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Dermatologic Manifestations of Generalized Lipodystrophy Clinical Presentation

  • Author: Camila K Janniger, MD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jun 22, 2016
 

Physical

Two forms of generalized lipodystrophy exist, congenital and acquired, which have different clinical features.

Congenital generalized lipodystrophy

The diagnosis of generalized lipodystrophy often is obvious from birth because of the extraordinary lack of subcutaneous fat. Fat cells are present but are reduced in number and size and contain little fat. Anabolic features are observed at birth, with enlarged visceral organs. Toddlers may have a potentially dangerous hyperplasia of pharyngeal tonsils and adenoids. Lipodystrophy produces a distinctive facies.

A well-defined musculature with prominent superficial veins is one of the earliest manifestations.

Clitoral or penile hypertrophy has been evident at birth, but genitomegaly is not apparent after puberty.

The earliest skin manifestations include AN, eruptive xanthomas, hirsutism, and thick, tightly curled scalp hair that extends nearly to the eyebrows. Hirsutism of the face, neck arms, and legs may be observed at birth in some patients and tends to increase. No special growth of the pubic or axillary hair occurs.

All patients with Lawrence-Seip syndrome and lipodystrophy have AN to some degree. AN can diminish and disappear with puberty and is said to be prominent on the elbows, knees, and waist, as well as the more typical sites of the neck and axillae.

Acromegalic gigantism with advanced bone age and advanced dentition is an early and constant feature. The growth rate is most marked in the first 4 years, and these children may attain more than 90% of their adult growth within the first 10 years of life. Growth subsequently slows, and normal or short stature as adults usually is observed. Lipoatrophy does not affect female breast development at puberty, although females with this congenital lipodystrophy syndrome have a masculine habitus with marked muscularity.

Liver disease with fatty metamorphosis and cirrhosis is another constant feature, and hepatosplenomegaly tends to produce a markedly protuberant abdomen.

Childhood death due to massive GI bleeding has been reported frequently.

Diabetes mellitus usually begins in the teenage years. The diabetes is insulin resistant, and despite poor control of the diabetes, ketosis tends to be absent. Hyperlipemia usually precedes the diabetes.

An increased basal metabolic rate is a frequent finding.

Dilatation of the cerebral ventricular system has been described in most patients with generalized lipodystrophy. Intelligence may range from normal to subnormal.

Kidneys may be enlarged without apparent histologic cause, and renal failure may ensue.

Cardiomegaly frequently is observed with muscle hypertrophy and ventricular disfunction. Asymmetric hypertrophic cardiomyopathy has been described.[7]  Increased chamber size may be demonstrated on echocardiogram with a systolic ejection murmur. Peripheral artery stenosis may be associated with reduced exercise tolerance, cardiac murmurs, and, possibly, pulmonary hypertension. Occasionally, congenital anomalies of the heart, bones, and kidneys also are found. These patients have abnormal autonomic modulation, reflected by an increased heart rate and a pronounced reduction in heart rate variability.[8]

The presence of dental abnormalities such as talon cusps, macrodontia, and aberrant tooth morphology has been described.[9]

Acquired generalized lipodystrophy

Generalized lipodystrophy often is preceded by an illness and, in many instances, an infection. The fat loss becomes apparent either focally or diffusely, usually beginning in adolescence or early adult life.

Most of the features of the congenital form may occur, but in the acquired form, neurologic, cardiac, and renal abnormalities usually are absent. Bone age is normal and genital hypertrophy is absent. AN to varying degrees probably is a constant finding in acquired and congenital forms.

Autoimmune disorders also may be common, including Coombs-positive hemolytic anemia and chronic nephritis; however, great variability exists in the immunologic abnormalities in patients with the acquired form. Patients with the acquired form of generalized lipodystrophy also are prone to infection.

 
 
Contributor Information and Disclosures
Author

Camila K Janniger, MD Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, Rutgers New Jersey Medical School

Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Cris Jagar, MD Staff Physician, Department of Psychiatry, Trinitas Regional Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Albert C Yan, MD Section Chief, Associate Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine

Albert C Yan, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology, Society for Pediatric Dermatology, American Academy of Pediatrics

Disclosure: Nothing to disclose.

References
  1. Patni N, Alves C, von Schnurbein J, Wabitsch M, Tannin G, Rakheja D, et al. A Novel Syndrome of Generalized Lipodystrophy Associated With Pilocytic Astrocytoma. J Clin Endocrinol Metab. 2015 Oct. 100 (10):3603-6. [Medline].

  2. Akinci B, Onay H, Demir T, et al. Natural History of Congenital Generalized Lipodystrophy: A Nationwide Study from Turkey. J Clin Endocrinol Metab. 2016 May 4. jc20161005. [Medline].

  3. Jin J, Cao L, Zhao Z, et al. Novel BSCL2 gene mutation E189X in Chinese congenital generalized lipodystrophy child with early onset diabetes mellitus. Eur J Endocrinol. 2007 Dec. 157(6):783-7. [Medline].

  4. Knebel B, Kotzka J, Lehr S, Hartwig S, Avci H, Jacob S, et al. A mutation in the c-fos gene associated with congenital generalized lipodystrophy. Orphanet J Rare Dis. 2013 Aug 7. 8:119. [Medline]. [Full Text].

  5. Lima JG, Nobrega LH, de Lima NN, do Nascimento Santos MG, Baracho MF, Jeronimo SM. Clinical and laboratory data of a large series of patients with congenital generalized lipodystrophy. Diabetol Metab Syndr. 2016. 8:23. [Medline].

  6. Llamas-Velasco M, Daudén E, Martínez-Peñas G, García-Diez A. Late-Onset Acquired Generalized Lipodystrophy With Muscle Involvement. Actas Dermosifiliogr. 2011 Dec 19. [Medline].

  7. Scatteia A, Pagano C, Pascale C, Guarini P, Marotta G, Perrone-Filardi P, et al. Asymmetric hypertrophic cardiomyopathy in generalized lipodystrophy. Int J Cardiol. 2015 Oct 9. 202:724-725. [Medline].

  8. Faria CA, Moraes RS, Sobral-Filho DC, Rego AG, Baracho MF, Egito ES, et al. Autonomic modulation in patients with congenital generalized lipodystrophy (Berardinelli-Seip syndrome). Europace. 2009 Apr 17. [Medline].

  9. Solanki M, Patil SS, Baweja DK, Noorani H, Pk S. Talon cusps, macrodontia, and aberrant tooth morphology in Berardinelli-Seip syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Jan. 105(1):e41-7. [Medline].

  10. Rego AG, Mesquita ET, Faria CA, et al. [Cardiometabolic abnormalities in patients with berardinelli-Seip syndrome]. Arq Bras Cardiol. 2010 Jan. 94(1):109-18. [Medline].

  11. Al-Attar SA, Pollex RL, Robinson JF, Miskie BA, Walcarius R, Little CH, et al. Quantitative and qualitative differences in subcutaneous adipose tissue stores across lipodystrophy types shown by magnetic resonance imaging. BMC Med Imaging. 2007. 7:3. [Medline].

  12. Mork NJ, Rajka G, Halse J. Treatment of acanthosis nigricans with etretinate (Tigason) in a patient with Lawrence-Seip syndrome (generalized lipodystrophy). Acta Derm Venereol. 1986. 66(2):173-4. [Medline].

  13. Miehle K, Stumvoll M, Fasshauer M. [Lipodystrophy : Mechanisms, clinical presentation, therapy.]. Internist (Berl). 2011 Apr. 52(4):362-373. [Medline].

  14. Moran SA, Patten N, Young JR, Cochran E, Sebring N, Reynolds J, et al. Changes in body composition in patients with severe lipodystrophy after leptin replacement therapy. Metabolism. 2004 Apr. 53(4):513-9. [Medline].

  15. Gorden P, Gavrilova O. The clinical uses of leptin. Curr Opin Pharmacol. 2003 Dec. 3(6):655-9. [Medline].

  16. Javor ED, Cochran EK, Musso C, Young JR, Depaoli AM, Gorden P. Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. Diabetes. 2005 Jul. 54(7):1994-2002. [Medline].

  17. Oral EA, Chan JL. Rationale for leptin-replacement therapy for severe lipodystrophy. Endocr Pract. 2010 Mar-Apr. 16(2):324-33. [Medline].

  18. Rodriguez AJ, Mastronardi CA, Paz-Filho GJ. New advances in the treatment of generalized lipodystrophy: role of metreleptin. Ther Clin Risk Manag. 2015. 11:1391-400. [Medline].

  19. Bennett T, Allford M. Delayed emergence from anesthesia in a child with congenital generalized lipodystrophy (Berardinelli-Seip syndrome). Paediatr Anaesth. 2012 Mar. 22(3):299-300. [Medline].

  20. Schwartz RA. Acanthosis nigricans. J Am Acad Dermatol. 1994 Jul. 31(1):1-19; quiz 20-2. [Medline].

 
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Congenital generalized lipoatrophy in a 16-year-old girl. In T1-weighted magnetic resonance imaging (MRI) scan, transverse sections of the torso at the fifth lumbar vertebra demonstrate markedly deficient subcutaneous and visceral fat (top left). Transverse sections of the midthigh demonstrate an absence of subcutaneous fat, deep fat, intrafascicular fat, and marrow fat (bottom left); note light-colored, lipid-filled muscle tissue. Note absence of fat throughout the body (right).
 
 
 
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