Abstract 95

Homozygous mutation of AGPAT2 gene causing type 1 congenital generalized lipodystrophy

SMY Wong1, CM Mak2, YK Chong2, WM But1
Department of Paediatrics, Queen Elizabeth Hospital, Hong Kong, Hong Kong, 2Department of Pathology, Princess Margaret Hospital, Hong Kong

Introduction: Congenital generalized lipodystrophy is an extremely rare autosomal recessive disorder that is characterized by almost complete absence of adipose tissue in the body. Affected individuals are at risk of having severe metabolic complications including insulin resistance, diabetes mellitus, hypertriglyceridaemia and hepatic steatosis at young age. It can be classified into four different subtypes which are caused by mutation in different genes.

Case Report: We report a Nepalese boy who presented with prolonged jaundice and hepatosplenomegaly at one month of age. Serial blood tests found that the blood was lipaemic. His plasma triglyceride level was elevated to 3.5 mmol/L while total cholesterol level was 3.2 mmol/L. Extensive metabolic workup was performed. Upon further assessment, he had acromegaloid features with loss of fat deposition over whole body with prominent muscle bulk, protruding tongue, large penis and phlebomegaly. Subsequent USG study confirmed the paucity of subcutaneous fat in limbs. MRI abdomen showed paucity of subcutaneous and intra-abdominal fat. Echocardiogram done at 6 months of age showed mild hypertrophic cardiomyopathy. Skeletal survey was unremarkable. Genetic test detected NM_006412.3(AGPAT2):c.[676C>T];[676C>T] p.(Gln226*);(Gln226*) indicating the presence of known homozygous mutation c.676C>T (p.Gln226*) in the AGPAT2 gene and the diagnosis of type 1 congenital generalized lipodystrophy was substantiated. Both parents are carriers of this mutation. He was advised to have dietary restriction of total fat intake, limiting to 20-30% of total dietary energy intake. His hypertriglyceridaemia improved gradually. He is currently having regular monitoring for possible metabolic complication. The latest assessment done when he was 5 years of age showed he was thriving well. Besides borderline hypertriglyceridaemia 1.9 mmol/L, there were no evidences of other metabolic complications such as insulin resistance, non-alcoholic steatohepatitis and cardiomyopathy had resolved.

Learning Points: At present, there is no curative therapy for congenital generalized lipodystrophy and the goals of treatment are prevention and amelioration of associated comorbidities. It is well known that the associated metabolic complications including diabetes mellitus and extreme hypertriglyceridaemia can be resistant to traditional treatment. Therefore, early diagnosis of this condition is utmost important in preventing the development of metabolic complications. It can be done by early initiation of dietary modification with low fat diet and regular monitoring of metabolic profile. Maintaining a healthy weight and regular exercise are vital in affected individuals. New therapies such as metreleptin, which is a subcutaneous recombinant leptin analogue has been emerging and may be beneficial in improving metabolic complications associated with severe lipodystrophy.