Hypophosphatasia is a rare inborn disease of metabolism. This paper reviewed its pathogenesis, forms, clinical manifestations, differential diagnosis,treatment and prognosis. Here a case of neonatal hypophosphatasia is reported. This baby was female (30 minutes old). Prenatal ultrasound showed disproportionate biparietal diameter and long bones of limbs in the baby. After birth, she presented with obvious craniomalacia, respiratory distress and cyanosis. Serum alkaline phosphatase level was significantly reduced. Both X-ray and autopsy showed extremely insufficient skeletal mineralization. Four days later she died of respiratory failure.
Diagnosis, Differential ; Female ; Humans ; Hypophosphatasia ; classification ; etiology ; therapy ; Infant, Newborn

Hypophosphatasia is a clinically heterogeneous inheritable disorder characterized by defective bone mineralization and the deficiency of serum and tissue liver/bone/kidney alkaline phosphatase activities. Due to the mineralization defect of the bones, various skeletal findings can be radiologically observed in hypophosphatasia. Bowing and Bowdler spurs of long bones are the characteristic findings. The Bowdler spurs reported on in the previous pertinent literature were observed in the perinatal aged patients and these lesions have rarely involved adolescents. We herein report on a 14-year-old girl with fibular Bowdler spurs.
Adolescent ; Bone Diseases/pathology/radiography ; Diagnosis, Differential ; Female ; Fibula/pathology/*radiography ; Humans ; Hypophosphatasia/pathology/*radiography

OBJECTIVE: To explore the genetic basis for a girl featuring bone and tooth mineralization disorder, premature deciduous teeth, rickets and short stature. METHODS: Genomic DNA was extracted and subjected to high-throughput whole exome sequencing. Suspected variants were confirmed by Sanger sequencing. Impact of potential variants was analyzed with bioinformatic software. RESULTS: The child was found to carry compound heterozygous missense variants of the ALPL gene, including c.1130C>T (p.A377V), a known pathogenic mutation inherited from her father, and c.1300G>A (p.V434M) inherited from her mother, which was unreported previously and predicted to be likely pathogenic based on standards and guidelines from the American College of Medical Genetics and Genomics (PM2+PM5+PP3+PP4). CONCLUSION The compound heterozygous variants of c.1130C>T (p.Ala377Val) and c.1300G>A (p.Val434Met) of the ALPL gene probably underlay the disease in this child. Above finding has enriched the spectrum of ALPL gene variants.
Alkaline Phosphatase ; Child ; Female ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Hypophosphatasia/genetics* ; Mutation ; Whole Exome Sequencing

This article reported the clinical features of one child with infantile hypophosphatasia (HPP) and his pedigree information. The proband was a 5-month-old boy with multiple skeletal dysplasia (koilosternia, bending deformity of both radii, and knock-knee deformity of both knees), feeding difficulty, reduction in body weight, developmental delay, recurrent pneumonia and respiratory failure, and a significant reduction in blood alkaline phosphatase. Among his parents, sister, uncle, and aunt (other family members did not cooperate with us in the examination), his parents and aunt had a slight reduction in alkaline phosphatase and his aunt had scoliosis; there were no other clinical phenotypes or abnormal laboratory testing results. His ALPL gene mutation came from c.228delG mutation in his mother and c.407G>A compound heterozygous mutation in his father. His aunt carried c.228delG mutation. The c.407G>A mutation had been reported as the pathogenic mutation of HPP, and c.228delG mutation was a novel pathogenic mutation. Hypophosphatasia is caused by ALPL gene mutation, and ALPL gene detection is an effective diagnostic method. This study expands the mutation spectrum of ALPL gene and provides a theoretical basis for genetic diagnosis of this disease.
Alkaline Phosphatase ; genetics ; Carrier Proteins ; chemistry ; Female ; Heterozygote ; Humans ; Hypophosphatasia ; etiology ; genetics ; Infant ; Male ; Mutation ; Pedigree

We have detailed our experiences on 6 cases of neonatal lethal short- limbed dwarfism and reviewed thearticles. They include, achondrogenesis, thanatophoric dysplasia, asphsiating thoracic dysplasia, osteogenesisimperfecta congenita, and hypophosphatasia lethalis. Five babies were born alive but died soon after birth and onewas a stillbirth. The main cause of failure to thrive was respiratory insufficiency. Each case was having quitecharacteristic radiologic findings, even if the genearl appearances were similar to the achondroplasts clinically.Precise diagnosis is very important for genetic counselling of the parents and alarm to them the possibility ofbone dysplasias to the next offsprings. For this purpose, the radiologists play major role for the correctdiagnosis. We stress that when the baby is born with short-limbed dwarfism, whole body radiogram should be takenincluding lateral view and postmortem radiogram is also very precious.
Diagnosis ; Dwarfism ; Extremities ; Failure to Thrive ; Humans ; Hypophosphatasia ; Parents ; Parturition ; Respiratory Insufficiency ; Stillbirth ; Thanatophoric Dysplasia

PURPOSE: Calcium pyrophosphate dihydrate crystal deposition disease(CPPD) is a disease of the elderly and extremely rare in young individuals. If young people develop CPPD crystal deposition disease, it may be associated with metabolic diseases, such as hemochromatosis, hyperparathyroidism, hypophosphatasia, hypomagnesemia, Wilson's disease, hypothyroidism, and gout. MATERIALS AND METHODS: Therefore, in young-onset CPPD crystal deposition disease, an investigation of any predisposing metabolic conditions is warranted. CONCLUSION: We report a case of a young female patient who presented with idiopathic CPPD crystal deposition disease at 25 years of age.
Aged ; Calcium ; Calcium Pyrophosphate ; Chondrocalcinosis ; Diphosphates ; Female ; Gout ; Hemochromatosis ; Hepatolenticular Degeneration ; Humans ; Hyperparathyroidism ; Hypophosphatasia ; Hypothyroidism ; Metabolic Diseases

Calcium pyrophosphate dihydrate (CPPD) deposition disease is a heterogeneous group of diseases with CPPD crystal deposition. Aging is the most common risk factor for CPPD deposition, followed by osteoarthritis and previous injury. Occasionally, CPPD depositions are associated with familial predisposition and metabolic diseases, including hemochromatosis, primary hyperparathyroidism, hypophosphatasia, and hypomagnesemia. CPPD deposition diseases associated with primary hyperparathyroidism in Koreans have rarely been reported. Thus, we report a case of a relatively young female patient with CPPD deposition disease associated with primary hyperparathyroidism, which was diagnosed through a polarized microscopic examination of the synovial fluid and a subtotal parathyroidectomy.
Aging ; Calcium Pyrophosphate ; Chondrocalcinosis* ; Female ; Hemochromatosis ; Humans ; Hyperparathyroidism, Primary* ; Hypophosphatasia ; Metabolic Diseases ; Osteoarthritis ; Parathyroidectomy ; Risk Factors ; Synovial Fluid

This paper summarizes the clinical features, causative genes and treatment progress of patients with rickets-like genetic diseases, including X-linked hypophosphatemic rickets (XLH), hypophosphatasia, achondroplasia, vitamin D-dependent rickets, pycnodysostosis and ectodermal dysplasia, who visited the pediatric or child health clinic due to the symptoms of rickets, including bow legs, delayed closure of the anterior fontanelle, and sparse hair. Children with XLH usually go to hospital for bow legs and short stature, and biochemical evaluation reveals significantly low serum phosphorus so it is easily diagnosed. This disease is treated using phosphate mixture and 1,25(OH)2D3, which is different from the treatment of nutritional vitamin D deficiency rickets. Hypophosphatasia is characterized by a significant decrease in serum alkaline phosphatase, as well as normal serum calcium and phosphorus. The disease is caused by mutations in TNSALP gene. Patients with achondroplasia show short-limbed dwarfism and special face in addition to bow legs, but with normal serum calcium, phosphorus and alkaline phosphatase. Bone X-ray and FGFR3 gene test contribute to the diagnosis. Vitamin D-dependent rickets is an autosomal recessive disease, and active vitamin D supplement is effective in treatment of the disease. Patients with pycnodysostosis may be first seen at hospital because of large anterior fontanelle; in addition, they also show obtuse mandibular angle, dental abnormalities and dysplastic nails, which are caused by mutations in TSK gene. Children with ectodermal dysplasia may see a doctor for sparse hair, and they are easily misdiagnosed with nutritional vitamin D deficiency rickets. Ectodermal dysplasia is related to EDA, EDAR, EDARADD and WNT 10A genes.
Achondroplasia ; genetics ; therapy ; Ectodermal Dysplasia ; genetics ; therapy ; Familial Hypophosphatemic Rickets ; genetics ; therapy ; Humans ; Hypophosphatasia ; genetics ; therapy ; Pycnodysostosis ; genetics ; therapy

OBJECTIVETo screen potential mutations of PHEX gene in a family featuring hypophosphatemic rickets in order to confirm the molecular diagnosis and pathogenetic mechanism.

METHODSGenomic DNA was extracted from peripheral venous blood samples. DNA sequence of PHEX gene was derived from UCSC database, and primers for its coding region were designed with Primer premier 5.0. Potential mutations were detected with PCR amplification and DNA sequence analysis.

RESUTLSA mutation was identified in intron 6 of the PHEX gene in the proband and his mother.

CONCLUSIONThe c.732+1G>T mutation underlies the hypophosphatemic rickets in this family.

Adult ; Base Sequence ; Child ; Female ; Humans ; Hypophosphatasia ; enzymology ; genetics ; Introns ; Male ; Molecular Sequence Data ; Mutation ; PHEX Phosphate Regulating Neutral Endopeptidase ; genetics ; Pedigree

Congenital hypophosphatasia is a rare fatal skeletal dysplasia. Antenatal determinants of Epub ahead of print lethality include small thoracic circumference with pulmonary hypoplasia and severe micromelia. These features were present in the fetus of a 25-year-old female who came for an anomaly scan in her second trimester of pregnancy. Additional findings of generalized demineralization and osteochondral spurs led to the diagnosis of hypophosphatasia congenita. The pregnancy was terminated, and the findings were confirmed on autopsy. Common differential diagnoses with clues to diagnose the above mentioned condition have been discussed here. Early and accurate detection of this medical condition is important as no treatment has been established for this condition. Therefore, antenatal ultrasonography helps in diagnosing and decision making with respect to the current pregnancy and lays the foundation for the genetic counseling of the couple.
Adult ; Autopsy ; Decision Making ; Diagnosis ; Diagnosis, Differential ; Exostoses ; Female ; Fetus ; Genetic Counseling ; Humans ; Hypophosphatasia* ; Pregnancy ; Pregnancy Trimester, Second ; Prenatal Diagnosis* ; Ultrasonography* ; Ultrasonography, Prenatal