Determination of 7-ketocholesterol in plasma by LC-MS for rapid diagnosis of acid SMase-deficient Niemann-Pick disease.

[krabbe disease]

Acid sphingomyelinase (ASMase )-deficient Niemann-Pick disease (NPD ) is caused by mutations in the sphingomyelin phosphodiesterase 1 (SMPD 1 ) gene , resulting in accumulation of sphingomyelin in the lysosomes and secondary changes in cholesterol metabolism . We hypothesized that the oxidation product of cholesterol , 7 -ketocholesterol (7 -KC ), might increase in the plasma of patients with ASMase-deficient NPD . In this study , a rapid and nonderivatized method of measurement of plasma 7 -KC by liquid chromatography-tandem mass spectrometry (LC -MS /MS ) was developed . Plasma samples from healthy subjects , patients with ASMase-deficient NPD , nonaffected ASMase-deficient NPD heterozygotes , Niemann-Pick type C (NPC ) disease , glycogen storage disorder type II (GSDII ), Gaucher disease (GD ), mucopolysaccharidosis type II (MPSII ), Krabbe disease (KD ), and metachromatic leukodystrophy (MLD ) were tested retrospectively . Markedly elevated 7 -KC was found in patients with ASMase-deficient NPD and NPC disease that showed significant differences from ASMase-deficient NPD heterozygotes ; patients with GSDII , GD , MPSII , KD , and MLD ; and normal controls . The analysis of plasma 7 -KC by LC -MS /MS offers the first simple , quantitative , and highly sensitive method for detection of ASMase-deficient NPD and could be useful in the diagnosis of both ASMase-deficient NPD and NPC disease .

Diseases
Validation

Diseases presenting "leukodystrophy" symptom

achondroplasia

adrenomyeloneuropathy

alexander disease

cadasil

canavan disease

carcinoma of the gallbladder

classical phenylketonuria

coats disease

fabry disease

gm1 gangliosidosis

krabbe disease

neonatal adrenoleukodystrophy

phenylketonuria

pyruvate dehydrogenase deficiency

wiskott-aldrich syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

This symptom has already been validated