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Articles » Skeletal » Hypophosphatasia
1999-05-05-12 Hypophosphatasia © Jeanty


Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Definition: Anomaly due to defective bone mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase with 3 subtypes. A lethal type 1 with prenatal manifestations of short demineralized long bones, craniosynostosis and neonatal hypercalcemia; a type 2 with rickets-like skeletal changes, fractures and premature loss of teeth; and a type 3 with only metabolic anomalies detected on biochemical screening.

Synonyms: Phosphoethanolaminuria.

Incidence: Rare.

Etiology: Autosomal recessive. Carriers can be recognized by their low levels of serum alkaline phosphatase[1] and urinary phosphoethanolamine

Recurrence risk: 25%.

Diagnosis: The diagnosis should be suspected in fetus with micromelia, and demineralization of the bones. Spurs have been diagnosed postnatally that might be typical. These occur along the midshaft of long bones and at the knees and elbows[2],[3],[4].

Pathogenesis: Anomaly of tissue-nonspecific alkaline phosphatase (TNSALP) gene.

Genetic anomaly: The type 1 and type 2 are different disorders. There are numerous variant tissue-nonspecific alkaline phosphatase genes[5].

Associated anomalies: See definition.

Differential diagnosis: Hypophosphatasia is probably indistinguishable on ultrasound criteria only from Osteogenesis imperfecta Type II and Achondrogenesis type IA.

Prognosis: Lethal for the Type 1.

Management: In suspected fetus (25% recurrence risk) termination of the pregnancy can be offered.


[1] Rathbun, J. C.; MacDonald, J. W.; Robinson, H. M. C.; Wanklin, J. M. : Hypophosphatasia: a genetic study. Arch. Dis. Child. 36: 540-542, 1961.

[2] Goldstein, D. J.; Nichols, W. C.; Mirkin, L. D. : Short-limbed osteochondrodysplasia with osteochondral spurs of knee and elbow joints (spur-limbed dwarfism). Dysmorph. Clin. Genet. 1: 12-16, 1987.

[3] Spranger, J. : "Spur-limbed" dwarfism identified as hypophosphatasia. (Letter) Dysmorph. Clin. Genet. 2: 123 only, 1988.

[4] Vandevijver, N.; De Die-Smulders, C. E. M.; Offermans, J. P. M.; Van Der Linden, E. S.; Arends, J. W.; Sastrowijoto, S. H.; Moerman, P.; Fryns, J. P. : Lethal hypophosphatasia, spur type: case report and fetopathological study. Genet. Counsel. 9: 205-209, 1998.

[5] Mornet E, Taillandier A, Peyramaure S, Kaper F, Muller F, Brenner R, Bussiere P, Freisinger P, Godard J, Le Merrer M, Oury JF, Plauchu H, Puddu R, Rival JM, Superti-Furga A, Touraine RL, Serre JL, Simon-Bouy B: Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia. Eur J Hum Genet 1998 Jul-Aug;6(4):308-14

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