Adult hypophosphatasia without apparent skeletal disease: “odontohypophosphatasia“ in four heterozygote members of a family

Abstract

Twenty members of a family with adult hypophosphatasia were examined clinically and biochemically. Severe caries causing early loss of permanent teeth was the only clinical symptom which could be attributed to hypophosphatasia. None of them had a history of defective bone mineralization, rachitic skeletal alterations, and recurrent pseudofractures or fractures. An iliac crest bone biopsy of the proposita showed a normal finding corresponding to the age of the patient. Four family members in two subsequent generations were affected, thus suggesting an autosomal dominant inheritance. Their serum and leukocyte alkaline phosphatases were reduced. The phosphoethanolamine (PEA) excretion in the urine was increased to a level which suggests a heterozygote state. The serum alkaline phosphatase activity could be ascribed to the liver isoenzyme fraction. This was shown by polyacrylamide electrophoresis, by inhibition studies with organ-specific inhibitors, heat inactivation, inhibition by antibodies, and treatment with neuraminidase. The proposita had an unexplained, diffuse fatty infiltration of the liver. Thus, not only alterations of bone but also of liver metabolism in hypophosphatasia should be considered. The variety of adult hypophosphatasia described in this paper is characterized by the lack of severe bone abnormalities, the apparently autosomal dominant inheritance, and the reduction of bone and intestinal isoenzyme in the serum. Our study suggests that hypophosphatasia is a heterogeneous disorder which includes both severe and clinically mild forms.

Importance of deletion of T at nucleotide 1559 in the tissue-nonspecific alkaline phosphatase gene in Japanese patients with hypophosphatasia

“…In addition, the possibility of dominant inheritance cannot be excluded. Nevertheless, the dominant inherited cases previously reported exhibited milder phenotypes [26,27]. Therefore, it seems unlikely that case 2 and case 4 carried only one mutation.…”

Clinical utility gene card for: Hypophosphatasia – update 2013

“…1 A number of missense mutations exhibit a dominant-negative effect 2-5 explaining dominant inheritance of mild forms of the disease. [6][7][8] …”

Clinical and Radiographic Findings in Adults With Persistent Hypophosphatasemia

“…Moderate adult forms in that study included adult survivors of childhood HPP, those diagnosed in adulthood, and those with odontohypophosphatasia only. Nevertheless, the prevalence and clinical spectrum of adult HPP is likely still not fully appreciated because the condition may be asymptomatic or be misdiagnosed as idiopathic pseudogout or more likely, postmenopausal osteoporosis . Classic adult HPP is characterized by premature dental loss, extraskeletal calcification, chondrocalcinosis, and slowly healing metatarsal and subtrochanteric femur stress fractures .…”