1 DIAGNOSTIC AND PROGNOSTIC UTILITY OF PLASMA CHITOTRIOSIDASE IN COMPARISON TO PLASMA TOTAL ACID PHOSPHATASE ACTIVITY, FERRITIN AND GLOBULIN IN… [602292]

1 DIAGNOSTIC AND PROGNOSTIC UTILITY OF
PLASMA CHITOTRIOSIDASE IN COMPARISON TO
PLASMA TOTAL ACID PHOSPHATASE ACTIVITY,
FERRITIN AND GLOBULIN IN GAUCHER'S
DISEASE
Mohammed H. Hassan1*, Ayat A. Sayed2, Tahia H.
Saleem2, Ahmed El -Abd Ahmed3, Khalid I. Elsayh4

Brief running head : Biomarkers in Gaucher's disease
1Department of Medical Biochemistry and Molecular Biology, Qena
Faculty of Medicine, South Valley University, P.O. Box No. 83523
Qena, Egypt.
2Department of Medical Biochemistry and Molecular Biology,
Faculty of medicine, Assiut University, P.O. Box 71515, Assiut,
Egypt.
3Department of Pediatrics, Qena Faculty of Medicine, South Valley
University, P.O. Box No. 83523 Qena, Egypt.
4Department of P ediatrics, Faculty of medicine, Assiut University,
P.O. Box 71515, Assiut, Egypt.
Corresponding author: *To whom correspondence should be
addressed:
Dr. Mohammed H. Hassan , Lecturer of Medical Biochemistry and
Molecular Biology, Qena Faculty of Medicine, South Valley
University, Qena, Egypt.
Email: [anonimizat];
[anonimizat] ;
Tel.: +201098473605.

2 ABSTRACT
Gaucher disease "GD" is one of the most common glycolipid storage
disorders . We investigate the validity of using plasma chitotriosidase
"ChT", total acid phosphatase activity , ferritin , and globulin in predicting
and / or therapeutic monitoring of pediatric patients with GD. A cross
sectional case control study , carried out on 60 pediatric patients (40 GD
patients, subdivided into group on ERT and group not receiving ERT, and 20
patients suspected to have GD), and in addition to 20 healthy age and sex
matched controls. Significantly higher plasma ChT and total acid
phosphatase in GD patients not receiving ERT versus the suspected GD
patients (P-value <0.05 ), both markers have the highest AUC, sensitivity and
specificity. Significant higher plasma levels of ChT, total acid phosphatase
activity , ferritin and globulin among GD not receiving ERT versus both GD
on ERT and Control group .Positive correlation between plasma ferritin and
total ac id phosphatase activity (r = 0.465 and P -value <0.05). In conclusions:
Plasma ChT and total acid phosphatase activity , both together are more
reliable in screening for GD. Plasma ChT, total acid phosphatase activity ;
ferritin and globulin are collectively helpful in evaluation and follow up the
effect of ERT.

Keywords : Chitotriosidase; Total acid phosphatase activity ; F erritin;
Globulin; Gaucher 's disease markers .

3 INTRODUCTION

Gaucher disease "GD" is one of the most common glycolipid
storage disorders , caused by a genetic deficiency of lysosomal β –
glucocerebrosidase, encoded by GBA gene, leading to accumulation
of the substrate glucocerebroside in the cells of the macrophage –
monocyte system (Thomas et al., 2014) . Glucocerebroside engorged
cells, termed Gaucher cells, infiltrate various organs (Boven et al.,
2004) , leading to multisystem organomegaly, pancytopenia and bone
complication (Grabowski et al., 2014). Molecular genetic analysis is
the standard for confirmation of the diagnosis of GD, and offers
certain advantages over glucocerebrisdase activity assays, including
superior DNA stability, and accurate carrier status determination, and
potential to establish certain genotype/phenotype correlations
(Brautbar et al., 2008) . GD is one of the few lysosomal storage
diseases "LSDs" for which treatment has been developed. ERT is one
of the most used today, but substrate synthesis inhibition is also
available (Jmoudiak and Futerman , 2005) .
Several circulating molecules thought to be secreted by
Gaucher cells have been studied as biological markers of disease
burden and/ or response to enzyme replacement therapy "ERT" (Aerts

4 et al., 2005) . Among these molecules, chitotriosidase, acid
phosphatase and ferritin (Thomas et al., 2014; van Dussen et al.,
2014) . Chitotriosidase enzyme (ChT; EC 3.2.1.14) is a human
chitinase member of family 18 -glycosyl -hydrolases that catalyzes the
hydrolysis of natural chitin, which is remarkably homologous to
chitinases from plants, bacteria, fungi, nematodes and insects
(Nagpure et al., 2014) , secreted by active tissue macrophages
(Sheth et al., 2010) . The clinical utility of plasma ferritin and total
acid phosphatase activity as biomarker s of disease severity and
prognosis in GD is still debated (Koppe et al., 2016; Robinson and
Glew , 1980) . The infiltrated reticuloendothelial organ such as
Gaucher spleen, may contribute to the production of monoclonal
immunoglobulin (Pratf et al., 1968) with overall increase in the
plasma globulin levels.
Research on various biochemical markers of Gaucher disease
will provide insight into the pathophysiology of the disease and allow
the clinician s to pick up GD cases early, predict clinical severity and
assess the response in patients receiving ERT. A collection of plasma
biomarkers in the form of plasma ChT , total acid phosphatase activity ,
ferritin and globulin were studied to test which is the best predictor and can
be used as primary screening marker for GD before making mutation

5 analysis . Also , to confirm that if their plasma levels will be affected by
ERT in GD patients .
MATERIAL S AND METHODS
The present study is a cross sectional case control study, was carried
out 60 pediatric patients divided into three groups; Group A ( GD
patients) divided into Group A1: it includes 20 pediatric patients with
proved diagnosis of Gaucher disease and receiving the ERT 4 years or
more with imiglucerase (Cerezyme, 60 U/kg/2weeks by intravenous
infusion over 1 –2 hrs) and Group A2: it includes 20 pediatric patients
with proved diagnosis of Gaucher disease and not receiving the ERT ;
Group B: it includes 20 pediatric patients have the inclusion criteria of
Gaucher disease , in addition to 30 apparently healthy children, age and sex
matched selected as control group. They were recru ited from the pediatric
outpatient clinics and inpatients Pediatric departments of Assiut and Qena
University hospitals, which are of the major tertiary referral pediatric
hospitals in Upper Egypt after approval of the university hospital ethical
committee . Prior to initiation of the study; every subject and his/her
parents were informed about the aim of the study and gave a written
consent. The study was carried out during the period from January 2015
to May 2016. The comparison between group A2 and group B to evaluate
the screening power of the included biomarkers, while, the comparison

6 between groups A1, A2 and group C to evaluate the therapeutic
monitori ng efficacy of such biomarkers.
Inclusion criteria (Irún et al., 2013) ; clinically : unexplained
isolated splenomegaly or hepatosplenomegaly with skeletal
abnormalities (bone pain or spontaneous fractures) associated with or
without delayed physical and /or mental development and/ or
neurologic abnormalities. Laboratory: anemia and/or
thrombocytopenia to be confirmed by the mutation analysis.
Complete blood counts "CBC", albumin, globulin, alkaline
phosphatase "ALP", bilirubin (total and direct), liver enzymes (ALT
and AST) were taken already from the file of the patients. Complete
blood counts "CBC" were measured using (Cell Dyn 1800 -Abbott
diagnostics, Germany). Liver function tests including albumin,
globulin, A/G ratio, alkaline phosphatase "ALP", bilirubin (total &
direct) and liver enzymes (ALT & AST) were estimated using [Cobas
C311 (Roche diagnostics, Germany)].
Five cc of venous blood was drawn from the included children and
divided into two tubes: 3 cc on EDTA tubes, centrifuged at 3500 rpm
for 15 min and the separated plasma from each tube was stored into
aliquots using 1 ml cryotubes at – 20° C until biochemical analysis (for

7 ferritin, total acid phosphatase activity and ChT assays in all studied
groups and plasma protein electrophoresis in group A only). 2 cc on
another EDTA tubes, stored at – 20° C till the time of mutation a nalysis
using strip assay method .
Using commercially available enzyme -linked immune -sorbent
assay (ELISA) assay kit s (using ELISA multiskan EX microplate
photomter, thermo scientific, STAT FAX -2100, USA ) according to
manufacturer protocol for measurements of plasma ChT (supplied by
Elabscience Biotechnology Co.,Beijing, Catalog No: E -EL-H5620)
and plasma Ferritin ( supplied by BIOCHECK, INC, 323 Vintage Park
Dr., Foster City, CA 94404 – Catalog Number: BC -1025).
Using commercially available colorimetric assay kit (using T60
UV visible spectrophotometer. PG INSTRUMENTS LIMITED, Alma
park wibtoft, Leicester shreshire, England. LE17SBE. Serial No. 20 –
1650 -01-0010 ) according to manufacturer protocol for measurement
of plasma total acid phosphatase activity (suppli ed by Bio -Diagnostic
Co. Cairo, Egypt, Catalog No: AC 10 10).
Using commercially available strip assay kit for mutation analysis
supplied by Vienna Lab Diagnostics GmbH, Gaudenzdorfer Guertel
43-45, A -1120 Vienna, Austria: The procedure included three steps:

8 (1) DNA isolation, (2) polymerase chain reaction "PCR" amplification
using biotinylated primers (using VeriFlex™ 96 -Well Thermal
Cycler, Applied Biosystems , USA), (3) hybridization of amplification
products to a test strip containing allele -specific oligonucleotide
probes immobilized as an array of parallel lines. Bound biotinylated
sequences were detected using streptavidin -alkaline phosphatase and
color su bstrates.
Plasma protein electrophoresis (Fig.1) was performed using Sebia
capillary electrophoresis , Sebia, Inc. according to manufacturer's
guidelines. Plasma proteins were separated into 6 components;
albumin, alpha1, 2, beta1, 2 and gamma globulin. The separation was
carried out on silica capillaries according to their electrophoresis
mobility and elctroosmotic flow at high voltage in alkaline media.
Analys is of data was done by IBM computer using SPSS
(statistical program for social science version 12) as follows :
Description of quantitative variables as mean ±SD .Description of
qualitative variables as number and percentage. Unpaired t -test was
used to com pare quantitative variables, in parametric data. Correlation
co-efficient test was used to rank variables positively or inversely. P

9 value >0.05 insignificant, P<0.05 significant, P<0.001 highly
significant.
RESULTS
Regarding the demographic and clinical data of the studied groups; group A
(mean age 6.20 years ±5.88 SD) (11 males, 9 females); group B (mean age
6.04 years ±4.99SD) (9 males, 11 females) ; group C (mean age 8.07 ±5.50
SD) (17 males, 13 females) , 32 (80%) have non -neuropathic type 1 GD and
8 (20%) have type 3 GD. Regarding the frequency distribution of group B
cases according to the final diagnoses; mutation analysis for GD was
positive in three cases out of 20 (15%), unclassified metabolic disor ders
were present in 6 cases (30%), leukemia was the diagnosis in 6 cases (30 %),
glycogen storage disease type –I in two cases (10%), three cases died before
completing the investigatory battery (15%).
Regarding the genotypes detected in the studied GD patients;
homozygous for the mutation L444P ( 30.8%), homozygous for the mutation
N370S (15.4%), heterozygous for the
mutations N370S and rec Ncil (15.4%), heterozygous for IVS2 +1 and rec
NciI (11.5%), heterozygous for IVS2 +1 and L444P (7.7%), heterozygous
for L444P and second alleles were not detected was occurred in 7.7%, while,
in 11.5% it was not possible to identify any of the allele.
Comparison between group A2 and B as regard hemoglobin levels,
platelets count, plasma chitotriosidase, total acid phosphatase, ferritin,

10 globulin and A/G ratio (Table 1 ), showing significantly higher plasma
chitotriosidase and total acid phosphatase in group A2 versus B (P-value
was <0.05 ).Regarding the d iagnostic utility of ChT , total acid phosphatase,
ferritin, globulin and A/G ratio in diagnosing GD (group A2 and group B) ,
plasma chitotriosidase showed the highest area under the curve (AUC=
0.897) followed by total acid phosphatase (AUC= 0.879) , then ferritin
(AUC= 0.762) followed by A/G ratio (AUC= 0. 689) and Globulin
showed the lowest AUC (= 0.631) ( Table 2 and Fig. 2).
Significant higher plasma levels of chitotriosidase, ferritin and
lower platelet count among group A2 when compared with group A1
and group C (P-value was <0.05and < 0.001respectively for each).
Significant higher plasma levels of total acid phosphatase activity and
lower hemoglobin levels among group A2 when compared with group
A1 and group C (P-value was <0.001 a nd <0.001respectively for each)
(Table 3 and Table 4). There was p ositive correlation between plasma
ferritin level and plasma total acid phosphatase activity (r = 0.465 and
P-value was <0.05) (Fig.3 ).
DISCUSSION
ChT is dramatically induced in disease states where tissue -resident
macrophages are chronically activated. It is released by Gaucher storage
cells and is increased in the plasma of Gaucher patients (Irún et al., 2013) .

11 However, the limitation of ChT as a mark er of GD is that, 3 -5 % of
individuals in the general population have no activity due to the
presence of a null allele in the ChT gene (Sheth et al., 2010) . The
increased serum acid phosphatase activity in patients with GD arises
by spillage of the enzyme from the glucocerebroside -rich storage cells
of the spleen and other tissues (Crocker et al., 1960) .
The findings of the present study revealed that plasma ChT has the
highest area under curve, high plasma ChT and ferritin have the highest
sensitivity, while, high total acid phosphatase activity, and globulin and low
A/G ratio have the highest specificity in diagnosing GD. All these
biomarkers are better negative than positive in predicting GD. Comparison
betwe en the plasma levels of such biomarkers among group A2 versus group
B showed significant higher plasma ChT and total acid phosphatase
activity in group A2 than in group B, indicating that plasma ChT and
total acid phosphatase activity are the best screenin g markers could be
used for predicting GD patients.
Regarding the effect of ERT on some laboratory parameters
related to pediatric patients with GD , the present study showed
significant higher plasma levels of ChT, ferritin and lower platelet
count amon g among group A2 when compared with group A1 and
group C, (P -value was <0.05and <0.001respectively for each ),

12 significant higher total acid phosphatase activity and lower
hemoglobin levels among group A2 when compared with group A 1
and group C (P-value wa s <0.001 and <0.001respectively for each),
while , total leukocytic count (TLC) showed non -significant
differences among group A2 when compared with group A 1 and
group C.
Although the comparison regarding the previous laboratory
parameters wasn't in the same group of patients pre and post -ERT
because the study is a cross sectional and some of the laboratory data
of group A1 before the therapy were deficient but still signif icant
differences between group A1 and A2 were present. In agreement
with these findings, a study done by Souza et al. (2014) found that
GD patients had significantly lower levels of hemoglobin and platelet
count at diagnosis when compared with two years following the ERT
with non -significant changes for TLC after treatment. Also, a study
done by Sumarac et al. (2011) on patients with GD , reported higher
plasma levels of ChT, total acid phosphatase and ferritin before ERT
with significant initial decrease in their plasma levels following ERT.
Another study done by Stein et al. (2010) on patients with a diagnosis
of GD, demonstrated an impressive elevation of plasma ferritin in GD
with significant decrease in ferritin level after the ERT.

13 With regard to physiological function, it is noteworthy that
during the digestion of erythrocytes by spleen macrophages the
disappearance of hemoglobin is followed by an increase in the numbe r
of ferritin granules and in acid phosphatase activity in lysosomes
(Spor, 1970) . In the present study, there was a positive correlation
between plasma ferritin level and total acid phosphatase activity with
non- significant correlation neither between plasma ferritin level s and
plasma ChT levels nor between total acid phosphatase activity and
plasma ChT levels . On the contrary, a study done by Cabrera –
Salazar et al. (2004) found significant positive correlation between
plasma total acid phosphatase acti vity and plasma ChT activity among
GD patients. Also another study done by Sumarac et al. (2011)
reported a significant positive correlation between plasma total acid
phosphatase activity and plasma ChT activity and non -significant
correlations between fer ritin and any of the other two biomarkers
among GD patients.
The mechanism explaining the relationship between GD and
immunoglobulin abnormalities is far from understood (de Fost et al.,
2008) . The findings of the present study revealed a significant higher
plasma levels of globulin among group A 1 and group A2 when
compared with group C (P -value <0.001 for both), with statistically

14 significant lower albumin/ globulin ratio (A/G ratio) in group A 1 and
group A2 in comparison with group C (P -value <0.001 for both) .
Plasma protein electrophoresis revealed polyclonal
hypergammaglobulinemia in 60% of group A1 and in 50 % of group
A2. In agreement with these findings a study done by
Arıkan‐Ayyıldız et al. (2011) on pediatric patients with GD found
that hyper immunoglobulinemia was present in 77%, 66%, and 60% at
diagnosis, before initiation of ERT, and after ERT, respectively.
In conclusions; The present study prove that p lasma ChT
combined with total acid phosphatase activity are the most helpful
prima ry screening biomarkers for GD , while, plasma ChT , total acid
phosphatase activity , ferritin and globulin are together helpful
prognostic biomarkers in monitoring patient response, with GD, to
the effect of ERT .

ACKNOWLEDGMENT S: We would like to acknowledge the team
work of the Metabolic and Genetic Disorders Unit – Faculty of
Medicine – Assiut University , where the laboratory work of this study
has been done . Special thanks to Prof. Abbas Mansour, the president
of South Valley University and Prof. Hamdy M. Hussien, the Dean of
Qena faculty of Medicine.

15 References
1. Aerts JM, Hollak CE, van Breemen M, Maas M, Groener JE
and Boot RG (2005) : Identification and use of biomarkers in
Gaucher disease and other lysosomal storage diseases. Acta
Paediatr Suppl . 94:43 -46.
2. Arıkan -Ayyıldız Z, Yuce A, Uslu -Kızılkan N, Demir H and
Gurakan F (2011) :Immunoglobulin abnormalities and effects of
enzyme replacement therapy in children with Gaucher disease.
Pediatr Blood Cancer .56: 664–666.
3. Boven LA, van Meurs M and Boot RG (2004) : Gaucher cells
demonstrate a distinct macrophage phenotype and resemble
alternatively activated macrophages. Am J Clin Pathol .122:359 -69.
4. Brautbar A , Abrahamov A , Hadas -Halpern I , Elstei n D and
Zimran A (2008) : Gaucher disease in Arab patients at an Israeli
referral clinic. Isr Med Assoc J . 10:600 -602.
5. Cabrera -Salazar MA , O'Rourke E , Henderson N , Wessel H
and Barranger JA (2004) : Correlation of surrogate markers of
Gaucher disease: implications for long -term follow up of enzyme
replacement thera py. Clin Chim Acta . 344:101 -107.
6. Crocker AC and Landing BH (1960) : Phosphatase studies in
Gaucher’s disease. Metabolism .9:341 -362.
7. de Fost M, Out TA, de Wilde FA, Tjin E, Pals S, van Oers M,
Boot R, Aerts J, Maas M, vom Dahl S and Hollak C (2008) :
Immunoglobulin and free light chain abnormalities in Gaucher
disease type I: data from an adult cohort of 63 patients and review
of the literature . Ann Hematol . 87:439 –449
8. Irún P, Alfonso P, Aznarez S, Giraldo P and Pocov M (2013) :
Chitotriosidase variants in patients with Gaucher disease.
Implications for diagnosis and therapeutic monitoring. Clin
biochem . 46:1804 -1807.
9. Jmoudiak M and Futerman AH (2005 ): Gaucher disease:
pathological mechanisms and modern management. Br J
Haematol . 129:178 -188.
10. Koppe T , Doneda D , Siebert M , Paskulin L , Camargo
M, Tirelli KM , Vairo F , Daudt L and Schwartz IV (2016) : The
prognostic value of the serum ferritin in a southern Brazilian
cohort of patients with Gaucher disease. Genet Mol Biol . 39:30-
34.

16 11. Nagpure A, Choudhary B and Gupta RK (2014) : Chitinases: in
agriculture and human healthcare. Crit Rev Biotechnol .34:215 –
232.
12. Pratf P, Estren S and Kochwa S (1968) : Immunoglobulin
abnormalities in Gaucher’s disease report of 16 Cases . Blood . 31:
633-640.
13. Robinson D and Glew1 R (1980) : Acid phosphatase in Gaucher’s
disease. Clin. Chem . 26: 37 1-382.
14. Sheth JJ, Sheth FJ, Oza NJ, Gambhir PS, Dave UP and Shah
RC (2010) : Plasma Chitotriosidase Activity in Children with
Lysosomal Storage Disorders. Indian J Pediatr . 77: 203 -205.
15. Souza AMA, Muniz TP and Brito RM (2014) : Study of enzyme
replacement therapy for Gaucher Disease: comparative analysis of
clinical and laboratory parameters at diagnosis and after two, five
and ten years of treatment. Rev Bras Hematol Hemoter . 36:345–
350.
16. Spor S (1970) : Electron microscopic study on acid phosphatase of
macrophages during the breakdown of erythrocytes in the spleen
of the rat. Blut .21: 244-250.
17. Stein P, Yu H, Jain D and Mistry PK (2010) : Hyperferritinemia
and Iron Overload in Type 1 Gaucher Disease. Am J Hematol . 85:
472-476.
18. Sumarac Z , Suvajdžić N , Ignjatović S , Majkić -Singh
N , Janić D , Petakov M , Dorđević M , Mitrović M , Dajak
M , Golubović M and Rodić P (2011) : Biomarkers in Serbian
patients with Gaucher disease. Clin biochem . 44: 950 –954.
19. Thomas AS, Mehta A and Hughes DA (2014) : Gaucher disease:
haematological presentations and complications . Br J Haematol .
165:427 –440.
20. van Dussen L, Hendriks EJ, Groener JE, Boot RG , Hollak CE
and Aerts JM (2014) : Value of plasma chitotriosidase to assess
non-neuronopathic Gaucher disease severity and progression in
the era of enzyme replacement therapy. J Inherit Metab Dis . 37:
991-1001.
Internet Resources : Grabowski GA, Petsko GA, Kolodny EH (2014).
Gaucher Disease. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW,
Antonarakis SE, Ballabio A, Gibson K and Mitchell G (eds), OMMBID –
The Online Metabolic and Molecular Bases of Inherited Diseases,
http://ommbid.mhmedical.com/content . aspx?bookid = 474&Sectionid =
45374148 (accessed August 20, 2014)

17
Table 1- Comparison between the mean plasma biomarkers
(hemoglobin levels, platelets count, plasma, ferritin, chitotriosidase,
total acid phosphatase, A/G ratio and globulin) between group A 2 and
B .
Variables Group A2
(n= 20) Group B
(n= 20) P-value
Hb level (g/dl) 9.46±2.41 9.41±1.93 0.849
Platelet count (x103
mm-3) 148.31±102.56 154.38±123.44 0.870
Plasma ferritin
(ng/ml) 476.69±336.84 703.83±307.65 0.127
Plasma
chitotriosidase
(pg/ml) 2134.27±965.43 1186.08±439.58 0.01*
Plasma total acid
phosphatase activity
(U/L) 26.99±12.58 17.73±5.37 0.01*
A/G ratio 1.32 ± 0.29 1.48 ± 0.36 0.384
Golbulin (g/dl) 2.90 ± 0.84 2.73 ± 0.69 0.549
Positive mutation
analysis
No. (%) 20 (100) 3 (15) –

P value >0.05 insignificant, * P<0.05 significant, **P<0.001 highly
significant

18

Table 2-Performance characteristics of chitotriosidase, total acid
phosphatase, ferritin, globulin and A/G ratio in diagnosing GD
Variables Chitotriosidase
(pg/ml) Total acid
phosphatase
(U/L) Ferritin
(ng/ml) Globulin
(g/dl) A/G
ratio
Best cut
off > 943 > 20 > 141 > 3 ≤
1.18
AUC 0.897 0.879 0.762 0.631 0.689
Sensitivity 92.31 76.92 84.62 53.85 46.15
Specificity 73.81 90.48 66.67 90.48 95.24
PPV 52.2 71.4 44.0 63.6 75.0
NPV 96.9 92.7 93.3 86.4 85.1
Accuracy 78.18 87.3 70.9 81.8 83.6

19 Table 3- Comparison between the studied groups (group A1,
group A2 and group C) regarding complete blood count and liver
function tests

Variables Group A1
(n =20) Group A2
(n= 20) Group C
(n= 30)
P-value
P1 P2 P3
Complete blood count parameters:
Hemoglobin (g/dl, mean ± SD ) 12.30±1.30 9.13±2.22 12.92±0.85 .000** .070 .000**
White blood cell count (x
10⁹/L,mean ± SD ) 7.32±2.37 5.80±2.61 6.94±1.63 .134 .554 .088
Platelet count (x 10 ⁹/L, mean
± SD ) 220.85±104.25 109.00±58.35 264.20±61.40 .003* .095 .000**
Liver function tests:
Total bilirubin (mg/dl, mean ±
SD) 8.62±4.30 12.33±4.70 10.15±2.98 .051 .185 .079
Direct bilirubin (mg/dl, mean
± SD ) 1.96±1.13 2.43±0.89 2.80±0.93 .072 .061 .699
Aspartate transaminase (AST)
(U\l, mean ± SD ) 35.85±14.62 47.41±33.12 30.93±5.52 .264 .114 .011*
Alanine transaminase (ALT)
(U\l, mean ± SD ) 18.615±9.55 20.58±10.06 21.17±6.68 .322 .128 .068
Alkaline phosphatase (ALP)
(U\l, mean ± SD ) 188.15±47.97 160.67±78.11 194.90±59.87 .296 .312 .082
Albumin (g/dl, mean ± SD ) 3.64±0.73 3.68±0.57 3.88±0.30 .866 .122 .141
Globulin (g/dl, mean ± SD ).
Polyclonal
hypergammaglobulinemia
(NO., %). 4.23±0.88

12 (60%) 3.23±0.63

10 (50%) 2.53±0.33

–- .006*

–- .000**

–- .000**

–-
A/G ratio( mean ± SD ) 0.91±0.27 1.24±0.28 1.55±0.19 .008* .000** .000**
P1: A1 versus A2 – P2: A1 versus C – P3: A2 versus C.
P value >0.05 insignificant, * P<0.05 significant, **P<0.001 highly
significant

20 Table 4- Comparison between the studied groups regarding
plasma chitotriosidase level, ferritin level and t otal acid
phosphatase activity

P1: A1 versus A2 – P2: A1 versus C – P3: A2 versus C.
P value >0.05 insignificant, * P<0.05 significant, **P<0.001 highly
significant .

Variables Group A1
(n =20) Group A2
(n= 20) Group C
(n= 30) P-value
Mean ± SD Mean ± SD Mean ± SD P1 P2 P3
Plasma
chitotriosidase
(pg/ml) 1366.46±444.83 2134.27±965.43 624.55±375.24 0.038* 0.000** 0.000**
Plasma ferritin
(ng/ml) 190.42 ± 144.93 476.69 ± 336.84 69.89 ± 59.93 0.017* 0.001* 0.000**
Plasma total
acid
phosphatase
activity (U/L) 13.53± 1.73 26.99 ± 12.58 11.59 ± 4.17 0.000** 0.067 0.000**

21 Figures legends
Fig.1- Plasma protein electrophoresis; A) Normal. B) Polyclonal
hypergammaglobulinemia with inverted A/G ratio.

Fig.2- Combined ROC curve analysis of plasma chitotriosidase (A);
Total acid phosphatase, ferritin, globulin and A/G ratio (B).
Chitotriosidase .

Fig.3- Correlation between plasma ferritin and total acid phosphatase
activity among GD patients showing positive correlation.

22

A B
A

23

Chitotriosidase.Pg.ml
0 20 40 60 80 100020406080100
100-SpecificitySensitivity
B A

24

25
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الذور التشخٍصً والتىبؤي للكٍتىترٌىرٌذٌز مقاروة بىشاط الفىسفاتٍز
الحامضى الكلً , الفرٌتٍه والجلىبٍىلٍه فً داء جىشٍه
محمذ حسىً حسان1, أٌات عبذالرحمه سٍذ2, تحٍة هاشم سلٍم2 , أحمذالعبذ
أحمذ3, خالذ الساٌح4
قسى انكًٍٍاء انحٍىٌت انطبٍت بكهٍت طب قُا1 وأسٍىغ2- قسى طب األطفال
وحذٌثً انىالدة بكهٍت طب قُا3 وأسٍىغ4
مقذمه: داء خىشٍت هى واحذ يٍ اظطشاباث حخضٌٍ انشحىو انسكشٌت األكثش
شٍىعا.
الهذف مه الذراسة : حقٍٍى اسخخذاو ا نكٍخىحشٌىرٌذٌض يقاسَت بُشاغ انفىسفاحٍض
انحايعى انكهً , انفشٌخٍٍ واندهىبٍىنٍٍ فً انخُبؤ وانًشاقبت انعالخٍت نألطفال
انًصابٍٍ بذاء خىشٍه .
المرضً وطرق البحث : أخشٌج انذساست عهً 06 ( طفم يشٌط 06 طفم
يشٌط بذاء خىشٍه وانزٌٍ حى حقسًٍهى نًدًىعخٍٍ ( 06 طفم ٌخهقً انعالج
االحالنً نالَضٌى انُاقص وانًخسبب فً هزا انًشض و06 طفم ال ٌخهقً انعالج
االحالنً) و06 طفم يشخبت اٌ ٌكىٌ نذٌهى االصابت بذاء خىشٍه يٍ األطفال
انًشظً انًخشددٌٍ عهً انعٍاداث انخاسخٍت أو انًحدىصٌٍ باألقساو انذاخهٍت
بًسخشفً قُا وأسٍىغ اندايعً . هزا باالظافت انً 06 طفم صحٍح يخىافقا
خُسا وعًشا يع يدًىعت انًشظً حى اخخٍاسهى كًدًىعت ظابطت. حى قٍاط
انكٍخىحشٌىرٌذٌض و انفشٌخٍٍ فً بالصيا انًشظً وانًدًىعت انعابطت باسخخذاو
االنٍضا بًٍُا حى قٍاط يسخىي َشاغ انفىسفاحٍض انحايعى انكهً واندهىبٍىنٍٍ
كًٍٍائٍا.
وتائج الذراسة: أظهشث َخائح انذساست أٌ انكٍخىحشٌىرٌذٌض و َشاغ انفىسفاحٍض
انحايعً انكهً يعا هًا األكثش افادة فً انخبؤ بذاء خىشٍه بٍُ ًا
انكٍخىحشٌىرٌذٌض ,َشاغ انفىسفاحٍض انحايعى انكهً , انفشٌخٍٍ واندهىبٍىنٍٍ يعا
اكثش افادة فً انًشاقبت انعالخٍت نهؤالء انًشظً ويخابعه حأثٍش انعالج االحالنً
نالَضٌى انُاقص عهً ححسٍ انحانت انصحٍت نذٌهى وهً دساست راث دالنت
احصائٍت.