Familial chylomicronemia syndrome
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《美国医学杂志》
1 Departments of Ophthalmology, Medical College, Thiruvananthapuram, Kerala, India
2 Departments of Pediatrics, Medical College, Thiruvananthapuram, Kerala, India
Abstract
Familial chylomicronemia syndrome is a group of rare genetic disorders characterized by deficient activity of an enzyme lipoprotein lipase or apo-protein C-II deficiency. Incidence is 1 out of 1,000,000. Alternative names to this syndrome are Type I hyper lipoproteinemia and familial lipoprotein lipase deficiency.
Keywords: Chylomicrons; Lipoproteinemia; Lipemia retinalis
A defective gene is usually the cause of this disorder, which is inherited in an autosomal recessive manner. The disease is a result of mutation in either the lipoprotein lipase gene or the apo-protein C-II gene which codes for an essential co-factor resulting in functional inability to hydrolyse triglycerides in chylomicrons and consequent build up of fat laden chylomicrons in blood. To date, over 80 mutations in the LpL gene have been reported.[1] Patients with lipoprotein lipase deficiency usually present with chylomicronemia in childhood.[2] Parents will have normal triglycerides level & there is no family history of severe hyper lipidemia. Blood tests show a high level of chylomicrons, a lipoprotein that carries fats from digested food into the blood stream.[3]
The authors describe an infant who presented with all the features of familial chylomicronemia.
Case report
Fifty two days (52 days) old, term girl baby born out of non consanguinous marriage with a birth weight of 2 kgs with uneventful antenatal, natal and post natal periods presented to us with dark greenish coloured stools and excessive cry for 2 days. The child was on exclusive breast-feeding since birth. Weight gain was adequate (present weight 4.5 kg). Development, hearing and vision were normal for her age. The child was admitted in the ward with the clinical diagnosis of sepsis.
A physical examination of the child revealed an enlarged liver, an enlarged spleen and few papular lesions over face.
Blood examination showed milky appearing plasma, with a cake of chylomicrons over the surface on overnight refrigeration. A lipid profile showed a blood triglycerides level of more than 8360 mg/dl and blood cholesterol level > 1690 mg/dl. Lipid profile of parents and the sibling were normal.
Lipoprotein electrophoresis demonstrated a band of chylomicrons. An eye examination of the child revealed a pale retina and whitish retinal vessels. Lipoprotein lipase and Apo C-II deficiency has not been performed, which can be done only in specialized lipid centers. The child was managed symptomatically. Fresh frozen plasma was given to lower blood triglycerides level and the child was advised to continue breastfeeding.
Discussion
Familial chylomicronemia syndrome (type 1 hyperlipoproteinemia), a rare autosomal recessive trait affecting 1/1million population.[4] Clinically this condition can be silent and discovered incidentally owing to the lipemic appearance of the blood.[3]
Familial lipoprotein lipase deficiency usually presents in childhood with episodes of abdominal pain , recurrent pancreatitis, eruptive cutaneous xanthomas, hepato splenomegaly (due to ingestion of chylomicrons by the reticuloendothelial system) and lipemia retinalis(a pale appearance to the retinal veins).[5] The disease affects both sexes equally. About 25% of patients develop symptoms before the age of one year and the majority develop symptoms before the age of ten years.[5] Diagnosis is based on clinical presentation, lactescent plasma, forming cake of chylomicrons on overnight refrigeration, blood triglycerides >1000 mg/dl, with elevated total cholesterol, lipoprotein electrophoresis[6] demonstrating the markedly elevated chylomicrons and a special test showing deficient lipoprotein lipase activity in blood collected after treatment with IV heparin.[3]
Familial lipoprotein lipase deficiency is inherited in an autosomal recessive manner. The sibs of an affected individual have a 25% chance of being affected, a 50% chance of being unaffected and carriers, and a 25% chance of being unaffected and not carriers. The offsprings of an individual with familial lipoprotein lipase deficiency are obligate heterozygotes (carriers) for a disease causing mutation in the LPL gene. The parents of an affected individual are obligate heterozygotes and, therefore, carry a single copy of a disease causing mutation in the LPL gene.[5]
The index case had a blood triglycerides level of 8360 mg/dl and blood cholesterol of 1690 mg/dl. There was no family history of severe hyperlipidemia. The lipid profile of parents and sibling was normal.
Treatment is intended to control the symptoms and elevated blood triglycerides levels with a very low fat diet. Fresh frozen plasma is given to provide exogenous source of apo.C-II. Dietary therapy with fat-soluble vitamins and calorie supplementation with MCT (coconut oil) were successful in supporting the effectiveness of this therapeutic approach.[7] Dietary counseling of the patient and genetic counseling for the family were recommended. The index case was being treated similarly and the child was advised for follow-up in OPD.
It is important to explain to the child and parents that hypercholesterolemia in childhood is only a risk factor and not an illness. Premature atherosclerosis can occur in patients with familial chylomicronemia as a result of mutations in the lipoprotein lipase gene.[2] By following a very low fat diet a child may live into adulthood. There is no known prevention for this rare inherited disorder. Prompt institution of a very low fat diet can dramatically improve the symptoms of this disorder. Prenatal testing may be available for families in which the disease causing mutations have been identified in an affected family member.[5]
References
1. Evans D, Wendt D, Ahle S, Guerra A, Beisiegel U. Compound heterozygosity for a new (S259G) and a previously described (G188E) mutation in lipoprotein lipase (LpL) as acause of chylomicronemia. Mutations in brief no. 183. Online. Hum Mutat 1998; 12 (3): 217.
2. Benlian P, De Gennes JL, Foubert L, Zhang H, Gagne SE, Hayden M. Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene. N Engl J Med 1997; 336 (14): 1026-1027
3. Andrew M, Tershakovec, Daniel J Rader. Disorders of Lipoprotein Metabolism and Transport. In Behrman R E, Kliegman R M, Jensor HB, eds. Nelson Textbook of Pediatrics 17th edn. Philadelphia, W. B. Saunders Company, 2004; 456.
4. Reina M, Brunzell JD, Deeb SS. Molecular basis of familial chylomicronemia: mutations in the lipoprotein lipase and apolipoprotein C- II genes. J Lipid Res 1992; 33 (12): 1823-1832.
5. John D Brunzell. Familial Chylomicronemia and genetics. April2004. Familial Lipoprotein Lipase Deficiency (Familial LPL deficiency, Type I Hyperlipoproteinemia).Available from: URL:http://www.geneclinics.org/servlet /acess / Accessed on June 30, 2004.
6. Rifai N, Bachorik P S,Albers J J. Lipids, Lipoproteins and Apolipoproteins. In: TIETZ Text book of clinical chemistry, 3rd edn. Eds. Burtis CA, Ashwood ER. Singapore, WB Saunders Company, 1999; 851-852.
7. Kavazarakis E, Stabouli S, Gourgiotis D, roumeliotou K, Traeger-Synodinos J, Bossios A, Fretzayas A, Kanavakis E. Severe hypertriglyceridaemia in a Greek infant: a clinical, biochemical and genetic study. Eur J Pediatr 2004; 163(8):462. Publisheed online: 5 Jun 2004.(Mohandas MK, Jemila J, Aj)
2 Departments of Pediatrics, Medical College, Thiruvananthapuram, Kerala, India
Abstract
Familial chylomicronemia syndrome is a group of rare genetic disorders characterized by deficient activity of an enzyme lipoprotein lipase or apo-protein C-II deficiency. Incidence is 1 out of 1,000,000. Alternative names to this syndrome are Type I hyper lipoproteinemia and familial lipoprotein lipase deficiency.
Keywords: Chylomicrons; Lipoproteinemia; Lipemia retinalis
A defective gene is usually the cause of this disorder, which is inherited in an autosomal recessive manner. The disease is a result of mutation in either the lipoprotein lipase gene or the apo-protein C-II gene which codes for an essential co-factor resulting in functional inability to hydrolyse triglycerides in chylomicrons and consequent build up of fat laden chylomicrons in blood. To date, over 80 mutations in the LpL gene have been reported.[1] Patients with lipoprotein lipase deficiency usually present with chylomicronemia in childhood.[2] Parents will have normal triglycerides level & there is no family history of severe hyper lipidemia. Blood tests show a high level of chylomicrons, a lipoprotein that carries fats from digested food into the blood stream.[3]
The authors describe an infant who presented with all the features of familial chylomicronemia.
Case report
Fifty two days (52 days) old, term girl baby born out of non consanguinous marriage with a birth weight of 2 kgs with uneventful antenatal, natal and post natal periods presented to us with dark greenish coloured stools and excessive cry for 2 days. The child was on exclusive breast-feeding since birth. Weight gain was adequate (present weight 4.5 kg). Development, hearing and vision were normal for her age. The child was admitted in the ward with the clinical diagnosis of sepsis.
A physical examination of the child revealed an enlarged liver, an enlarged spleen and few papular lesions over face.
Blood examination showed milky appearing plasma, with a cake of chylomicrons over the surface on overnight refrigeration. A lipid profile showed a blood triglycerides level of more than 8360 mg/dl and blood cholesterol level > 1690 mg/dl. Lipid profile of parents and the sibling were normal.
Lipoprotein electrophoresis demonstrated a band of chylomicrons. An eye examination of the child revealed a pale retina and whitish retinal vessels. Lipoprotein lipase and Apo C-II deficiency has not been performed, which can be done only in specialized lipid centers. The child was managed symptomatically. Fresh frozen plasma was given to lower blood triglycerides level and the child was advised to continue breastfeeding.
Discussion
Familial chylomicronemia syndrome (type 1 hyperlipoproteinemia), a rare autosomal recessive trait affecting 1/1million population.[4] Clinically this condition can be silent and discovered incidentally owing to the lipemic appearance of the blood.[3]
Familial lipoprotein lipase deficiency usually presents in childhood with episodes of abdominal pain , recurrent pancreatitis, eruptive cutaneous xanthomas, hepato splenomegaly (due to ingestion of chylomicrons by the reticuloendothelial system) and lipemia retinalis(a pale appearance to the retinal veins).[5] The disease affects both sexes equally. About 25% of patients develop symptoms before the age of one year and the majority develop symptoms before the age of ten years.[5] Diagnosis is based on clinical presentation, lactescent plasma, forming cake of chylomicrons on overnight refrigeration, blood triglycerides >1000 mg/dl, with elevated total cholesterol, lipoprotein electrophoresis[6] demonstrating the markedly elevated chylomicrons and a special test showing deficient lipoprotein lipase activity in blood collected after treatment with IV heparin.[3]
Familial lipoprotein lipase deficiency is inherited in an autosomal recessive manner. The sibs of an affected individual have a 25% chance of being affected, a 50% chance of being unaffected and carriers, and a 25% chance of being unaffected and not carriers. The offsprings of an individual with familial lipoprotein lipase deficiency are obligate heterozygotes (carriers) for a disease causing mutation in the LPL gene. The parents of an affected individual are obligate heterozygotes and, therefore, carry a single copy of a disease causing mutation in the LPL gene.[5]
The index case had a blood triglycerides level of 8360 mg/dl and blood cholesterol of 1690 mg/dl. There was no family history of severe hyperlipidemia. The lipid profile of parents and sibling was normal.
Treatment is intended to control the symptoms and elevated blood triglycerides levels with a very low fat diet. Fresh frozen plasma is given to provide exogenous source of apo.C-II. Dietary therapy with fat-soluble vitamins and calorie supplementation with MCT (coconut oil) were successful in supporting the effectiveness of this therapeutic approach.[7] Dietary counseling of the patient and genetic counseling for the family were recommended. The index case was being treated similarly and the child was advised for follow-up in OPD.
It is important to explain to the child and parents that hypercholesterolemia in childhood is only a risk factor and not an illness. Premature atherosclerosis can occur in patients with familial chylomicronemia as a result of mutations in the lipoprotein lipase gene.[2] By following a very low fat diet a child may live into adulthood. There is no known prevention for this rare inherited disorder. Prompt institution of a very low fat diet can dramatically improve the symptoms of this disorder. Prenatal testing may be available for families in which the disease causing mutations have been identified in an affected family member.[5]
References
1. Evans D, Wendt D, Ahle S, Guerra A, Beisiegel U. Compound heterozygosity for a new (S259G) and a previously described (G188E) mutation in lipoprotein lipase (LpL) as acause of chylomicronemia. Mutations in brief no. 183. Online. Hum Mutat 1998; 12 (3): 217.
2. Benlian P, De Gennes JL, Foubert L, Zhang H, Gagne SE, Hayden M. Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene. N Engl J Med 1997; 336 (14): 1026-1027
3. Andrew M, Tershakovec, Daniel J Rader. Disorders of Lipoprotein Metabolism and Transport. In Behrman R E, Kliegman R M, Jensor HB, eds. Nelson Textbook of Pediatrics 17th edn. Philadelphia, W. B. Saunders Company, 2004; 456.
4. Reina M, Brunzell JD, Deeb SS. Molecular basis of familial chylomicronemia: mutations in the lipoprotein lipase and apolipoprotein C- II genes. J Lipid Res 1992; 33 (12): 1823-1832.
5. John D Brunzell. Familial Chylomicronemia and genetics. April2004. Familial Lipoprotein Lipase Deficiency (Familial LPL deficiency, Type I Hyperlipoproteinemia).Available from: URL:http://www.geneclinics.org/servlet /acess / Accessed on June 30, 2004.
6. Rifai N, Bachorik P S,Albers J J. Lipids, Lipoproteins and Apolipoproteins. In: TIETZ Text book of clinical chemistry, 3rd edn. Eds. Burtis CA, Ashwood ER. Singapore, WB Saunders Company, 1999; 851-852.
7. Kavazarakis E, Stabouli S, Gourgiotis D, roumeliotou K, Traeger-Synodinos J, Bossios A, Fretzayas A, Kanavakis E. Severe hypertriglyceridaemia in a Greek infant: a clinical, biochemical and genetic study. Eur J Pediatr 2004; 163(8):462. Publisheed online: 5 Jun 2004.(Mohandas MK, Jemila J, Aj)