Hypophosphatasia: A Case Report

Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase activity.The prevalence of severe forms of the disease has been estimated at 1/100 000. The symptoms are highly variable in their clinical expression, which ranges from stillbirth without mineralized bone to early loss of teeth without bone symptoms. The diagnosis is based on laboratory assays and DNA sequencing of the ALPL gene. Serum alkaline phosphatase (AP) activity is markedly reduced in hypophosphatasia, while urinary phosphoethanolamine (PEA) is increased. By using sequencing, approximately 95% of mutations are detected in severe (perinatal and infantile) hypophosphatasia.) Over the past 10 years, great progress has been made in understanding the structure of tissue non-specific alkaline phosphatas.The classic oral features of hypophosphatasia , namely, premature tooth loss , with premature shedding of teeth and aplasia of cementum,and large pulp spaces, were found in a young adult woman with bone and joint pains. Several with dental abnormalities such as abnormal enamel, dentin, or cementum formation, decreased mandibular bone density. This phenomenon has not been observed in the permanent dentition, whereas abnormally large pulp chambers, so-called"shell-teeth", are seen in both the primary and the permanent dentition. The absence of serious symptoms of gingivitis is a typical sign of hypophosphatasia. It is suggested, therefore, that premature exfoliation of teeth in patients with hypophosphatasia is due to aplasia of cementum. The effect of this aplasia is to deprive the tooth of its normal periodontal membrane attachment which leads to spontaneous exfoliation of the tooth.The clinical expression of the disease is highly variable, Accordingly, Six clinical forms are currently recognized, depending on the age at diagnosis and the severity of the symptoms: perinatal lethal; infantile; childhood; adult;odontohypophosphatasia; and, more recently described perinatal benign. In the perinatal lethal form of hypophosphatasia, Some infants survive for a few days but have respiratory complications due to hypoplastic lungs and rachitic deformities of the chest. Other symptoms include apnea, seizures and marked shortening of the long bones. Patients with the infantile form of hypophosphatasia may appear normal at birth;however, the clinical signs appear during the first 6 months of life. This form of the disease also has respiratory complications due to rachitic deformities of the chest。Premature craniosynostosis is a common finding that may result in increased intracranial pressure. Childhood hypophosphatasia is probably the most heterogeneous clinical form of Hypophosphatasia. Skeletal deformities, such as dolichocephalic skull and enlarged joints, a delay in walking, short stature and waddling gait are observed. Signs of intracranialhypertension or failure to thrive are typical. A history of fractures and bone pain usually exists as well. The adult form of hypophosphatasia presents during middle age. The first complaint may be foot pain, which is due to stress fractures of the metatarsals. Odontohypophosphatasia may affect both children and adults. It is characterized bypremature exfoliation of fully rooted primary teeth and/or severe dental caries, often not associated with abnormalities of the skeletal system.Hypophosphatasia is a rare inherited disorder in which the activity of the bone/liver/kidney or tissue nonspecific form of alkaline phosphatase (ALP) is reduced. Hypophosphatasia (HP) is an inborn error of bone metabolism transmitted predominantly as an autosomal-recessive trait. It is characterized by a reduced activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSAP) and elevated concentrations of its substrates, including pyrophosphates.This substrates is pyridoxal - 5′- phosphate , PL P; pyrophosphate , Ppi; phosphoethanolamine ,PEA.Laboratory assays, genetic counselling and testing, and radiologic imaging can confirm the diagnosis. Because symptoms are highly variable in their clinical expression, patients should be followed by a HP-experienced multidisciplinary team (paediatrician, radiologist, orthopedist, neurosurgeon, dentist). At the moment symptomatic support and treatment is most important because a causative therapy, e. g. enzyme replacement therapy, is not yet available.Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications.Case report:patient Jia*,boy,5 years old. case history:Because the visited our hospital at Apri 12th 2009.parents describe temporary teeth falling off one after another soon after eruption .at the time of pregnancy mother has no abnormalities and drug history, Denied similar genetic family history of disease and other infectious Abstract diseases, Clinical examination: General condition good, vital signs were stable. No facial abnormalities, theosophy clear, normal speech, have no problem about intelligence, walking slowly staggering gait. Limbs, weak muscle tone. body weight: 15.6kg. stature : 92cm . No limb deformity . There was no family history of such a disorder. Oral examination: Good oral hygiene, Ren quality gum pink, Probe can not get blood, Permanent tooth is not Moe , Remaining teeth: 53,54,54,63,64,65,73,74,75,83,84,85(figure1-5). Referral On marth 1th 2009: Remaining teeth: 53,54,64,65,73,74.74Ⅲ°loose. families to take account of the recent line of traditional Chinese medicine , Consciously body condition improved slightly . Laboratory Check : Biochemistry: ALP:14.8 U/L(normal:40-500 U/L),Serum calcium:2.6 mmol / L,(normal2.02～2.7 mmol / L),Serum phosphorus:1.43 mmol / L(normal0.8～1.5 mmol / L),γ- Glutamate(GGT):6 U/L,Lower than normal(8-50),Prothrombin activity(PA):116mg/L, Lower than normal(200-400). On the radiographs:oral slide plate and periapical film(figure1-7): alveolar bone has no abnormality seen , Shows the normal number of permanent tooth germ , deciduous teeth short root, root canal enlargement, camera pulpi and lumens enlarge , root canal wall thinness .The apical zone of Loose teeth has lower density . The X rail film of limbs bone has no abnormality seen in bone joint,but Osteoporosis bone density slightly(figure8-9). The head CT has no abnormality seen (figure10-13). Diagnosis: Hypophosphatasia. Therapy: Symptomatic treatment: Selective removal of excessive loosening of the deciduous teeth, Oral hygiene instruction.