associated with hydrops. OBSERVATION: We report the case of a 44-year-old woman with dark skin who had undergone bariatric surgery for treatment of stage-III obesity without regular monitoring and who was hospitalized in our dermatology department four years later. She had diffuse oedema and asteatotic eczema-like cutaneous lesions on pigmented skin that had developed for two months despite daily application of topical corticosteroids. Clinical signs, the collapse of serum albumin and histopathological analysis of skin tissue were evocative of kwashiorkor. Her symptoms subsided after several weeks of a nutritional programme. DISCUSSION: Kwashiorkor is a clinical entity described chiefly in children in developing countries. Cutaneous involvement comprising asteatotic eczema-like skin associated with diffuse oedema is prominent. Treatment with protein supplementation alone is effective and avoids many complications such as infections and haemodynamic disorders. Obesity is a serious and common disease in Western countries affecting one third of the world's population, and for which treatment with bariatric surgery may be indicated. Without regular monitoring, this surgery can cause severe protein deficiency. Consequently, in the future there will seemingly be a greater likelihood of kwashiorkor in adults as an iatrogenic complication of obesity treatment. Its semiology needs to be underlined because of the simplicity and efficacy of treatment.

The effect of 17ß-estradiol on cutaneous wound healing in protein-malnourished ovariectomized female mouse model.

Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promotes cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17ß-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17ß-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.

Alterações cutâneas no Kwashiorkor: relato de caso de um homem adulto após cirurgia abdominal / Cutaneous manifestations of kwashiorkor: a case report of an adult man after abdominal surgery

Kwashiorkor é um tipo de desnutrição proteico-energética em que há deficiência dietética de proteína, embora a ingestão de calorias se mantenha adequada. As manifestações cutâneas incluem pele xerótica, com aspecto de esmalte descascado, típica coloração avermelhada a branco-acinzentada dos cabelos, o sinal da bandeira e edema mais evidente, nos membros inferiores e na face, dando aspecto de lua cheia. O presente artigo relata o caso de um paciente adulto, do sexo masculino, previamente submetido à duodenopancreatectomia para tratamento de pancreatite crônica associada ao pseudotumor em cabeça de pâncreas que evoluiu com alterações cutâneas de kwashiorkor após tuberculose pulmonar.

Kwashiorkor is a type of protein-energy malnutrition where diet protein deficit is found, in spite of appropriate caloric intake. Cutaneous manifestations include xerosis, with abnormally dry skin that has a flaking enamel paint aspect, a typical red to gray-white hair color, the "flag sign" and more evident edema in lower limbs and face, giving it a full moon appearance. This article reports a case of a male adult patient who had undergone Whipple surgery for treatment of chronic pancreatitis associated with pseudotumor of the pancreatic head that progressed to cutaneous manifestations of kwashiorkor after pulmonary tuberculosis.

Cutaneous manifestations of kwashiorkor: a case report of an adult man after abdominal surgery.

Kwashiorkor is a type of protein-energy malnutrition where diet protein deficit is found, in spite of appropriate caloric intake. Cutaneous manifestations include xerosis, with abnormally dry skin that has a flaking enamel paint aspect, a typical red to gray-white hair color, the "flag sign" and more evident edema in lower limbs and face, giving it a full moon appearance. This article reports a case of a male adult patient who had undergone Whipple surgery for treatment of chronic pancreatitis associated with pseudotumor of the pancreatic head that progressed to cutaneous manifestations of kwashiorkor after pulmonary tuberculosis.

Cutaneous presentation of kwashiorkor due to infantile Crohn's disease.

Kwashiorkor is one of the severe forms of protein-energy malnutrition. Many characteristic dermatoses can be seen in children suffering from kwashiorkor, and some are pathognomonic. Here, we report an infant who presented with diarrhea and skin signs of kwashiorkor, and duodenal biopsy was consistent with Crohn's disease. The patient was treated with prednisolone administered orally in a tapering course plus azathioprine, in addition to nutritional supplementation. The general condition of the patient quickly improved and his skin lesions completely resolved within 2 weeks. Kwashiorkor is a serious potentially fatal disease that occurs less often in developed countries leading to low index of suspicion by physicians and pediatricians in those regions. Occasionally, dermatologists have the rare chance of alerting pediatricians to the diagnosis of kwashiorkor, thus making a difference in the care of this disease.

Combination of type 2 diabetes and malnutrition worsened by anastomotic stenosis and pancreas atrophy following resection of pancreas head.

A 77-year-old Japanese man was admitted due to hypoglycemia induced by small amount of insulin. He was diagnosed type 2 diabetes in 1978 and the pancreatic cancer in 1993. Resection of the pancreas head and duodenum was performed. Subsequently, anastomotic stenosis appeared to induce appetite loss. His flavor for carbohydrate-rich food accelerated protein malnutrition. Fatty liver and pancreas atrophy were diagnosed in 1999. After he was diagnosed as secondary kwashiorkor, nasal feeding of protein-rich food improved his fatty liver as well as his general condition rapidly. Anastomotic stenosis and pancreas atrophy contributed to a combination of type 2 diabetes and kwashiorkor.

Doll-like face: is it an underestimated clinical presentation of cystic fibrosis?

UNLABELLED: Cystic fibrosis (CF) is the most prevalant inheritable chronic disease in caucasian children. The clinical syndrome of kwashiorkor is well-recognized complication of CF. The edema of the face can be seen in kwashiorkor. As doll-like face is very rare and underestimated clinical presentation of CF patients complicated with hypoproteinemia we evaluated demographic features and laboratory characteristics of 5 patients diagnosed as CF with doll-like face. METHODS: Between June 2005 and January 2008, 115 children were diagnosed as having CF enrolled in our center. Five infants were diagnosed as CF with doll-like face before the age of 6 months participitated in study. RESULTS: The incidence of doll-like face younger than the 6 months of age were 9.4% in our center. 48 infants diagnosed as CF without doll-like face before the age of 6 months participitated in the study as controls (group2). Physical examination revealed doll-like face and pitting edema of lower extremities in group 1. Their weight and length were under the third centile. Laboratory findings of group 1 include: mean hemoglobin 7.6g/dl; mean total protein 4.4 g/dl; albumin 2.3 g/dl. When compared control group in order to; 11.4 g/dl (range 7.6-17.9); 6.2 g/dl (range 4.0-8.8); 4.7 g/dl (range 2.1-5.8). mean hemoglobin, total protein and albumin values were lower in group 1. CONCLUSION: In a subgroup of patients, doll-like face may be the presenting manifestation of CF. Especially in developing countries clinicians should be aware of in patients with malnutrition and doll-like face and CF should be considered in differential diagnosis.

What's new? Investigating risk factors for severe childhood malnutrition in a high HIV prevalence South African setting.

AIM: To identify risk factors for severe childhood malnutrition in a rural South African district with a high HIV/AIDS prevalence. DESIGN: Case-control study. SETTING: Bushbuckridge District, Limpopo Province, South Africa. PARTICIPANTS: 100 children with severe malnutrition (marasmus, kwashiorkor, and marasmic kwashiorkor) were compared with 200 better nourished (>-2 SD weight-for-age) controls, matched by age and village of residence. Bivariate and multivariate analyses were conducted on a variety of biological and social risk factors. RESULTS: HIV status was known only for a minority of cases (39%), of whom 87% were HIV positive, while 45% of controls were stunted. In multivariate analysis, risk factors for severe malnutrition included suspicion of HIV in the family (parents or children) (OR 217.7, 95% CI 22.7-2091.3), poor weaning practices (OR 3.0, 95% CI 2.0-4.6), parental death (OR 38.0, 95% CI 3.8-385.3), male sex (OR 2.7, 95% CI 1.2-6.0), and higher birth order (third child or higher) (OR 2.3, 95% CI 1.0-5.1). Protective factors included a diverse food intake (OR 0.53, 95% CI 0.41-0.67) and receipt of a state child support grant (OR 0.44, 95% CI 0.20-0.97). A borderline association existed for family wealth (OR 0.9 per unit, 95% CI 0.83-1.0), father smoking marijuana (OR 3.9, 95% CI 1.1-14.5), and history of a pulmonary tuberculosis contact (OR 3.2, 95% CI 0.9-11.0). CONCLUSIONS: Despite the increasing contribution of HIV to the development of severe malnutrition, traditional risk factors such as poor nutrition, parental disadvantage and illness, poverty, and social inequity remain important contributors to the prevalence of severe malnutrition. Interventions aiming to prevent and reduce severe childhood malnutrition in high HIV prevalence settings need to encompass the various dimensions of the disease: nutritional, economic, and social, and address the prevention and treatment of HIV/AIDS.

Kwashiorkor and an acrodermatitis enteropathica-like eruption after a distal gastric bypass surgical procedure.

OBJECTIVE: To describe a case of kwashiorkor and an acrodermatitis enteropathica-like eruption associated with zinc deficiency after a distal gastric bypass surgical procedure. METHODS: A case report of a morbidly obese patient who underwent a gastric bypass operation is presented, including clinical, laboratory, and radiologic findings. In addition, the literature on potential nutritional deficiencies after bariatric surgical intervention is reviewed. RESULTS: A 43-year-old woman with a history of morbid obesity underwent a distal Roux-en-Y gastric bypass procedure at an outside institution. Six months later, she presented to our clinic because of abdominal pain, lower extremity edema, and a patchy maculopapular scaling rash. She had not adhered to a vitamin supplementation regimen prescribed postoperatively. Her symptoms progressively worsened, and she was hospitalized for management of severe malnutrition and dehydration. Laboratory tests revealed low levels of albumin, hemoglobin, vitamin A, vitamin D, copper, and zinc and elevated levels of liver enzymes. Anasarca and bowel wall edema were seen on an abdominal computed tomographic scan, and an upper endoscopy revealed a stomal ulcer and a stricture at the site of the gastrojejunal anastomosis. The patient was diagnosed as having kwashiorkor, zinc deficiency, and an acrodermatitis enteropathica-like eruption. Treatment was begun with total parenteral nutrition, which led to alleviation of her symptoms. Approximately 3 months later, she underwent gastric bypass revision but had numerous postoperative complications. CONCLUSION: Kwashiorkor and severe nutritional deficiencies were noted in this patient after a distal gastric bypass surgical procedure. This clinical presentation is uncommon and can be attributed to the increased malabsorption that occurs with distal gastric bypass, the development of mechanical complications, and the inadequacy of nutritional supplementation. After a bariatric operation, careful adherence to follow-up regimens and the involvement of a multidisciplinary team can improve the chances of a successful outcome.

Tropical calcific pancreatitis presenting as kwashiorkor.

Tropical clacific pancreatitis can be accompanied by varying degrees of malnutrition but full-blown kwashiorkor is an extremely rare presentation. We report the case of a 10-year-old male who presented with clinical features of severe kwashiorkor. He had extensive pancreatic clacification and exocrine pancreatic deficiency. The child was treated with pancreatic enzyme replacement, and enteral nutrition supplemented with vitamins and micronutrients. Following therapy, he started gaining weight, the skin changes partly disappeared and his hair resumed its normal black colour.

Cystic fibrosis presenting as kwashiorkor in a Sri Lankan infant.

Growth failure is a common presentation of patients with pancreatic insufficient cystic fibrosis. However, full blown kwashiorkor is extremely rare. Cystic fibrosis is also considered to be rare in the South Asian population. This report describes a Sri Lankan infant with cystic fibrosis who presented with clinical features of severe kwashiorkor.

Malnutrition at age 3 years and lower cognitive ability at age 11 years: independence from psychosocial adversity.

BACKGROUND: Early malnutrition is linked to poor cognition, but long-term effects have not been extensively examined and psychosocial confounds have not always been controlled. OBJECTIVE: To test the hypothesis that malnutrition at age 3 years will be associated with poorer cognitive ability at age 11 years independent of psychosocial confounds. DESIGN: A prospective, longitudinal study of a birth cohort of 1559 children originally assessed at age 3 years for malnutrition (low hemoglobin level, angular stomatitis, kwashiorkor, and sparse, thin hair) and followed up to age 11 years. SETTING AND PARTICIPANTS: A community sample of 1559 children (51.4% boys and 48.6% girls) born between September 1, 1969, and August 31, 1970, in 2 towns in the island of Mauritius, with 68.7% Indians and 25.7% Creoles (African origin). MAIN OUTCOME MEASURES: Verbal and spatial ability measured at ages 3 and 11 years and reading, scholastic ability, and neuropsychologic performance measured at age 11 years. RESULTS: Malnourished children had poorer cognition at both ages. Deficits were stable across time, applied to all sex and ethnic groups, and remained after controlling for multiple measures of psychosocial adversity. Children with 3 indicators of malnutrition had a 15.3-point deficit in IQ at age 11 years. CONCLUSIONS: Malnutrition at age 3 years is associated with poor cognition at age 11 years independent of psychosocial adversity. Promoting early childhood nutrition could enhance long-term cognitive development and school performance, especially in children with multiple nutritional deficits.