SPLEEN ENLARGEMENT AS ONLY MANIFESTATION OF NIEMANN PICK DISEASE TYPE C
(Abstract release date: 05/19/16)
EHA Library. López De L. 06/09/16; 134956; PB2056
Ms. Laura López De
Contributions
Contributions
Abstract
Abstract: PB2056
Type: Publication Only
Background
Niemann-Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder (LSD) characterized by multiple lipid storage triggering intracellular impairment trafficking. NPC shows a wide phenotypic spectrum (visceral, neurological and psychiatric manifestations), the most of patients develop symptoms in early childhood; however there are a subtype mainly identified in adults and characterized by aisle spleen enlargement and cytopenias raising the differential diagnosis with a hematologic malignancy.
Aims
The main objective of this study is report probands state NPC only-visceral phenotype and its characterization. Secondary aims are identifying if plasma lysosomal biomarkers can facilitate the differential diagnosis between LSD and haematological malignancies and if that only-visceral phenotype presented genetic differences with neurological phenotypes
Methods
Firstly, plasma lysosomal biomarkers as Chitotriosidase activity (ChT), CCL18/PARC and 7-Ketocholesterol (7-KC) concentrations were assessed trough biochemistry approaches ChT activity was evaluated through an artificial substract, CCL18/PARC concentration using ELISA technique and 7-KC employing liquid chromatography and tandem mass spectrometry. Lastly, genetic characterization of NPC1 and NPC2 genes were carried out. Clinical/analytical records were gathered from the information provided by physicians.
Results
In the last five years, 363 probands were recruited. 51 of them were identified at least one genetic variation reported as pathogenic or unknown significance (VUS) in NPC, 10/51 showed only-visceral symptoms related to NPC.Focused in only visceral cases, they were 35.0 (13.4-41.5) [median (Interquartil range)] years old and a ratio male/female 6/4. None developed neurological symptoms during following-up. Splenomegaly was 16.5 (9.2-18) cm under costal rib in all cases with size information and 1 case presented neonatal jaundice. Hemoglobin 14.5 (12.7-15.3) g/dL, platelets 121.5 (106-231.5) x109/L. Increased biomarkers: ChT activity 119.0 (69.0-266.0) nmol/mL/h, CCL18/PARC and 7-KC concentration were 156.0 (151.0-158.0) ng/mL and 190.3 (103.7-355.9) ng/mL respectively. Four patients had been splenectomized. The histological study showed numerous histiocytic cells, loaded with small vacuoles and lipid appearance (“foamy cells”). These cells were CD68+ and some of them were stained with hard Giemsa blue and PAS positive, diastase resistant, while others showed a slight positivity. Molecular variants identified in NPC1, reported as pathogenic or VUS, were: p.C177T, p.N222S, p.V664M, p.Q775P, p.N916S, p.P1007A, p.D1097N, p.A1151T, p.L1241*, p.R1274T and c.1998+8C>G. NPC2 gene does not show any variations. All genetic variations were found in heterozygosity, 6/10 subjects presented two variants.
Conclusion
The biomarkers CCL18/PARC or 7-KC are increased in all cases that can be analyzed and they constitute good indicators of lysosomal storage disease that might facilitate the differential diagnosis with hematologic malignancies. None of the genetic variants found in NPC1 were exclusively for this only-visceral phenotype.
Session topic: E-poster
Keyword(s): Spleen
Type: Publication Only
Background
Niemann-Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder (LSD) characterized by multiple lipid storage triggering intracellular impairment trafficking. NPC shows a wide phenotypic spectrum (visceral, neurological and psychiatric manifestations), the most of patients develop symptoms in early childhood; however there are a subtype mainly identified in adults and characterized by aisle spleen enlargement and cytopenias raising the differential diagnosis with a hematologic malignancy.
Aims
The main objective of this study is report probands state NPC only-visceral phenotype and its characterization. Secondary aims are identifying if plasma lysosomal biomarkers can facilitate the differential diagnosis between LSD and haematological malignancies and if that only-visceral phenotype presented genetic differences with neurological phenotypes
Methods
Firstly, plasma lysosomal biomarkers as Chitotriosidase activity (ChT), CCL18/PARC and 7-Ketocholesterol (7-KC) concentrations were assessed trough biochemistry approaches ChT activity was evaluated through an artificial substract, CCL18/PARC concentration using ELISA technique and 7-KC employing liquid chromatography and tandem mass spectrometry. Lastly, genetic characterization of NPC1 and NPC2 genes were carried out. Clinical/analytical records were gathered from the information provided by physicians.
Results
In the last five years, 363 probands were recruited. 51 of them were identified at least one genetic variation reported as pathogenic or unknown significance (VUS) in NPC, 10/51 showed only-visceral symptoms related to NPC.Focused in only visceral cases, they were 35.0 (13.4-41.5) [median (Interquartil range)] years old and a ratio male/female 6/4. None developed neurological symptoms during following-up. Splenomegaly was 16.5 (9.2-18) cm under costal rib in all cases with size information and 1 case presented neonatal jaundice. Hemoglobin 14.5 (12.7-15.3) g/dL, platelets 121.5 (106-231.5) x109/L. Increased biomarkers: ChT activity 119.0 (69.0-266.0) nmol/mL/h, CCL18/PARC and 7-KC concentration were 156.0 (151.0-158.0) ng/mL and 190.3 (103.7-355.9) ng/mL respectively. Four patients had been splenectomized. The histological study showed numerous histiocytic cells, loaded with small vacuoles and lipid appearance (“foamy cells”). These cells were CD68+ and some of them were stained with hard Giemsa blue and PAS positive, diastase resistant, while others showed a slight positivity. Molecular variants identified in NPC1, reported as pathogenic or VUS, were: p.C177T, p.N222S, p.V664M, p.Q775P, p.N916S, p.P1007A, p.D1097N, p.A1151T, p.L1241*, p.R1274T and c.1998+8C>G. NPC2 gene does not show any variations. All genetic variations were found in heterozygosity, 6/10 subjects presented two variants.
Conclusion
The biomarkers CCL18/PARC or 7-KC are increased in all cases that can be analyzed and they constitute good indicators of lysosomal storage disease that might facilitate the differential diagnosis with hematologic malignancies. None of the genetic variants found in NPC1 were exclusively for this only-visceral phenotype.
Session topic: E-poster
Keyword(s): Spleen
Abstract: PB2056
Type: Publication Only
Background
Niemann-Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder (LSD) characterized by multiple lipid storage triggering intracellular impairment trafficking. NPC shows a wide phenotypic spectrum (visceral, neurological and psychiatric manifestations), the most of patients develop symptoms in early childhood; however there are a subtype mainly identified in adults and characterized by aisle spleen enlargement and cytopenias raising the differential diagnosis with a hematologic malignancy.
Aims
The main objective of this study is report probands state NPC only-visceral phenotype and its characterization. Secondary aims are identifying if plasma lysosomal biomarkers can facilitate the differential diagnosis between LSD and haematological malignancies and if that only-visceral phenotype presented genetic differences with neurological phenotypes
Methods
Firstly, plasma lysosomal biomarkers as Chitotriosidase activity (ChT), CCL18/PARC and 7-Ketocholesterol (7-KC) concentrations were assessed trough biochemistry approaches ChT activity was evaluated through an artificial substract, CCL18/PARC concentration using ELISA technique and 7-KC employing liquid chromatography and tandem mass spectrometry. Lastly, genetic characterization of NPC1 and NPC2 genes were carried out. Clinical/analytical records were gathered from the information provided by physicians.
Results
In the last five years, 363 probands were recruited. 51 of them were identified at least one genetic variation reported as pathogenic or unknown significance (VUS) in NPC, 10/51 showed only-visceral symptoms related to NPC.Focused in only visceral cases, they were 35.0 (13.4-41.5) [median (Interquartil range)] years old and a ratio male/female 6/4. None developed neurological symptoms during following-up. Splenomegaly was 16.5 (9.2-18) cm under costal rib in all cases with size information and 1 case presented neonatal jaundice. Hemoglobin 14.5 (12.7-15.3) g/dL, platelets 121.5 (106-231.5) x109/L. Increased biomarkers: ChT activity 119.0 (69.0-266.0) nmol/mL/h, CCL18/PARC and 7-KC concentration were 156.0 (151.0-158.0) ng/mL and 190.3 (103.7-355.9) ng/mL respectively. Four patients had been splenectomized. The histological study showed numerous histiocytic cells, loaded with small vacuoles and lipid appearance (“foamy cells”). These cells were CD68+ and some of them were stained with hard Giemsa blue and PAS positive, diastase resistant, while others showed a slight positivity. Molecular variants identified in NPC1, reported as pathogenic or VUS, were: p.C177T, p.N222S, p.V664M, p.Q775P, p.N916S, p.P1007A, p.D1097N, p.A1151T, p.L1241*, p.R1274T and c.1998+8C>G. NPC2 gene does not show any variations. All genetic variations were found in heterozygosity, 6/10 subjects presented two variants.
Conclusion
The biomarkers CCL18/PARC or 7-KC are increased in all cases that can be analyzed and they constitute good indicators of lysosomal storage disease that might facilitate the differential diagnosis with hematologic malignancies. None of the genetic variants found in NPC1 were exclusively for this only-visceral phenotype.
Session topic: E-poster
Keyword(s): Spleen
Type: Publication Only
Background
Niemann-Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder (LSD) characterized by multiple lipid storage triggering intracellular impairment trafficking. NPC shows a wide phenotypic spectrum (visceral, neurological and psychiatric manifestations), the most of patients develop symptoms in early childhood; however there are a subtype mainly identified in adults and characterized by aisle spleen enlargement and cytopenias raising the differential diagnosis with a hematologic malignancy.
Aims
The main objective of this study is report probands state NPC only-visceral phenotype and its characterization. Secondary aims are identifying if plasma lysosomal biomarkers can facilitate the differential diagnosis between LSD and haematological malignancies and if that only-visceral phenotype presented genetic differences with neurological phenotypes
Methods
Firstly, plasma lysosomal biomarkers as Chitotriosidase activity (ChT), CCL18/PARC and 7-Ketocholesterol (7-KC) concentrations were assessed trough biochemistry approaches ChT activity was evaluated through an artificial substract, CCL18/PARC concentration using ELISA technique and 7-KC employing liquid chromatography and tandem mass spectrometry. Lastly, genetic characterization of NPC1 and NPC2 genes were carried out. Clinical/analytical records were gathered from the information provided by physicians.
Results
In the last five years, 363 probands were recruited. 51 of them were identified at least one genetic variation reported as pathogenic or unknown significance (VUS) in NPC, 10/51 showed only-visceral symptoms related to NPC.Focused in only visceral cases, they were 35.0 (13.4-41.5) [median (Interquartil range)] years old and a ratio male/female 6/4. None developed neurological symptoms during following-up. Splenomegaly was 16.5 (9.2-18) cm under costal rib in all cases with size information and 1 case presented neonatal jaundice. Hemoglobin 14.5 (12.7-15.3) g/dL, platelets 121.5 (106-231.5) x109/L. Increased biomarkers: ChT activity 119.0 (69.0-266.0) nmol/mL/h, CCL18/PARC and 7-KC concentration were 156.0 (151.0-158.0) ng/mL and 190.3 (103.7-355.9) ng/mL respectively. Four patients had been splenectomized. The histological study showed numerous histiocytic cells, loaded with small vacuoles and lipid appearance (“foamy cells”). These cells were CD68+ and some of them were stained with hard Giemsa blue and PAS positive, diastase resistant, while others showed a slight positivity. Molecular variants identified in NPC1, reported as pathogenic or VUS, were: p.C177T, p.N222S, p.V664M, p.Q775P, p.N916S, p.P1007A, p.D1097N, p.A1151T, p.L1241*, p.R1274T and c.1998+8C>G. NPC2 gene does not show any variations. All genetic variations were found in heterozygosity, 6/10 subjects presented two variants.
Conclusion
The biomarkers CCL18/PARC or 7-KC are increased in all cases that can be analyzed and they constitute good indicators of lysosomal storage disease that might facilitate the differential diagnosis with hematologic malignancies. None of the genetic variants found in NPC1 were exclusively for this only-visceral phenotype.
Session topic: E-poster
Keyword(s): Spleen
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