The usefulness of bone marrow aspiration in the diagnosis of Niemann-Pick disease type C in infantile liver disease
ABSTRACT Niemann-Pick disease type C (NPC) is a fatal, autosomal recessive lysosomal storage disease which may present in infancy with cholestatic jaundice and/or hepatosplenomegaly. In cholestatic patients with splenomegaly, a bone marrow aspirate has been advocated as a relatively accessible tissue to demonstrate storage phenomena. Typically in patients with NPC, macrophages with abnormal cholesterol storage, so called foam cells, can be detected in the bone marrow.
To review our experience of bone marrow aspiration in children with NPC presenting with infantile liver disease.
A retrospective analysis of 11 consecutive children (8 males) from Birmingham Children's Hospital with NPC presenting with infantile liver disease was undertaken. The diagnosis of NPC was confirmed in all cases by demonstrating undetectable or low rates of cholesterol esterification and positive filipin staining for free cholesterol in cultured fibroblasts.
The median age at presentation was 1.5 months (range 0.5-10). Bone marrow aspirates showed storage cells in only 7/11 cases. Bone marrow aspirates which had storage cells were undertaken at a median age of 11 months while those with no storage cells were undertaken at median age 2.3 months. The overall sensitivity of bone marrow aspirates for detecting storage cells in children presenting with infantile liver disease was 64%; however, for children who had bone marrow aspirates in the first year of life it was only 57%.
The sensitivity of bone marrow aspirate for the diagnosis of NPC disease in patients presenting with infantile liver disease was lower than previously reported. Where NPC is suspected clinically, definitive investigations should be undertaken promptly. There is a need to develop sensitive screening methods for NPC in children presenting with infantile liver disease.
Article: Lysosomale Transportdefekte[Show abstract] [Hide abstract]
ABSTRACT: Angeborene lysosomale Speichererkrankungen sind gekennzeichnet durch intralysosomale Speicherung von Substanzen, die normalerweise in diesen Organellen ab- oder umgebaut werden. Auf molekularer Ebene beruhen diese Strungen meist auf einer in der Regel angeborenen Defizienz intralysosomaler Hydrolasen bzw. von deren Aktivatoren. Daneben gibt es jedoch auch Strungen im Transport intralysosomaler Substanzen aus den Lysosomen heraus, sog. Transportdefekte. Auch diese fhren zu einer intralysosomalen Einspeicherung von Substanzen. Im Folgenden gehen wir auf die klinisch bedeutsamsten Transporterstrungen ein, nmlich die Zystinose, M.Niemann-Pick TypC und die Sialinsurespeichererkrankung.Lysosomal storage disorders are characterized by intralysosomal storage of compounds which are normally degraded or otherwise metabolized in these organelles. At the molecular level these disorders mainly reflect deficiency of intralysosomal hydrolases or of their activators. Furthermore, dysfunction of transporters which are responsible for the dislocation of compounds out of the intralysosomal space can be found. It is this group of diseases which this review focuses on. These defects lead to intralysosomal storage of compounds as well. In this review we describe the most common lysosomal transport defects which are cystinosis, Niemann-Pick type C disease, and sialic acid storage disease.Monatsschrift Kinderheilkunde 09/2006; 154(10):971-977. DOI:10.1007/s00112-006-1407-3 · 0.28 Impact Factor
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ABSTRACT: Bone marrow aspiration is the preliminary investigation in Niemann Pick disease type A when enzyme assays and mutation studies are unavailable. We report an infant with typical phenotype and enzyme deficiency, but undetectable Niemann Pick cells in the bone marrow. A new mutation R542X in SMPD gene was also detected.Indian pediatrics 06/2012; 49(6):490-2. DOI:10.1007/s13312-012-0095-4 · 1.01 Impact Factor