病因尚不明确。[9]Briend A. Kwashiorkor: still an enigma - the search must go on. CMAM Forum Technical Brief. December 2014. [internet publication].http://files.ennonline.net/attachments/2314/Kwashiorkor-still-an-enigma-CMAM-Forum-Dec-2014.pdf 导致恶性营养不良的最常见原因是以玉米或木薯为主食的膳食结构。 该病并非由母乳喂养时间过长造成。[10]Scrimshaw NS. Fifty-five year personal experience with malnutrition worldwide. Annu Rev Nutr. 2007;27:1-18.http://www.ncbi.nlm.nih.gov/pubmed/17506667?tool=bestpractice.com[11]Cousens S, Nacro B, Curtis V, et al. Prolonged breast-feeding: no association with increased risk of clinical malnutrition in young children in Burkina Faso. Bull World Health Organ. 1993;71(6):713-22.http://whqlibdoc.who.int/bulletin/1993/Vol71-No6/bulletin_1993_71(6)_713-722.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/8313489?tool=bestpractice.com 不认为蛋白质摄入量不足或膳食中抗氧化剂水平较低是导致恶性营养不良的主要因素,因为消瘦症患儿的膳食也存在同样的缺乏。[12]Lindtjorn B. Famine in Ethiopia 1983-1985: kwashiorkor and marasmus in four regions. Ann Trop Paediatr. 1987 Mar;7(1):1-5.http://www.ncbi.nlm.nih.gov/pubmed/2438995?tool=bestpractice.com[13]Kondakis XG, Marealle AL, Kazungu M. Cross-sectional studies on protein-calorie malnutrition in Tanganyika. J Trop Med Hyg. 1964 Sep;67:224-9.http://www.ncbi.nlm.nih.gov/pubmed/14200811?tool=bestpractice.com[14]Excler JL, Nicolas E, Mojon M. Protein-energy malnutrition in an urban African milieu (Togo): etiologic factors in kwashiorkor and marasmic-kwashiorkor. Med Trop (Mars). 1985 Apr-Jun;45(2):155-61.http://www.ncbi.nlm.nih.gov/pubmed/3927104?tool=bestpractice.com
与未患恶性营养不良的营养不良儿童或健康儿童相比,已发现罹患恶性营养不良的儿童血清和肝脏中的黄曲霉毒素水平更高。 然而,有证据表明,黄曲霉毒素水平与恶性营养不良之间的相关性因地理区域而异,恶性营养不良也见于无证据表明曾摄入黄曲霉毒素的人群中。[15]Hendrickse RG, Coulter JB, Lamplugh SM, et al. Aflatoxins and kwashiorkor. Epidemiology and clinical studies in Sudanese children and findings in autopsy liver samples from Nigeria and South Africa. Bull Soc Pathol Exot Filiales. 1983 Nov;76(5):559-66.http://www.ncbi.nlm.nih.gov/pubmed/6673848?tool=bestpractice.com[16]Hatem NL, Hassab HM, Abd Al-Rahman EM, et al. Prevalence of aflatoxins in blood and urine of Egyptian infants with protein-energy malnutrition. Food Nutr Bull. 2005 Mar;26(1):49-56.http://www.ncbi.nlm.nih.gov/pubmed/15810799?tool=bestpractice.com[17]Hendrickse RG. Kwashiorkor and aflatoxins (review). J Pediatr Gastroenterol Nutr. 1988 Sep-Oct;7(5):633-6.http://www.ncbi.nlm.nih.gov/pubmed/3054037?tool=bestpractice.com
根据人们过去 100 年来所做的假设,蛋白质缺乏、低白蛋白血症和过度氧化应激是导致恶性营养不良的原因。[18]Golden MH. Protein deficiency, energy deficiency, and the oedema of malnutrition. Lancet. 1982 Jun 5;1(8284):1261-5.http://www.ncbi.nlm.nih.gov/pubmed/6123017?tool=bestpractice.com[19]Williams CD. Kwashiorkor: a nutritional disease of children associated with a maize diet. 1935. Bull World Health Organ. 2003;81(12):912-3.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572388/pdf/14997245.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/14997245?tool=bestpractice.com[20]Sive AA, Dempster WS, Rousseau S, et al. Bone marrow and chelatable iron in patients with protein energy malnutrition. S Afr Med J. 1996 Nov;86(11):1410-3.http://www.ncbi.nlm.nih.gov/pubmed/8980561?tool=bestpractice.com[21]Manary MJ, Leeuwenburgh C, Heinecke JW. Increased oxidative stress in kwashiorkor. J Pediatr. 2000 Sep;137(3):421-4.http://www.ncbi.nlm.nih.gov/pubmed/10969271?tool=bestpractice.com[22]Golden MH, Golden BE, Jackson AA. Albumin and nutritional edema. Lancet. 1980 Jan 19;1(8160):114-6.http://www.ncbi.nlm.nih.gov/pubmed/6101456?tool=bestpractice.com 然而,给予高风险儿童蛋白质和抗氧化剂膳食补充剂,并未降低他们罹患恶性营养不良的风险,而且,即使采用蛋白质含量受限的饮食,水肿也会消退。[23]Ciliberto H, Ciliberto M, Briend A, et al. Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial. BMJ. 2005 May 14;330(7500):1109.http://www.bmj.com/content/330/7500/1109.longhttp://www.ncbi.nlm.nih.gov/pubmed/15851401?tool=bestpractice.com
最近感染麻疹被认为是危险因素之一,另外,经常有腹泻诱发恶性营养不良的报告。
社会和经济危险因素也会诱发该病,其中包括中止母乳喂养、出生顺序靠后、免疫接种不完整。 家庭环境动荡(例如,父母死亡、未与父母一起生活、抚养人未婚、母亲年纪较小、居住在临时住所或父母没有土地等)也被认为是导致儿童罹患恶性营养不良的原因,但有待确认。[10]Scrimshaw NS. Fifty-five year personal experience with malnutrition worldwide. Annu Rev Nutr. 2007;27:1-18.http://www.ncbi.nlm.nih.gov/pubmed/17506667?tool=bestpractice.com[12]Lindtjorn B. Famine in Ethiopia 1983-1985: kwashiorkor and marasmus in four regions. Ann Trop Paediatr. 1987 Mar;7(1):1-5.http://www.ncbi.nlm.nih.gov/pubmed/2438995?tool=bestpractice.com
4 岁以上的儿童若罹患恶性营养不良,则潜在的结核病 (TB) 或 HIV 感染是较常见的病因。 没有证据表明 HIV 是直接原因,但恶性营养不良与贫穷、口腔病变易感性、持续腹泻、肠病、吸收不良、肠道菌群过度生长均有关系。[24]Kessler L, Daley H, Malenga G, et al. The impact of the human immunodeficiency virus type 1 on the management of severe malnutrition in Malawi. Ann Trop Paediatr. 2000 Mar;20(1):50-6.http://www.ncbi.nlm.nih.gov/pubmed/10824214?tool=bestpractice.com
TB 可能表现为对通常的治疗干预无反应的恶性营养不良,特别是在年龄较大的儿童中,这种情况下,应该在鉴别诊断中考虑 TB。
在肠微生物群探查方面的宏基因组学进展表明,患有恶性营养不良的儿童可能存在年龄依赖性微生物群成熟延迟,这种延迟可能出现在恶性营养不良发生之前。 对于一个小鼠模型,恢复缺失的特定细菌种类有助于营养恢复。[25]Smith MI, Yatsunenko T, Manary MJ, et al. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science. 2013 Feb 1;339(6119):548-54.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667500/http://www.ncbi.nlm.nih.gov/pubmed/23363771?tool=bestpractice.com[26]Reyes A, Blanton LV, Cao S, et al. Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. Proc Natl Acad Sci USA. 2015 Sep 22;112(38):11941-6.http://www.pnas.org/content/112/38/11941.fullhttp://www.ncbi.nlm.nih.gov/pubmed/26351661?tool=bestpractice.com[27]Blanton LV, Charbonneau MR, Salih T, et al. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science. 2016 Feb 19;351(6275).http://www.ncbi.nlm.nih.gov/pubmed/26912898?tool=bestpractice.com