Dental effects of enzyme replacement therapy in case of childhood-type hypophosphatasia

Background Hypophosphatasia (HPP), a skeletal disease characterized by hypomineralization of bone and teeth, is caused by an ALPL gene mutation that leads to low activity of the tissue non-specific alkaline phosphatase enzyme. Although enzyme replacement therapy (ERT) was recently introduced for affected patients, no known studies have been reported regarding its dental effects related to permanent teeth and jaw bones. In the present study, we examined the dental effects of ERT in a case of childhood-type hypophosphatasia, including panoramic radiography findings used to estimate the dental age of permanent teeth and mandibular bone density. Furthermore, the effects of that therapy on the periodontal condition of the patient were evaluated by comparing periodontal pocket depth before and after initiation. Case presentation An 11-year-1-month-old boy was referred to our clinic for consultation regarding oral management. Two primary incisors had spontaneously exfoliated at 1 year 8 months old and he had been diagnosed with childhood-type HPP at the age of 2 years 2 months. Obvious symptoms were localized in the dental region at the time of diagnosis, though later extended to other parts of the body such as bone pain. ERT was started at 11 years 7 months of age, after which bone pain disappeared, and motor functions and activities of daily living improved. We estimated dental age based on tooth development stage. The age gap between chronological and dental ages was expanded before treatment, and then showed a constant decrease after ERT initiation and finally disappeared. The index for mandibular bone density (mandibular cortical width / length from mesial buccal cusp to apex of first molar) was increased after ERT initiation. Furthermore, the periodontal condition for all teeth except those exfoliated was stable after starting therapy. Conclusions ERT resulted in improved tooth and mandibular bone mineralization, with notably good effects on teeth under formation. Acceleration of mineralization of roots associated with erupting teeth leads to stabilization of the periodontal condition. We concluded that ERT contributed to the improved dental condition seen in this patient.

An 88.8-kb Novel Deletion of 19q13.2 Encompassing the ATP1A3Gene Detected by Array CGH in a Patient with Delayed Psychomotor Development, Generalized Hypotonia and Macrocephaly

Many neurodevelopmental disorders are caused by the presence of CNVs. Chromosome microarray technology is widely used to accurately detect CNVs. We report the case of a male, aged 3 years, presenting with delayed psychomotor development, generalized hypotonia, encephalopathy, delayed myelination in the central nervous system, and poor motor coordination. The array CGH revealed an interstitial deletion of chromosome 19q13.2 with a size of 88.8 kb involving 3 OMIM genes: <i>RABAC1</i>, <i>ARHGEF1</i>, and <i>ATP1A3</i>. Heterozygous mutations in the <i>ATP1A3</i> gene are associated with delayed psychomotor development, alternating hemiplegia of childhood type 2 (AHC2), dystonia type 12, and cerebellarataxia-areflexia–pes cavus-optic atrophy-sensorineural hearing loss syndrome, also called CAPOS syndrome. The phenotypic expression of partial <i>ATP1A3</i> deletion is, however, poorly described in the literature. The deletion was confirmed by MLPA, and we identified a hitherto undescribed novel deletion of exons 3b–21 of the <i>ATP1A3</i> gene. Our data suggest that the deletion of the <i>ATP1A3</i> gene is a causative factor of the AHC2 phenotype in the patient.

Case Report: Multisystem Langerhans Cell Histiocytosis (LCH) and Myelodysplastic Syndrome (MDS) in a 13-Month-Old Female

<p>Langerhans Cell Histiocytosis or LCH and Myelodysplastic syndrome or MDS in children are rare diseases. It is estimated to be 1 to 4 cases per 1 million population and less than 5% of hematologic cases. MDS in LCH can occur due to genetic predisposition, impaired cytokine production, or secondary to chemotherapy. The article reported a patient case of a 13-month-old female who came to hospital with paleness since two weeks before admission. The patient also experienced skin redness, abdominal distention, and weight loss. From the physical examination, anemia, maculopapular rash, and hepatosplenomegaly were obtained. From the laboratory test, anemia of hypochromic anisopoikilocytosis, monocytosis, thrombocytopenia, and hypoalbuminemia were obtained. On examination of bone marrow aspiration, MDS with Refractory Cytopenia of Childhood type or RCC was obtained. Positive results confirmed the diagnosis of Langerhans Cell Histiocytosis on CD68 and S100 in histopathological examinations.</p>