Table 5.
Summary of clinical, laboratory, and genetic findings of patients with hexokinase deficiency.
| Reference | Age (Years) | Sex | Symptoms | Hb (g/dL) | Reticulocytes (%) | Total Bilirubin | Red Cell HK Activity | Other Procedures | Genetic Testing |
|---|---|---|---|---|---|---|---|---|---|
| Valentine WN et al., 1967 [9] |
0 (5 months) | F | pallor/jaundice, hepatomegaly, splenomegaly | 9.4 | 13 | N/A | 63% | blood transfusions, splenectomy | N/A |
| Keitt AS et al., 1969 [10] | 38 | F | jaundice, mild anemia, splenomegaly | N/A | 6.1–13 | N/A | 79% | splenectomy | N/A |
| K Moser et al., 1970 [11] | 22 | M | No data available | N/A | 1.7–6.3 | N/A | 49% | N/A | N/A |
| Necheles TF et al., 1970 [12] | 2 | M | severe HA | 6.5 | 5 | N/A | 75% | splenectomy | N/A |
| Goebel KM et al., 1972 [13] | 28 | F | paleness, no hepatosplenomega-ly | 8.5–9.6 | 2 | N/A | 0.59 U/gHb | N/A | |
| Semenuk M et al., 1975 [14] | N/A | ||||||||
| Rijksen G et al., 1978 [15] | 30 | F | chronic hemolysis | 11.3 | 39 | N/A | 0.7 U/gHb | blood transfusions, splenectomy | N/A |
| Board PG et al., 1978 [16] | 2 | M | anemia, cholelithiasis, neonatal jaundice, hepatomegaly, splenomegaly | 8.6–9.4 | 6.7–8.5 | 6.1 | 0.65 U/gHb | N/A | N/A |
| Beutler E et al., 1978 [17] | 11 | F | fatigue, mild chronic HA | 11.6–12.2 | 5.1–7.4 | 1 | 0.83 U/gHb | N/A | N/A |
| Gilsanz F et al., 1978 [18] | 9 | F | anemia, jaundice, mild mental retardation | 8.7–9.5 | 10.2–16.4 | 5.3 | 68% | N/A | N/A |
| Siimes MA et al., 1979 [19] | 1 | F | anemia | 7–9.2 | 3.1–8.1 | N/A | 48% | N/A | N/A |
| Newman P et al., 1970 [20] | 19 | M | fatigue, jaundice, splenomegaly, abdominal discomfort, | 13.8 | 33 | 37 | 0.62 U/gHb | N/A | N/A |
| Paglia DE et al., 1981 [21] | 7 | M | anemia, jaundice, hepatomegaly, splenomegaly | 9.7 | 3.6–8.4 | 8.1 | 70% | blood transfusion | |
| Rijksen G et al., 1983 [22] | 19 | F | neonatal jaundice, severe HA | 9.8 | 50 | N/A | 25% | splenectomy | homozygous c.2039C>G (Thr680Ser) missense mutation in HK1 |
| Magnani M et al., 1985 [23] | 27 | F | anemia, hepatomegaly, splenomegaly, sclera jaundice, fatigue | 5.3 | 1 | 0.5 | 0.87 U/gHb | blood transfusions, splenectomy | |
| Magnani M et al., 1985 [24] | 1 | M | generalized convulsions, hepatomegaly, splenomegaly, psychomotor retardation | 11.6 | 3 | 0.3 | 45% | blood transfusions, | |
| Kanno H et al., 1997 [25] | 29 weeks (GA) | F | IUGR fetus with severe HA, periventricular leucomalacia | 3.7 | 42 | N/A | 17% | decease | |
| de Vooght KM et al., 2009 [26] | 33 | M | jaundice, fatigue, inability to concentrate, splenomegaly | 8.8 | 79 | 73 | 0.79 U/gHb | N/A | −193A>G mutation in the erythroid-specific promoter of HK1 and exon 3 c.278G>A missense mutation |
| Sajad Khazal et al., 2016 [27] | 4 | M | hydrops fetalis, severe anemia | 4.5–9 | N/A | N/A | 0.7 U/gHb | regular blood transfusions, splenectomy, bone marrow transplant | homozygous nucleotide substitution in the first nucleotide of exon 13 of the HK 1 gene |
| Koralkova P et al., 2016 [28] | 2 | M | severe hemolysis | 7.9 | 8.8 | 54 | 0.64 U/gHb | blood transfusions | heterozygous for mutations c.−193A N G and c.873-2A N G |
| 4 | M | compensated HA with no clinical symptoms | 9.5 | 6.2 | 62 | 0.58 U/gHb | N/A | heterozygous for mutations c.−193A N G and c.873-2A N G | |
| 8 months | M | severe HA, psychomotor retardation, secondary epilepsy (result of hypoxia and bleeding during delivery) | 7.4 | 6.3 | 120 | 0.71 U/gHb | blood transfusions | homozygous for the p.(Arg93Gln) mutation | |
| 2 | M | severe HA | 8.6 | 4.7 | 124 | 1.14 U/gHb | blood transfusions | c.2599C N T p.(His867Tyr) | |
| 22 | M | jaundice | 16 | 6.0 | 24 | 0.65 U/gHb | Gilbert’s syndrome | heterozygous for the p.(Thr600Met) mutation | |
| 12 | F | mild hemolysis | 13.5 | 3.1 | 100 | 0.37 U/gHb | Gilbert’s syndrome | heterozygous for the c.493-1G N A mutation | |
| 12 | F | asymptomatic, mild methemoglobinem-ia | 13.7 | 1.9 | 17.6 | 0.33 U/gHb | G6P deficiency | heterozygous c.278A N G p.(Arg93Gln), homozygous for a mutation in G6PD: c.477G N C p.(Met159Ile) | |
| Sonaye Ruhi et al., 2018 [29] | 21 | F | vomiting, loose motion, yellowish sclera, hepatomegaly, splenomegaly | 6.7 | N/A | 12.58 | N/A | blood transfusion | N/A |
| Manu Jamwal et al., 2019 [30] | 9 months | M | severe anemia, jaundice, delayed milestones | 4.7 | N/A | N/A | N/A | several blood transfusions starting with an exchange transfusion at day 4 of life, death at age 1 | homozygous nonsense variant NM_033496.2:c34C>T, p.Arg12Ter, in exon 1 of HK1 |
| Rashmi Dongerdiye et al., 2021 [31] | 4 | F | severe anemia, developmental delay | 3.5 | N/A | N/A | N/A | regular blood transfusions | homozygous variant in HK gene c.2714C>A (p.Thr905Lys) |
| Sasaki E et al., 2022 [32] | two siblings and one cousin (dizygotic twin I) | deceased, additional malformations coexistent 16p13.11 microdeletion syndrome | N/A | N/A | N/A | N/A | N/A | homozygous c.278G>A p(Arg93Gln) in exon 3 of HK 1 | |
| HA, developmental delay, epilepsy, microcephaly, white matter atrophy, recurrent apnoeic episodes | N/A | N/A | N/A | N/A | N/A | ||||
| N/A | N/A | N/A | N/A | N/A | |||||
| half-brother | HA, developmental delay, white matter atrophy | N/A | N/A | N/A | N/A | N/A | died without genetic testing | ||
| EM Ukonmaanaho et al., 2024 [33] | 3 months | F | severe HA | 6.7 | 7.3 | 33 | 1.1 U/gHb | blood transfusions, HSCT planned | homozygous for the HK1 variant c.2599C>T, p.(His867Tyr) |
| 30 | M | Mild chronic HA, splenomegaly | 12.1 | 4.6 | 103 | 0.8 U/gHb | splenectomy | heterozygous for the HK1 variant c.2599C>T, p.(His867Tyr) and c.-193A>G | |
| 37 | M | Mild chronic HA, splenomegaly | 15.9 | 0.7 | 14 | 0.52 U/gHb | cholecystectomy | heterozygous for the HK1 variants c.2361_2362del, p.(Gln788Aspfs*4) and c.-193A>G | |
| 26 | M | Cholelithiasis, compensated hemolysis | 11.9 | 3.9 | 175 | N/A | N/A | heterozygous for the HK1 variants c.372+1G>A and c.-193A>G | |