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Novel subtype of congenital generalized lipodystrophy associated with muscular weakness and cervical spine instability
Author(s) -
Simha Vinaya,
Agarwal Anil K.,
Aronin Patricia A.,
Iannaccone Susan T.,
Garg Abhimanyu
Publication year - 2008
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32457
Subject(s) - medicine , weakness , cervical spine , physical medicine and rehabilitation , spine (molecular biology) , proximal muscle weakness , pediatrics , anatomy , surgery , biology , bioinformatics , muscle biopsy , biopsy
Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by extreme paucity of adipose tissue from birth, and early onset of metabolic complications related to insulin resistance. Mutations in three genes, 1‐acylglycerol 3‐phosphate‐ O ‐acyltransferase 2 ( AGPAT2 ), Berardinelli Seip Congenital Lipodystrophy 2 ( BSCL2 ), and Caveolin‐1 ( CAV1 ) are associated with the three subtypes of this disorder, CGL1, CGL2 and CGL3, respectively. We report two siblings of Hispanic origin who displayed characteristic features of CGL such as generalized loss of subcutaneous fat from birth, acanthosis nigricans, acromegaloid habitus, umbilical prominence, hepatosplenomegaly, hypoleptinemia, dyslipidemia, and insulin resistance. However, no disease causing variants were detected in the DNA sequence of AGPAT2 , BSCL2 or CAV1 genes. Further, whole body magnetic resonance imaging (MRI) in the two siblings revealed marked loss of subcutaneous, intraabdominal and intrathoracic fat like in other patients with CGL, but preservation of bone marrow fat which is invariably lost in all patients with CGL1 and CGL2, but not in the patient reported with CGL3. They also had generalized muscle weakness during infancy and early childhood associated with a nearly fivefold increase in serum creatine kinase (CK) levels, but with normal muscle biopsy and electrophysiologic studies. Both patients were also found to have atlantoaxial dislocation requiring surgical intervention. Thus, this pedigree represents a novel subtype of CGL characterized by generalized loss of body fat but with preservation of bone marrow fat, congenital muscular weakness and cervical spine instability. The genetic basis of this novel subtype remains to be determined. © 2008 Wiley‐Liss, Inc.