Table 2.
Clinical characteristics of patients with rare ALPL variants
| Pat | Age | Sex | Symptoms | ALP [U/L] | BAP [µg/L] | PLP [µg/L] | Status | Type | References |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 45 | M | Low BMD, low-traumatic vertebral fractures, os sacrum stress fracture, clavicula pseudarthrosis, depression, reduced grip force | 62 | 12.3 | 55.7 | het | c.-81G > A | rs528218843 |
| 2 | 64 | M | Osteonecrosis | 19 | 3.1 | 51.5 | het |
c.286G > C (p.Ala96Pro) |
– |
| 3 | 75 | F | Low BMD, low-traumatic wrist fracture | 43 | 8.2 | 107.2 | het |
c.436G > A (p.Glu146Lys) |
[8, 47], SESEP |
| 4a | 53 | F | Severe caries, migraine, depression, tendinopathy | 32 | 2.8 | 15.8 | het |
c.565_575delinsAG (p.Asp189_Met192delinsArg) |
SESEP |
| 5a | 27 | F | Cephalgia, reduced grip force | 30 | 4.7 | 12.6 | het | ||
| 6a | 53 | F | Low BMD, tooth loss, periodontitis, tooth hypomineralization, narrow jaw, myalgia | 30 | 4.8 | 19.0 | het | ||
| 7 | 48 | M | Vertebral bone marrow edema, migraine, reduced grip force | 23 | 2.7 | 40.3 | het | ||
| 8 | 43 | F | Tooth extraction, scoliosis, chronic pain, cephalgia | 25 | 2.6 | 34.7 | het |
c.625A > T (p.Met209Leu) |
[13], SESEP |
| 9 | 65 | F | Low BMD, proximal femur fracture, arthralgia, myalgia | 41 | 4.7 | 30.1 | het |
c.661G > T (p.Gly221Cys) |
– |
| 10 | 37 | F | Periodontitis, depression, migraine, fatigue, myalgia, reduced grip force | 30 | 6.5 | 42.1 | het |
c.818C > T (p.Thr273Met) |
rs148405563 |
| 11 | 55 | F | Metatarsal stress fractures, tooth loss, depression, migraine, myalgia, fatigue | 38 | 4.2 | 19.2 | het |
c.876_882delinsT (p.Gly293_Asp294d) |
[33], SESEP |
| 12 | 49 | F | Stress fractures, periodontitis, cephalgia, depression, myalgia, fatigue, reduced grip force | 25 | 4.5 | 49.4 | het |
c.1004G > C (p.Arg335Thr) |
SESEP |
| 13b | 57 | F | Low BMD, myalgia, tendinosis calcarea, reduced grip force | 23 | 4.2 | 39.6 | het |
c.1023T > A (p.His341Gln) |
rs1280398041 |
| 14b | 61 | F | Low BMD, poor dentition, myalgia, reduced grip force | 20 | 2.5 | 50.9 | het | ||
| 15 | 58 | F | Pseudarthrosis, tooth hypomineralization, migraine, myalgia, tendinosis calcarea, reduced grip force | 20 | 1.9 | 37.4 | het |
c.1171dupC (p.Arg391Profs*14) |
rs751404811 |
| 16 | 35 | M | Atraumatic tibia fracture, low BMD, severe caries, dental malposition, depression, panic attacks, reduced grip force | 45 | 5.5 | 22.1 | het |
c.1310-544_1548del (p.His438Leufs) |
[35], SESEP |
| 17 | 69 | F | Low BMD, bone marrow edema proximal tibia, cephalgia, arthralgia, myalgia, reduced grip force | 40 | 3.2 | 32.2 | het |
c.1558_1559del (p.Leu520fs) |
rs1553415164 |
References included literature and the following databases: ALPL Gene Mutation Database (SESEP) and Single Nucleotide Polymorphism Database (dbSNP) by the National Center for Biotechnology Information (NCBI)
M male, F female, BMD bone mineral density, ALP alkaline phosphatase (reference range: male 40–129 U/l, female 35–104 U/l), BAP bone-specific alkaline phosphatase (reference range: male 5.2–24.4 µg/l, female ≤ 45 years 4.9–26.6 µg/l, female > 45 years 5.5–22.9 µg/l), PLP pyridoxal 5′-phosphate (reference range: < 18.5 µg/l); het heterozygote)
aMembers of the same family, two sisters and one daughter
bMembers of the same family, two sisters