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B. van Dooijeweert et al.
Metabolic profiles reflect PKD disease severity
In order to explore the heterogeneity of PKD metabolic profiles in relation to clinical phenotype, PCA and PLS- DA were performed for the entire group of patients and controls. Based on presence of spleen and transfusion fre-
quency phenotypes were distinguished as mild, moder- ate and severe. Most resemblance to controls in metabol- ic profile was clear for mild phenotypes, followed by severely affected patients (Online Supplementary Figure S4).
Table 1A.Clinical characteristics of pyruvate kinase deficiency patients and baseline comparison to healthy controls
Age (yrs)
65
2 6
51 28
29 23
35 48
25
48
21 51
24
20
46
Normal range*
Sex
female
female female
female male
female female
male female
male
male
male female
male
Hb RBC Retics WBC Plts (mmol/L) (x1012/L) (x109/L) (x109/L) (x109/L)
Treatment
splenectomy; no current treatment
regular transfusions
splenectomy; sporadic transfusion
no current treatment
splenectomy; sporadic transfusion
no current treatment
splenectomy; no current treatment
no current treatment
splenectomy; no current treatment
splenectomy; no current treatment
splenectomy; no current treatment
no current treatment
splenectomy; regular transfusions
splenectomy; no current treatment
regular transfusions
no current treatment
150-450
Allele 1
c.1178A>G; p.(Asn393Ser)
c.331G>A; p.(Gly111Arg) c.331G>A; p.(Gly111Arg)
c.1456C>T; p(Arg486Trp) c.1073G>A; p.(Gly358Glu)
c.142_159del; p.(Thr48_Thr53 del)
c.1269G>A; p.(Met373_Ala423del;0)
c.194T>C; p.(Met65Thr) c.1462C>T; p(Arg488*)
c.142_159del; p.(Thr48_Thr53 del)
c.376-2A>C; p. (?)
c.390_392het_delCAT; p.(Ile131del) c.507+1G>A; p.[=;0]
c.694G>T; p.(Gly232Cys)
c.1529G>A; p.(Arg510Gln) c.1121T>C; p.(Leu374Pro)
Allele 2
not identified
c.331G>A; p.(Gly111Arg) c.331G>A; p.(Gly111Arg)
c.1529G>A; p.(Arg510Gln) c.1073G>A; p.(Gly358Glu)
c.1269G>A; p.(?)
c.1654G>A; p.(Val553Met)
c.721G>T; p.(Glu241*) c.1529G>A; p(Arg510Gln)
c.494G>T(p.Gly165Val)
c.1529G>A;
p. (Arg510Gln)
c.1456C>T; p(Arg486Trp) c.1436G>A; p.(Arg479His)
c.1529G>A;
p. (Arg510Gln)
c.1705C>T; p.(Arg569Trp)**
c.1706G>A; p.(Arg569Glu)
6.4 2.84 1014
4.8 2.59 343 6.6 3.79 431
9.1 5.26 37.8 5.0 2.27 1011
6.3 2.99 180 6.3 2.52 ND
6.2 3.45 198 4.1 1.79 694
8.4 3.76 627
5.4 2.18 945
7.2 3.60 181 5.6 2.86 950
ND ND ND
7.3 576
13.4 345 10.6 645
4.97 188 21.1 ND
7.1 239 10.0 696
5.5 179 9.8 657
12.4 732
13.1 876
5.5 245 12.3 719
ND ND
6.4 186
6.0 327 25-120 4.0-13.5
female
male 7.6
7.2 3.60 112 3.74 204
Table 1B. Baseline comparison to controls. PKD
HC
38.9 ± 12.8 9.12 ± 0.7 58.6 ± 22.4 2.21
(A) Clinical characteristics of pyruvate kinase deficiency (PKD) patients regarding age, sex, hemoglobin (Hb), red blood cell count (RBC), reticulocyte count (Retics), white blood cell count (WBC),platelets (Plts),treatment and genetic diagnostics.Regular transfusions are defined as ≥6 per 12 months. ND: not determined. (B) Comparison of age, Hb, Retics and time between blood withdrawal and spotting (time to dried blood spots [DBS]) between healthy controls (HC) and PKD patients.Data are presented as mean ± standard deviation,except for time to DBS which is presented as the median.
7.4-10.7 3.6-5.5
*Age and sex-dependent; **a third and rare mutation (c. 1639C>T; p(Arg547Cys)) with uncertain pathogenicity was identified in this patient.
Age (years)
Hb (mmol/L)
Retics (x109/L)
Median time to DBS (hours)
32.6 ± 17.4
6.41 ± 1.35 494.8 ± 367.5 2.33
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