Vishal V Tewari1*, Ritu Mehta2 and Kunal Tewari3
1Department of Pediatrics, Army Hospital (Referral & Research), New Delhi, India
2Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
3Department of Anaesthesia, Base Hospital, New Delhi, India
Received: 08 February, 2016; Accepted: 20 April, 2016; Published: 21 April, 2016
Dr, Vishal V Tewari, MD (Pediatrics), DNB (Neonatology), MNAMS, Department of Pediatrics, Army Hospital (Referral & Research), NewDelhi-110010, India, Tel: +91-8826118889; E-mail:
Tewari VV, Mehta R, Tewari K (2016) Congenital Generalized Lipodystrophy: A Multisystemic Metabolic Disorder. Int J Clin Endocrinol Metab 2(1): 005-007.
© 2016 Tewari VV, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Congenital generalised lipodystrophy; Acanthosis nigricans; Lipoatrophic diabetes
AGPAT: Acylglycerol-Phosphate-Acyltransferase; BMR: Basal Metabolic Rate, BSCL: Berardinelli-Seip Congenital Lipodystrophy, GH: Growth Hormone; SMR: Sexual Maturity Rating; US:LS: Upper Segment to Lower Segment ratio;
Introduction: Congenital generalized lipodystrophy or Berardinelli-Seip syndrome is a rare autosomal recessive multisystem disorder characterized by the near absence of subcutaneous and visceral adipose tissue from birth or early infancy with severe insulin resistance. It is caused by mutations in the gene for AGPAT-2 on chromosome 9 or BSCL-2/Seipin on chromosome 11 resulting in triglyceride-depleted adipocytes. BSCL-2/Seipin is a cell autonomous regulator of lipolysis essential for adipocyte differentiation.
Case: A 6-year-old male child presented with abdominal distention. He was noted to have a characteristic phenotype with generalizRed absence of subcutaneous fat over the body with acanthosis nigricans and hepatomegaly. His anthropometric indices were above the 75th centile for age and he was in sexual maturity rating Stage II. Investigations revealed hyperglycemia, hypercholesterolemia with fatty infiltration of liver and hyperinsulinemia with normal Growth hormone levels and accelerated bone age. The clinical features, pathogenesis, management and prognosis are discussed.
Conclusion: Congenital generalized lipodystrophy is an exceptionally rare disorder with prevalence of 1 per 12 million population, affecting all ethnic groups. It is characterized by generalized lipodystrophy, acanthosis nigricans, prominent superficial veins, muscle hypertrophy, hirsuitism, accelerated skeletal growth with tall stature and genital precocity. Metabolic derangements seen are hyperlipidemia, hepatomegaly and non-ketotic insulin resistant diabetes mellitus. Death occurs in the third decade due to complications of diabetes, cardiomyopathy or cirrhosis. Our case showed all the phenotypic and metabolic features of this syndrome with early appearance of and difficult to control diabetes mellitus.
Loss of fatty tissue occurring in a partial or generalized distribution is called as lipodystrophy. Generalized lipodystrophy may be congenital or acquired in nature. Congenital generalized lipodystrophy or Berardinelli-Seip syndrome is a rare autosomal recessive multisystem disorder characterized by the near absence of subcutaneous and visceral adipose tissue from birth or early infancy with severe insulin resistance. Other clinical and biological features include a specific phenotype, cutaneous changes, and an anabolic syndrome with metabolic derangements. Findings seen less commonly include xanthomas, cardiac hypertrophy, hypertension, enlargement of parotid glands, ovarian cysts and clitoromegaly in females . Difficult to control brittle diabetes mellitus may present by the end of second decade. Herein we present a 6 year old child who showed all the phenotypic and metabolic features of this syndrome with early appearance of and difficult to control diabetes mellitus.
A 6-year-old male child, second sib of a second-degree consanguineous marriage presented with progressive abdominal distention. There was history of the child having thin limbs and an emaciated look on the face during infancy. Child had a triangular face with loss of the buccal fat pad giving the face a gaunt appearance. His weight was 25 kg (> 90th centile), height was 120.5 cm (>75th centile), weight for height was between 75th to 90th centile with Upper segment to Lower segment (US:LS) ratio of 1.3: 1.0. There was generalized loss of subcutaneous fat over the limbs and the trunk, with hypertrophied limb muscles and prominent veins (Figure 1). Acanthosis nigricans was seen in both axillae and groins. His scalp hair was thick and curly and child was in sexual maturity rating (SMR) stage II. He had a 5 cm non-tender firm hepatomegaly and no splenomegaly. His neurological examination was normal with normal intellectual faculties. Investigations revealed a normal hemogram and urine exam positive for reducing substance. His fasting blood sugar value was 226 mg/dl, and the post-prandial value was 327 mg/dl. Serum cholesterol was 370 mg/dl with Serum Triglycerides of 190 mg/dl. All other biochemical parameters were normal. X-ray of left wrist and hand corresponded with a bone age of 9-10 years. Ultrasound abdomen showed hepatomegaly with fatty infiltration of liver. Echocardiography did not reveal any cardiomyopathy. The fasting plasma Insulin assay showed hyperinsulinemia and was 33 uU/ml (Normal 7-24 uU/ml). A Growth hormone (GH) assay was done following IV administration of 0.1 IU/kg of Plain Insulin, on samples collected at 30 and 60 minutes following the dose. Both samples had normal GH levels (< 10 mcg/L). Plasma Leptin assay and genetic analysis was not done due to resource limitation. The child was diagnosed as a case of congenital generalized lipodystrophy Type 1 and started on Insulin therapy with Human Insulin at 2 Units/kg SC in 2 divided doses and oral Atorvastatin 10 mg once daily. Dietary therapy with high fiber, low fat diet and small meals was advised. The proportions of easily digestible and simple carbohydrates were kept lesser. Topical retinoids (0.025% Isotretenoin) were prescribed for the acanthosis nigricans. The child is on regular follow-up and continues to show accelerated growth, precocity and severe insulin resistance. On therapy his blood sugar and lipid profile are within acceptable limits for age and close tracking of blood pressure for hypertension is being done.
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