Original Article Lipoprotein Lipase Deficiency: Clinical, Biochemical and Molecular Characteristics in Three Patients with Novel Mutations in the LPL Gene (lipoprotein lipase deficiency / hypertriglyceridaemia / hypercholesterolaemia / hepatosplenomegaly / acute pancreatitis / lipaemia retinalis)

Abbreviations: CM – chylomicrons, GPIHBP1 – glycosylphosphatidylinositol anchored-HDL-binding protein 1, HC – hypercholesterolaemia, HDL – high-density lipoprotein, HTG – hypertriglyceridaemia, LPL – lipoprotein lipase, MCT – medium-chain triglyceride, SNP – single-nucleotide polymorphism, TG – triglycerides, VLDL – very low-density lipoproteins. Abstract. Lipoprotein lipase (LPL) deficiency, caused by mutations in the LPL gene, is a rare autosomal recessive disorder manifesting in early childhood with recurrent abdominal pain, hepatosplenomegaly, acute pancreatitis, lipaemia retinalis and eruptive xanthomas. Typical laboratory findings are lactescent serum, extreme hypertriglyceridaemia and hypercholesterolaemia. The diagnostics is based on postheparin serum LPL assay and DNA analyses of the LPL gene. We report clinical, biochemical and molecular data of three children with LPL deficiency. One child manifested since the first week of life with recurrent abdominal pain (Patient 1), the second with abdominal distension and hepatosplenomegaly since the second month of life (Patient 3) and patient 2, asymptomatic younger brother of patient 1, was diagnosed in the first week of life. Lipaemia retinalis and splenomegaly were present in two symptomatic children, hepatomegaly in patient 3 and acute pancreatitis in patient 1. All children had lactescent serum, profound hypertriglyceridaemia (124 ± 25 mmol/l; controls < 2.2), hypercholesterolaemia (22.8 ± 7.3 mmol/l, controls < 4.2) and their LPL immunoreactive mass in serum did not increase after heparin injection. Molecular analyses revealed that both siblings are homozygous for novel mutation c.476C > G in the LPL gene changing the conserved amino acid of the catalytic centre. The third patient is a compound heterozygote for mutations c.604G>A and c.698A>G in the LPL gene, both affecting highly conserved amino acids. We conclude that LPL deficiency must be considered in neonates and young infants with abdominal pain and hypertriglyceridaemia because early treatment might prevent development of life-threatening acute pancreatitis.