良性对称性脂肪瘤病-马德龙综合征

马德龙病又称良性对称性脂肪瘤病(Benign Symmetric Lipo-matosis，BSL) 。是一种罕见的脂肪代谢障碍引起的脂肪组织弥漫性、对称性沉积于颈肩部皮下浅筋膜间隙和（或）深筋膜间隙的疾病，患者常因颈部畸形、活动受限、压迫气管致呼吸困难而就诊。

1846年由Brodie首次报道，1888年Madelung第一次总结了33例该病并进行文献报道，因而又被命名为Madelung病。该病在地中海地区发病率最高，多发于中年男性。全世界已有200余例患者有明确文献报道，但国内报道很少。

良性对称脂肪瘤病(BSL)或马德隆氏病是一种罕见的疾病，其特征是弥漫性、无痛性、无包膜的对称脂肪瘤进行性生长。这种疾病的病因仍然未知，尽管在医学文献中它与酒精和尼古丁滥用、代谢紊乱和许多恶性肿瘤有关。据推测，这种疾病有遗传倾向。在这种情况下的管理是手术切除脂肪瘤，大多数情况下分几次进行，但这通常会导致复发。然而，手术切除脂肪瘤可以提供令人满意的患者功能和美容效果。与HIV感染患者的病态肥胖、库欣综合征、血管脂肪瘤病、包膜脂肪瘤、神经纤维瘤病、粘液样脂肪肉瘤、淋巴瘤、唾液腺疾病、Frolich和脂肪瘤病综合征进行鉴别诊断。

​

主要分布区

​

患者颈肩部对侧性的增粗增大

​

​

CT扫描可见颈部脂肪增厚

CT表现

颈项部、下枕部、上背部脂肪组织蓄积增厚，可累及皮下或肌肉间隙，脂肪蓄积处没有包膜形成，蓄积脂肪内可有线状或网状纤维间隔，病变常常左右对称，颈部肌肉可受压、变细，蓄积脂肪组织内可有钙化或骨化。

​

​

​

​

组织病理学

所有不同类型的脂肪瘤病形态学特征基本相同，包括呈小叶或片状分布的、界限不清的、黄色成熟脂肪组织，与正常脂肪外观相同，有时可以浸润至肌肉等其它组织。与一般的脂肪瘤明显不同，本病脂肪团块缺乏完整包膜，常呈结节状或分叶状而无明显的界限，分布呈弥漫性、左右基本对称的特点。

治疗
目前尚无有效办法。外观改善主要依靠外科彻底切除手术，采用类似改良颈清扫手术方法，保留颈部肌肉和器官，沿颈筋膜彻底切除增生脂肪，避免复发。

术后需戒酒，并积极治疗各种伴发疾病。单纯控制饮食和减肥通常无明显效果。也有学者提出，不必追求手术彻底性，仅部分切除或采用吸脂治疗，改善外观即可。

预后因素
手术后有复发倾向。

参考文献：

1Brodie BC. Lectures illustrative of various subjects in pathology and surgery. Longman.; London: 1846: 275– 76.
Google Scholar
2Madelung OW. Über den Fetthals. Langenbecks Archiv Klin Chirurg. 1888. 37: 106- 130.
Google Scholar
3Launois P, Bensaude, F. L'adénolipomatose symmetrique. Bull Soc méd Hop Paris. 1898; 1: 289– 318.
Google Scholar
4Sun Z, Li H. Case report of comorbid alcohol-induced psychotic disorder and Madelung's disease. Shanghai Arch Psychiatry. 2014; 26: 160– 4.
PubMed Google Scholar
5Brea-Garcia B, Cameselle-Teijeiro J, Couto-Gonzalez I et al. Madelung's disease: comorbidities, fatty mass distribution, and response to treatment of 22 patients. Aesthetic Plast Surg. 2013; 37: 409– 16.
View
PubMed Web of Science®

6Stähelin HB, Häuptli W, Gyr N, Bianchi L. Benign symmetric lipomatosis–symptom of alcoholic liver disease. Schweiz Med Wochenschr. 1977; 107: 1753– 5.
CAS PubMed Google Scholar
7Kölble K, Veltman G. Benign symmetrical lipomatosis in women. Association with alcoholic hepatopathy. Hautarzt. 1984; 35: 33– 8.
CAS PubMed Web of Science®

8Enzi G, Inelmen EM, Baritussio A et al. Multiple symmetric lipomatosis: a defect in adrenergic-stimulated lipolysis. J Clin Invest. 1977; 60: 1221– 9.
View
CAS PubMed

9Klopstock T, Naumann M, Schalke B et al. Multiple symmetric lipomatosis: abnormalities in complex IV and multiple deletions in mitochondrial DNA. Neurology. 1994; 44: 862– 6.
View
CAS PubMed

10Berkovic SF, Andermann F, Shoubridge EA et al. Mitochondrial dysfunction in multiple symmetrical lipomatosis. Ann Neurol. 1991; 29: 566– 9.
View
CAS PubMed

11Plummer C, Spring PJ, Marotta R et al. Multiple Symmetrical Lipomatosis–a mitochondrial disorder of brown fat. Mitochondrion. 2013; 13: 269– 76.
View
CAS PubMed

12Fukuhara N. Strokelike episodes in MERRF. Ann Neurol. 1985; 18: 368.
View
CAS PubMed

13Kobayashi J, Nagao M, Miyamoto K, Matsubara S. MERRF syndrome presenting with multiple symmetric lipomatosis in a Japanese patient. Intern Med. 2010; 49: 479– 82.
View
PubMed Web of Science®

14Chong PS, Vucic S, Hedley-Whyte ET et al. Multiple Symmetric Lipomatosis (Madelung's Disease) Caused by the MERRF (A8344G) Mutation: A Report of Two Cases and Review of the Literature. J Clin Neuromuscul Dis. 2003; 5: 1– 7.
View
PubMed Google Scholar
15Enzi G, Busetto L, Sergi G et al. Multiple symmetric lipomatosis: a rare disease and its possible links to brown adipose tissue. Nutr Metab Cardiovasc Dis. 2015; 25: 347– 53.
View
CAS PubMed

16Vila MR, Gamez J, Solano A et al. Uncoupling protein-1 mRNA expression in lipomas from patients bearing pathogenic mitochondrial DNA mutations. Biochem Biophys Res Commun. 2000; 278: 800– 2.
View
CAS PubMed

17Chondronikola M, Porter C, Ogunbileje JO, Sidossis LS. Identification and Quantification of Human Brown Adipose Tissue. Methods Mol Biol. 2017; 1566: 159– 76.
View
CAS PubMed

18Crichton PG, Lee Y, Kunji ER. The molecular features of uncoupling protein 1 support a conventional mitochondrial carrier-like mechanism. Biochimie. 2017; 134: 35– 50.
View
CAS PubMed

19Martins R, Atgie C, Gineste L et al. Increased GDP binding and thermogenic activity in brown adipose tissue mitochondria during arousal of the hibernating garden dormouse (Eliomys quercinus L.). Comp Biochem Physiol A Comp Physiol. 1991; 98: 311– 6.
View
CAS PubMed

20Ricquier D, Bouillaud F, Toumelin P et al. Expression of uncoupling protein mRNA in thermogenic or weakly thermogenic brown adipose tissue. Evidence for a rapid beta-adrenoreceptor-mediated and transcriptionally regulated step during activation of thermogenesis. J Biol Chem. 1986; 261: 13905– 10.
CAS PubMed Web of Science®

21Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue. Int J Obes (Lond). 2010; 34 (Suppl 1): S36- 42.
View
PubMed Web of Science®

22Nisoli E, Regianini L, Briscini L et al. Multiple symmetric lipomatosis may be the consequence of defective noradrenergic modulation of proliferation and differentiation of brown fat cells. J Pathol. 2002; 198: 378– 87.
View
CAS PubMed

23Ceccarelli G, d’Ettorre G, Marchetti F et al. Development of Buffalo Hump in the course of antiretroviral therapy including raltegravir and unboosted atazanavir: a case report and review of the literature. J Med Case Rep. 2011; 5: 70.
View
PubMed

24Urso R, Gentile M. Are ’buffalo hump’ syndrome, Madelung's disease and multiple symmetrical lipomatosis variants of the same dysmetabolism? AIDS. 2001; 15: 290– 1.
View
CAS PubMed

25Lo JC, Mulligan K, Tai VW et al. “Buffalo hump” in men with HIV-1 infection. Lancet. 1998; 351: 867– 70.
View
CAS PubMed

26Heath KV, Hogg RS, Chan KJ et al. Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database. AIDS. 2001; 15: 231– 9.
View
CAS PubMed

27Giralt M, Domingo P, Villarroya F. Adipose tissue biology and HIV-infection. Best Pract Res Clin Endocrinol Metab. 2011; 25: 487– 99.
View
CAS PubMed

28Rodriguez de la Concepcion ML, Domingo JC, Domingo P et al. Uncoupling protein 1 gene expression implicates brown adipocytes in highly active antiretroviral therapy-associated lipomatosis. AIDS. 2004; 18: 959– 60.
View
PubMed Web of Science®

29Guallar JP, Gallego-Escuredo JM, Domingo JC et al. Differential gene expression indicates that ’buffalo hump’ is a distinct adipose tissue disturbance in HIV-1-associated lipodystrophy. AIDS. 2008; 22: 575– 84.
View
CAS PubMed

30Gdynia HJ, Sperfeld AD, Knirsch U et al. Benign symmetric lipomatosis with axonal neuropathy and abnormalities in specific mitochondrial tRNA regions. Eur J Med Res. 2006; 11: 545– 6.
PubMed Web of Science®

31Vankoningsloo S, Piens M, Lecocq C et al. Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: role of fatty acid beta-oxidation and glucose. J Lipid Res. 2005; 46: 1133– 49.
View
CAS PubMed

32Sawyer SL, Cheuk-Him Ng A, Innes AM et al. Homozygous mutations in MFN2 cause multiple symmetric lipomatosis associated with neuropathy. Hum Mol Genet. 2015; 24: 5109– 14.
View
CAS PubMed

33Nicholson GA, Magdelaine C, Zhu D et al. Severe early-onset axonal neuropathy with homozygous and compound heterozygous MFN2 mutations. Neurology. 2008; 70: 1678– 81.