Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Norum-Krankheit

Die Norum-Krankheit ist eine autosomal rezessive Erkrankung die auf Mutationen des LCAT-Gens beruht. Die Erkrankung ist durch Hornhauttrübung, normochrome hämolytische Anämie und Schaumzellen im Knochenmark charakterisiert. Zu den typischen Laborbefunden zählen rhöhte Triglycerid-, Phospholipid und Cholestrolspiegel. Auch eine Proteinurie kann gefunden werden.

Pathogenese

Biochemisch ist diese Erkrankung durch einen kompletten Ausfall des Enzyms Lecithin-cholesterol acyltransferase (LCAT) gekennzeichnet. Das betrifft sowohl die Funktion an den kleinen HDL-Partikeln, wo das ApoA1 der den Enzymaktivator bildet, wie auch an den großen ApoB-enthaltenden Lipoproteinen.

Management

Die Therapie besteht in einer cholestrinarmen Diät und ggf. Bluttransfusionen zum Ausgleich der Anämie. Eine kausale Therapie ist mit der Lebertransplantation möglich.

Gliederung

Glomerulosklerose
Familiäre partielle Lipodystrophie Typ 2
Fokal segmentale Glomerulosklerose (FSGS)
Frasier-Syndrom
Glycogenspeicherkrankheit 1A
Norum-Krankheit
LCAT

Referenzen:

1.

Gotoda T et al. (1991) Differential phenotypic expression by three mutant alleles in familial lecithin:cholesterol acyltransferase deficiency.

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2.

Taramelli R et al. (1990) Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele.

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3.

Humphries SE et al. (1988) A study of the structure of the gene for lecithin: cholesterol acyltransferase in four unrelated individuals with familial lecithin: cholesterol acyltransferase deficiency.

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4.

Norum KR et al. (1974) Lecithin: cholesterol acyltransferase recent research on biochemistry and physiology of the enzyme.

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5.

Norum KR et al. (1967) Familial serum-cholesterol esterification failure. A new inborn error of metabolism.

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6.

Vergani C et al. (1983) A new case of familial LCAT deficiency.

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7.

Teisberg P et al. (1975) Genetics of LCAT (lecithin: cholesterol acyltransferase) deficiency.

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8.

Frohlich J et al. (1982) Detection of heterozygotes for familial lecithin: cholesterol acyltransferase (LCAT) deficiency.

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9.

Weber P et al. (1987) Hereditary lecithin-cholesterol acyltransferase deficiency. Case report of a German patient.

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10.

Flatmark AL et al. (1977) Renal transplantation in patients with familial lecithin: cholesterol-acetyltransferase deficiency.

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11.

Teisberg P et al. (1974) Probable linkage of LCAT locus in man to the alpha haptoglobin locus on chromosome 16.

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12.

Nordöy A et al. (1971) Familial plasma lecithin: cholesterol acyltransferase deficiency. A study of the platelets.

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13.

Gjone E et al. () Familial serum cholesterol ester deficiency. Clinical study of a patient with a new syndrome.

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14.

Gjone E et al. (1968) Familial plasma cholesterol ester deficiency. A study of the erythrocytes.

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15.

Murayama N et al. (1984) Decreased sodium influx and abnormal red cell membrane lipids in a patient with familial plasma lecithin: cholesterol acyltransferase deficiency.

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16.

Teisberg P et al. (1981) Genetic heterogeneity in familial lecithin:cholesterol acyltransferase (LCAT) deficiency.

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17.

Sakuma M et al. (1982) Familial plasma lecithin: cholesterol acyltransferase deficiency. A new family with partial LCAT activity.

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18.

Albers JJ et al. (1982) Familial lecithin-cholesterol acyltransferase deficiency in a Japanese family: evidence for functionally defective enzyme in homozygotes and obligate heterozygotes.

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19.

Borysiewicz LK et al. (1982) Renal failure in familial lecithin: cholesterol acyltransferase deficiency.

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20.

Gjone E et al. (1981) Familial lecithin:cholesterol acyltransferase deficiency. Report of a fourth family from northwestern Norway.

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21.

Albers JJ et al. (1981) Genetic control of lecithin-cholesterol acyltransferase (LCAT): measurement of LCAT mass in a large kindred with LCAT deficiency.

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22.

Utermann G et al. (1981) Lecithin-cholesterol-acyltransferase deficiency: autosomal recessive transmission in a large kindred.

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23.

Albers JJ et al. (1981) Familial lecithin-cholesterol acyltransferase: identification of heterozygotes with half-normal enzyme activity and mass.

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24.

Rader DJ et al. (1994) Markedly accelerated catabolism of apolipoprotein A-II (ApoA-II) and high density lipoproteins containing ApoA-II in classic lecithin: cholesterol acyltransferase deficiency and fish-eye disease.

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25.

Hoeg JM et al. (1996) Overexpression of lecithin:cholesterol acyltransferase in transgenic rabbits prevents diet-induced atherosclerosis.

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26.

Sakai N et al. (1997) Targeted disruption of the mouse lecithin:cholesterol acyltransferase (LCAT) gene. Generation of a new animal model for human LCAT deficiency.

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27.

Ng DS et al. (1997) Disruption of the murine lecithin:cholesterol acyltransferase gene causes impairment of adrenal lipid delivery and up-regulation of scavenger receptor class B type I.

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28.

Muthusethupathi MA et al. (1999) Familial Lecithin:cholesterol acyltransferase deficiency with renal failure in two siblings. First case report from India.

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