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CASE REPORT
Year : 2017  |  Volume : 18  |  Issue : 3  |  Page : 227-229

Congenital generalized lipodystrophy in children: Berardinelli–Seip syndrome – two rare cases with renal manifestations


1 Department of DVL, G.S.L. Medical College, Rajahmundry, Andhra Pradesh, India
2 Surya Skin Care and Research Center, Visakhapatnam, Andhra Pradesh, India

Date of Web Publication7-Jun-2017

Correspondence Address:
Gandikota Raghu Rama Rao
Department of DVL, G.S.L. Medical College, Rajanagaram, Rajahmundry - 533 296, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2319-7250.193008

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  Abstract 

Berardinelli–Seip syndrome is a rare autosomal recessive disorder characterized by an almost total lack of subcutaneous fat with various metabolic abnormalities and complications such as diabetes mellitus and insulin resistance. Renal changes and complications are uncommon but reported. We present two such rare cases with renal involvement.

Keywords: Acanthosis nigricans, Berardinelli–Seip syndrome, congenital generalized lipodystrophy, hypertrichosis, renal changes


How to cite this article:
Satya S, Rama Rao GR, Prathima K, Lavanya D, Sandeep K, Amareswar A. Congenital generalized lipodystrophy in children: Berardinelli–Seip syndrome – two rare cases with renal manifestations. Indian J Paediatr Dermatol 2017;18:227-9

How to cite this URL:
Satya S, Rama Rao GR, Prathima K, Lavanya D, Sandeep K, Amareswar A. Congenital generalized lipodystrophy in children: Berardinelli–Seip syndrome – two rare cases with renal manifestations. Indian J Paediatr Dermatol [serial online] 2017 [cited 2017 Sep 26];18:227-9. Available from: http://www.ijpd.in/text.asp?2017/18/3/227/193008


  Introduction Top


Congenital generalized lipodystrophy is a rare autosomal recessive disorder characterized by the absence of adipose tissue and insulin resistance.[1] It was first described by Berardinelli in 1954 in Brazil and further characterized by Seip and Trygstad [2] and was subsequently named as Berardinelli–Seip congenital lipodystrophy (BSCL). On the basis of the mutational and haplotype analysis, BSCL families have been classified into three types BSCL1, BSCL2, and BSCLX.[3] The prevalence is <1 in 10 million population and approximately 250 cases have been reported in various ethnic groups.[4],[5],[6] The main clinical and metabolic features are generalized lipoatrophy, muscle hypertrophy, hepatomegaly, insulin resistance, acanthosis nigricans, psychomotor and mental retardation, hypertrichosis/hirsutism, acromegaly, hyperinsulinemia, and hypertriglyceridemia.[1],[3] Renal involvement is uncommon but reported.[7],[8] Considering the rarity of this syndrome and renal manifestations, we report these two cases.


  Case Reports Top


Case 1

A 13-month-old female child, born out of nonconsanguineous marriage, was brought to our department with complaints of abnormal facial features, almost complete generalized absence of subcutaneous fat, muscular hypertrophy, generalized hypertrichosis, and progressively increasing abdominal size, since 4 months of her age. Family history was not significant. No delayed milestones were observed. She also had a voracious appetite. On examination, the child had abundant thick scalp hair, acromegaloid face with hypertrophied muscles, giving an athletic appearance. In addition, acanthosis nigricans, enlargement of both breasts (Tanner Stage 3) and clitoromegaly were found [Figure 1] and [Figure 2]. Her height was 84 cm, weight 8 kg (above 98 percentile of the WHO growth chart). On systemic examination, there was an umbilical hernia with hepatomegaly and no other abnormality was seen. All relevant hematological, biochemical, and immunological parameters were within normal limits except hemoglobin - 6.2 g%, alkaline phosphatase - 323 IU/L, and triglycerides - 412 mg/dl. Renal parameters such as serum creatinine, blood urea, and 24 h urine protein excretion were within normal limits. Microalbuminuria was not detected. Ultrasound abdomen showed mild hepatomegaly and Grade II renal parenchymal changes. Radiological examination of long bones, pelvis, and computed tomography (CT) brain were normal. Electrocardiograph (ECG) and echocardiogram were also normal.
Figure 1: A 13-month-old baby with abundant scalp hair and hypertrichosis and lipodystrophy of cheeks

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Figure 2: clitoromegaly

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Case 2

An 11-year-old male, born out of second degree consanguineous marriage, presented with hyperpigmentation and thickening of flexural areas and generalized hypertrichosis since birth. His parents noticed the loss of fat over both cheeks from 1 year of age and masculine features with muscular hypertrophy by the age of 10 years. Other siblings were normal. On examination, acanthosis nigricans over the neck and axillae, acromegaloid features with abundant scalp hair were present [Figure 3] and [Figure 4]. Systemic examination was normal. All relevant hematological, biochemical, and immunological parameters were within normal limits. Renal parameters such as serum creatinine, blood urea, and 24 h urine protein excretion were within normal limits. Microalbuminuria was not detected. Ultrasound abdomen showed mild hepatomegaly and Grade I and II renal parenchymal changes. Radiological examination of long bones, pelvis, and CT brain were normal. ECG and echocardiogram were also normal.
Figure 3: An 11-year-old boy with acanthosis nigricans and lipodystrophy of cheeks

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Figure 4: Acanthosis nigricans and hypertrichosis

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  Discussion Top


Lipodystrophies represent a heterogeneous group of diseases, characterized by generalized or partial alteration in the body fat development/distribution and insulin resistance. The other cardinal signs are acanthosis nigricans, hypertrichosis, and muscle hypertrophy. Lipodystrophies are also classified as congenital and acquired.[1],[3] Congenital lipodystrophy or Berardinelli–Seip syndrome is transmitted as an autosomal recessive trait on two genetic loci on chromosome 9q34 and 11q13.[3],[9] Leptin (fat-derived hormone) deficiency and absence of adipose tissue are the main determinants of metabolic abnormalities in this condition.[10] Because of the absence of functional adipocytes, lipid is stored in other tissues including liver and muscle. Hepatomegaly, observed since childhood, is caused by steatosis. Major diagnostic criteria are lipodystrophy affecting both trunk and limbs, giving an athletic appearance, acromegaloid features, hepatomegaly, elevated triglycerides, and insulin resistance (acanthosis nigricans). The minor criteria are hypertrophic cardiomyopathy, mental retardation, hypertrichosis/hirsutism, precocious puberty in females, and bone cyst.[2],[3] Both of our patients fulfilled all major criteria and one minor criterion (hypertrichosis), but both were having normal glucose levels. Lipoatrophy and hypertrichosis were obvious from birth in both cases. In the case of female patient, triglycerides were remarkably elevated, may be, leading to hepatomegaly and raised alkaline phosphatase. In addition to above metabolic abnormalities, Javor et al. reported renal involvement such as proteinuria, microalbuminuria, and elevated creatinine clearance. They also reported focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, and diabetic nephropathy and treated them with recombinant leptin.[7] Both of our index cases also showed renal parenchymal changes of Grade I and II in ultrasound with normal renal parameters. Regular follow-up is necessary for all these cases because renal failure is the common cause of death, apart from gastrointestinal hemorrhage due to liver failure.[3],[7] Some patients may also develop cirrhosis in adult life. The carbohydrate metabolic abnormality is characterized by peripheral insulin resistance associated with hyperinsulinemia resulting in diabetes mellitus.[1],[3] Although fasting blood sugar levels were normal in our two cases, dominant acanthosis nigricans is suggestive of insulin resistance. Diabetes mellitus is late onset in cases of lipodystrophy. Cardiac abnormalities including ventricular dysfunction and hypertrophic cardiomyopathy were also reported.[1],[3]

Early detection and multidisciplinary approach would prevent metabolic complications in these cases. They should consume a low-fat diet with reduction of saturated and trans fat intake along with the daily physical activity. Leptin, a novel option for therapy, may improve insulin resistance, hyperglycemia, dyslipidemia, and hepatic steatosis.[6],[10]

Declaration of Patient Consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/ her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.

 
  References Top

1.
Handelsman Y, Oral EA, Bloomgarden ZT, Brown RJ, Chan JL, Einhorn D, et al. The clinical approach to the detection of lipodystrophy – An AACE consensus statement. Endocr Pract 2013;19:107-16.  Back to cited text no. 1
    
2.
Seip M, Trygstad O. Generalized lipodystrophy. Arch Dis Child 1963;38:447-53.  Back to cited text no. 2
    
3.
Van Maldergem L. Berardinelli-Seip congenital lipodystrophy. Orphanet encyclopedia. 2001. Available from: http://www.orpha.net/data/patho/GB/uk-berard.pdf. [Last accessed on 2001 Nov].  Back to cited text no. 3
    
4.
Khandpur S, Kumar A, Khadgawat R. Congenital generalized lipodystrophy of Berardinelli-Seip type: A rare case. Indian J Dermatol Venereol Leprol 2011;77:402.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Metwalley KA, Farghaly HS. Berardinelli-Seip syndrome type 1 in an Egyptian child. Indian J Hum Genet 2014;20:75-8.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Babu P, Sharma R, Jayaseelan E, Appachu D. Berardinelli-Seip syndrome in a 6-year-old boy. Indian J Dermatol Venereol Leprol 2008;74:644-6.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Javor ED, Moran SA, Young JR, Cochran EK, DePaoli AM, Oral EA, et al. Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: Baseline characteristics and course during recombinant leptin therapy. J Clin Endocrinol Metab 2004;89:3199-207.  Back to cited text no. 7
    
8.
Gürakan F, Koçak N, Yüce A. Congenital generalized lipodystrophy: Berardinelli syndrome. Report of two siblings. Turk J Pediatr 1995;37:241-6.  Back to cited text no. 8
    
9.
Garg A. Acquired and inherited lipodystrophies. N Engl J Med 2004;48:1433-44.  Back to cited text no. 9
    
10.
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;53:513-9.  Back to cited text no. 10
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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