Table 1.

Key characteristics of 9 adult patients with HPP.

Case	Age (y)/gender	Early dental issues	Age of first fracture (y)	Fractures (no.)	Other bone issues	Other disease burden	Genotypea	Inheritance	Family history of HPP	Diagnosing specialty	Age at diagnosis (y)
1	35/male	Persistent primary teeth, requiring extraction	No fractures	0	Chronic back pain; bone pain	Chronic fatigue; difficulty sleeping, joint pain	c.335_340dupACCGCC (p.Gly112_Thr113dup2) in exon 5	AD	Sister and niece: c.335_340dupACCGCC (p.Gly112_Thr113dup2). Father and paternal uncle with symptoms without confirmed diagnosis	Unknown	33, due to positive family history
2	70/female	No dental complaints	26	21	Delayed healing of fractures; bone pain	Feeding difficulty	c.1328C > T (p.A443V) in exon 12	AD	Unknown	Rheumatology	53
3	32/male	Loss of all primary teeth starting at 8 months	17	2	–	Unusual gait	c.1133A > T (p.D378V) in exon 10	AD	Asymptomatic 2-year-old son: confirmed familial mutation. Mother, sister, brother, and a maternal aunt with symptoms without diagnosis. Confirmed HPP	Endocrinology	3
4	58/female	Primary tooth loss at age 3 years	14	7	Bone pain; abnormally shaped head; genu valgum	Unusual gait; delayed talking; muscle pain and weakness; joint pain and swelling	c.1133A > T (p.D378V) in exon 10	AD	Niece: prenatally diagnosed HPP. Son of a different niece: confirmed HPP	Endocrinology	23, due to positive family history
5	62/female	Loss of all front primary teeth at 13 months	8	7	Bone pain	Unusual gait	c.1133A > T (p.D378V) in exon 10	AD	Son and granddaughter through the son: confirmed HPP	Unknown	53
6	63/female	Primary tooth loss at age 3 years	19	9	Bone pain	Difficulty eating/swallowing	c.526G > A (p.A176T) in exon 6/c.648 + 1G > A in IVS6	AR	Sister (Case 7): confirmed with HPP	Endocrinology	57
7	50/female	Primary tooth loss before age 2; absent primary teeth	18	19	Bone pain	Unusual gait; joint pain/swelling; long QT; hypokalemia	c.526G > A (p.A176T) in exon 6/c.648 + 1G > A in IVS6	AR	Sister (Case 6): extractions of all of her teeth; metatarsal stress fractures	Endocrinology	41
8	60/female	Primary tooth loss at age 3 years	12	25	Bone pain	Unusual gait; joint hypermobility; joint dislocation/pain; muscle pain/weakness, carpal tunnel surgery, pneumonia	c.571G > A (p.E191K) in exon 6/c.661G > C (p.G221R) in exon 7	AR	Brother: premature tooth loss	Endocrinology	55
9	59/female	Primary tooth loss at 3–4 years	6	6	Club foot; bone pain	Unusual gait; gout	c.571G > A (p.E191K) in exon 6/c.1250A > G (p.N417S) in exon 11	AR	Unknown	Unknown	4

AD, autosomal dominant; AR, autosomal recessive.

^aMutations shown are to the ALPL gene; Genbank accession number NG_008940.1.