scholarly journals Two Novel Mutations in the ALPL gene of Unrelated Chinese Children with Hypophosphatasia: Case Reports and Literature Review

2019 ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective: Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation: Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G>C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G>C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions: In this study, six mutations in the ALPL gene were found in four Chinese HPP patients. Two of which were novel: c.359G>C in exon 5 and c.1017dupG in exon 10. Our results strongly indicated that the novel mutation c.359G>C might be disease-causing and associated with severe infantile form of HPP.

scholarly journals Two novel mutations in the ALPL gene of unrelated Chinese children with Hypophosphatasia: case reports and literature review

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G > C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G > C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions In this study, six mutations in the ALPL gene were found in four Chinese HPP patients, two of which were novel: c.359G > C in exon 5 and c.1017dupG in exon 10. Our results strongly indicated that the novel mutation c.359G > C might be disease-causing and associated with severe infantile form of HPP.

scholarly journals Two Novel Mutations in the ALPL gene of Unrelated Chinese Children with Hypophosphatasia: Case Reports and Literature Review

2019 ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective: Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation: Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G>C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G>C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions: In this study, six mutations in the ALPL gene were found in four Chinese HPP patients. Two of which were novel: c.359G>C in exon 5 and c.1017dupG in exon 10. Our results strongly indicated that the novel mutation c.359G>C might be disease-causing and associated with severe infantile form of HPP.

scholarly journals Two Novel Mutations in the ALPL gene of Unrelated Chinese Children with Hypophosphatasia: Case Reports and Literature Review

2019 ◽  
Author(s):  
Xiaojian Mao ◽  
Sichi Liu ◽  
Yunting Lin ◽  
Zhen Chen ◽  
Yongxian Shao ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Case Reports ◽  
Chinese Children ◽  
Deciduous Teeth ◽  
Missense Mutations ◽  
The Novel ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Alp Activity

Abstract Objective: Hypophosphatasia (HPP) is an inherited disorder of defective skeletal mineralization caused by mutations in the ALPL gene that encodes the Tissue Non-specific Alkaline Phosphatase (TNSALP). It is subdivided into six forms depending on the age of onset: perinatal lethal, prenatal benign, infantile, childhood, adult, and odonto HPP. Among these, infantile HPP is characterized by early onset and high frequency of lethal outcome. Few studies have reported the phenotype and genetic characteristics of HPP in Chinese children. Case presentation: Three forms of HPP were identified in four unrelated patients from four different Chinese families, including one lethal infantile (patient 1), two childhood (patient 2 and 3) and one odonto HPP (patient 4). Six variants in the ALPL gene were identified, including five missense mutations and one frameshift mutation. Of which, none were reported previously in the Chinese population, and two were novel (c.359G>C: p.G120A and c.1017dupG: p.H340AfsX3). Patient 1 carrying a novel homozygous (c.359G>C) mutation showed respiratory distress and pneumonia at first day of his life. He presented nearly negligible level of serum ALP activity, overall skeletal hypominaralization and died at 3 months old. Patient 2, 3 and 4 were compound heterozygotes with decreased serum ALP activity. Patient 2 and 3 presented premature loss of deciduous teeth, muscle weakness and bone pain, whereas patient 4 had early loss of deciduous teeth only. All four pedigrees exhibited autosomal recessive pattern of inheritance. Conclusions: In this study, six mutations in the ALPL gene were found in four Chinese HPP patients. Two of which were novel: c.359G>C in exon 5 and c.1017dupG in exon 10. Our results show that the novel mutation c.359G>C is strongly indicated to be disease-causing and associated with severe infantile form of HPP.

scholarly journals Novel compound heterozygous EYS variants may be associated with arRP in a large Chinese pedigree

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chunli Wei ◽  
Ting Xiao ◽  
Jingliang Cheng ◽  
Jiewen Fu ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Gene Mutations ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
The Novel ◽  
Pathogenic Variants ◽  
Pathogenic Genes ◽  
Compound Heterozygous Variants ◽  
Normal Controls

Abstract As a genetically heterogeneous ocular dystrophy, gene mutations with autosomal recessive retinitis pigmentosa (arRP) in patients have not been well described. We aimed to detect the disease-causing genes and variants in a Chinese arRP family. In the present study, a large Chinese pedigree consisting of 31 members including a proband and another two patients was recruited; clinical examinations were conducted; next-generation sequencing using a gene panel was used for identifying pathogenic genes, and Sanger sequencing was performed for verification of mutations. Novel compound heterozygous variants c.G2504A (p.C835Y) and c.G6557A (p.G2186E) for the EYS gene were identified, which co-segregated with the clinical RP phenotypes. Sequencing of 100 ethnically matched normal controls didn’t found these mutations in EYS. Therefore, our study identified pathogenic variants in EYS that may cause arRP in this Chinese family. This is the first study to reveal the novel mutation in the EYS gene (c.G2504A, p.C835Y), extending its mutation spectrum. Thus, the EYS c.G2504A (p.C835Y) and c.G6557A (p.G2186E) variants may be the disease-causing missense mutations for RP in this large arRP family. These findings should be helpful for molecular diagnosis, genetic counseling and clinical management of arRP disease.

Alternating Hemiplegia of Childhood, neurological comorbidities, intrafamilial variability: case-reports and literature review.

2021 ◽  
Author(s):  
Piero Pavone ◽  
Xena Giada Pappalardo ◽  
Naira Mustafa ◽  
Sung Yoon Cho ◽  
Dong Kyu Jin ◽  
...  
Keyword(s):  
Literature Review ◽  
Developmental Delay ◽  
Age Of Onset ◽  
Case Reports ◽  
Epileptic Seizures ◽  
The Body ◽  
Motor Dysfunction ◽  
Missense Mutations ◽  
Alternating Hemiplegia Of Childhood ◽  
Novel Variant

Abstract BACKGROUND Alternating Hemiplegia of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months, recurrent hemiplegia of one or either sides of the body or quadriplegia. Neurological comorbidities observed in two couples of AHC affected children are here reported together with data drawn by literature review. Results of genetic analysis obtained in the probands are also discussed. Developmental delay, epilepsy, tonic or dystonic spells, nystagmus and autonomic manifestations are frequently reported. AHC is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene.CASE PRESENTATION Clinical and genetic findings of a couple of twins and a couple of siblings affected by AHC from two different Italian families were deeply examined. Intrafamilial clinical variability was shown in the present cases. A pathogenic variant rs606231437 in ATP1A3 gene was detected in twins. For the affected siblings of family 2, the genetic results showed that the older brother and the healthy father shared a novel variant of GRIN2A (c.3175T>A) gene, and two missense mutations in SCNIB (rs150721582) and KCNQ2 (rs771211103) genes. In the younger brother was found only the GRIN2A variant.CONCLUSIONS Developmental delay, epileptic seizures and motor dysfunction are features frequently associated to paroxysmal hemiplegic attacks. Hemiplegic episode is only a sign even if the most remarkable of several neurological comorbidities in AHC carriers. The comparison of molecular analysis among the four probands brings out how the genetic framework is not recurrent, but may result from an unexpected greater genetic heterogeneity.

scholarly journals Clinical and genetic characteristics of hypophosphatasia in Chinese children

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Meijuan Liu ◽  
Min Liu ◽  
Xuejun Liang ◽  
Di Wu ◽  
Wenjing Li ◽  
...  
Keyword(s):  
Serum Alkaline Phosphatase ◽  
Hot Spot ◽  
Age At Onset ◽  
Splice Junction ◽  
Chinese Children ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Genetic Characteristics ◽  
Female Ratio ◽  
Frameshift Mutations

Abstract Background Hypophosphatasia (HPP) is a rare inherited disorder, which is caused by loss-of-function mutations in the ALPL gene. HPP is a heterogeneous disease that has a wide spectrum of phenotypes. Few studies were carried out in the Chinese population with HPP, especially in children. Methods The clinical and genetic characteristics of 10 Chinese children with HPP who were referred to the Beijing Children’s Hospital were described. Previously reported HPP cases of children in China were also reviewed. Results A total of 33 cases were identified, which included 2 perinatal lethal HPP, 10 infantile HPP, 10 childhood HPP, and 11 odonto HPP. The male-to-female ratio was 24:9. The average age at onset was 0.69 years (ranged from 2 h after birth to 14 years), while the average age at clinical diagnosis was 3.87 years (ranged from 2 h after birth to 19 years). Serum alkaline phosphatase (ALP) levels were significantly decreased in patients with perinatal lethal/infantile HPP when compared with those with the mild forms of HPP childhood/odonto HPP (P < 0.01). Although serum phosphate levels were not different (P > 0.05), serum calcium levels were elevated, and serum intact parathyroid hormone levels were decreased in patients with perinatal lethal/infantile HPP in comparison with those with the childhood/odonto HPP (P all < 0.01). Genetic analyses identified 40 mutations in 31 HPP cases, including 28 missense mutations, 9 frameshift mutations, 2 splice junction alterations, and 1 regulatory mutation. Of which, 5 novel mutations were identified in our present study: 2 frameshift mutations (p.Arg138GlyfsTer27, p.Leu511Profs*272); 2 missense mutations (p.Ala176Val, p.Phe268Leu), and 1 splice junction alteration (c.297+5G>A). Compound heterozygous mutations accounted for 80.6% of all variants. No mutational “hot-spot” was found. Most mutations of ALPL were located in exons 5, 7, 10, and 3. Notably, subjects that carrying single heterozygous mutations showed milder phenotypes of HPP, while subjects with nonsense mutations were associated with a severer phenotype. Conclusions HPP is a rare disease with often delayed diagnosis, and the incidence of HPP in China may be seriously underestimated. The present study expands the phenotypic and genotypic spectrum and the understanding of HPP in Chinese children. These findings will be useful for clinical assessment and shorten the diagnosis time for pediatric HPP in China.

scholarly journals Clinical Characteristics And Identification of Novel TGF-β1 Mutation In Three Unrelated Chinese Families With Progressive Diaphyseal Dysplasia

2021 ◽  
Author(s):  
Xiao-Hui Tao ◽  
Xing-Guang Yang ◽  
Zi-Yuan Wang ◽  
Yang Xu ◽  
Zhen-Lin Zhang ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Clinical Characteristics ◽  
Novel Mutation ◽  
The Novel ◽  
Chinese Families ◽  
Progressive Diaphyseal Dysplasia ◽  
Exon 4 ◽  
Diaphyseal Dysplasia ◽  
Tgf Β1

Abstract BackgroundTo investigate the clinical characteristics and molecular diagnosis of progressive diaphyseal dysplasia (PDD) in three unrelated Chinese families. MethodsThe present study recruited six patients aged 14 to 45 from three unrelated families with PDD, including five females and one male. Clinical manifestations, biochemical tests, radiographic examinations were analyzed and the TGF-β1 gene mutation was further identified by Sanger sequencing. In addition, data of treatment and follow-up were also collected.ResultsThe onset age of the patients ranged from 1 to 6 years. All the affected patients had family histories and were consisted with autosomal dominant inheritance pattern. All of them exhibited gait disturbance, fatigue, progressive bone pain, as well as muscle atrophy and weakness in limbs. Notably, there was one 15-year-old girl who experienced heart valve defects and tachycardia at birth. Laboratory examinations revealed the inflammatory markers were in high level, besides the extremely increased bone metabolism indicators. The thickened diaphysis of long bones and the narrowed medullary cavity were observed by radiography. Furthermore, radionuclide bone scan detected abnormal symmetrical radioactive concentration in the affected regions of bone. Sanger sequencing identified a missense heterozygous mutation in exon 4 of TGF-β1 gene, resulting in R218C, which confirmed PDD eventually. More important, a novel mutation c.669C>G in exon 4 of TGF-β1 gene harboring C223W were detected in family 3. Subsequent bioinformatics software predicted that the novel mutation was pathogenic. Our study also showed that zoledronic acid was not effective in the control of bone turnover markers and the relief of bone pain in patients with PDD.ConclusionIn addition to the typical PDD manifestations, the new phenotypic characteristics such as tachycardia and heart valve defect were firstly reported in one female patient carried the novel mutation p.Cys223Trp in TGF-β1 gene. In addition, our study indicated that the increased bone metabolism indicators and inflammatory markers may possess auxiliary diagnosis for PDD. More importantly, zoledronic acid was used to treat PDD patients in this study. After one-year follow-up, it was proved that the drug effect was not satisfactory, and new drugs need to be developed to treat the disease.

scholarly journals Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Lijun Xu ◽  
Qianqian Pang ◽  
Yan Jiang ◽  
Ou Wang ◽  
Mei Li ◽  
...  
Keyword(s):  
Serum Alkaline Phosphatase ◽  
Gene Mutations ◽  
Dominant Negative ◽  
Chinese Patients ◽  
Dominant Negative Effect ◽  
Healthy Controls ◽  
Missense Mutations ◽  
Genetic Characteristics ◽  
Chinese Families ◽  
Negative Effect

Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone and/or dental mineralization, and decreased serum alkaline phosphatase (ALP) activity. ALPL, the only gene related with HPP, encodes tissue non-specific ALP (TNSALP). Few studies were carried out in ALPL gene mutations in the Chinese population with HPP. The purpose of the present study is to elucidate the clinical and genetic characteristics of HPP in five unrelated Chinese families and two sporadic patients. Ten clinically diagnosed HPP patients from five unrelated Chinese families and two sporadic patients and fifty healthy controls were genetically investigated. All 12 exons and exon–intron boundaries of the ALPL gene were amplified by PCR and directly sequenced. The laboratory and radiological investigations were conducted simultaneously in these HPP ten patients. A 3D model of the TNSALP was used to predict the dominant negative effect of identified missense mutations. Three odonto, three childhood, and four adult types of HPP were clinically diagnosed. Ten mutations were identified in five unrelated Chinese families and two sporadic patients, including eight missense mutations and two frameshift mutations. Of which, four were novel: one frameshift mutation (p.R138Pfsx45); three missense mutations (p.C201R, p.V459A, p.C497S). No identical mutations and any other new ALPL mutations were found in unrelated 50 healthy controls. Our study demonstrated that the ALPL gene mutations are responsible for HPP in these Chinese families. These findings will be useful for clinicians to improve understanding of this heritable bone disorder.

scholarly journals Factors Affecting Phenotype Variability in a Family with CMT2B: Gender and LRSAM1 Genotype

2016 ◽  
Vol 8 (2) ◽  
pp. 120-126 ◽  
Author(s):  
Leema Reddy Peddareddygari ◽  
Kinsi Oberoi ◽  
Jaasrini Reddy Vellore ◽  
Raji P. Grewal
Keyword(s):  
Age Of Onset ◽  
Novel Mutation ◽  
Phenotypic Variability ◽  
Axonal Neuropathy ◽  
Missense Mutations ◽  
Factors Affecting ◽  
Charcot Marie Tooth Disease ◽  
Marked Variability ◽  
Phenotype Analysis ◽  
Family Gene

Charcot-Marie-Tooth disease type 2 (CMT2) is an autosomal dominant axonal neuropathy caused by mutations in various genes. The subtype CMT2B results from missense mutations in RAB7A, member RAS oncogene family gene, whereas missense mutations in the Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) gene cause CMT2P. We describe the genotype/phenotype analysis of a family in which a previously described mutation in the RAB7A gene and a novel mutation in the LRSAM1 gene were identified. In this family, none of the individuals had ulceromutilating features, and there was a marked variability in the age of onset. We discuss the possible etiology of the observed phenotypic variability including the role of gender and possible RAB7A/LRSAM1 gene interactions.

scholarly journals Clinical and Genetic Characteristics of Hypophosphatasia in Chinese Children

2020 ◽  
Author(s):  
Meijuan Liu ◽  
Min Liu ◽  
Xuejun Liang ◽  
Di Wu ◽  
Wenjing Li ◽  
...  
Keyword(s):  
Serum Alkaline Phosphatase ◽  
Hot Spot ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Splice Junction ◽  
Chinese Children ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Genetic Characteristics ◽  
Female Ratio

Abstract Background: Hypophosphatasia (HPP) is a rare inherited disorder, which is caused by loss-of-function mutations in the ALPL gene. HPP is a heterogeneous disease that has a wide spectrum of phenotypes. Few studies were carried out in the Chinese population with HPP, especially in children. Methods: The clinical and genetic characteristics of 10 Chinese children with HPP who were referred to the Beijing Children’s Hospital were described. We also reviewed previously reported HPP cases of children in China.Results: A total of 33 cases were identified, which included 2 perinatal lethal, 10 infantile, 10 childhood, and 11 odonto types of HPP. The male to female ratio was 24:9. The average age at onset was 0.69 years (ranged from 2 hours after birth to 14 years), while the average age at clinical diagnosis was 3.87 years (ranged from 2 hours after birth to 19 years). Serum alkaline phosphatase (ALP) levels were significantly decreased in patients with severe forms of HPP (perinatal lethal/infantile HPP) when compared with those with the mild forms of HPP (childhood/odonto HPP, P<0.01). Although serum phosphate levels were not significantly different (P>0.05), serum calcium levels were elevated, and serum intact parathyroid hormone (i-PTH) levels were decreased in patients with severe forms of HPP in comparison with those with the mild forms of HPP (P all <0.01). Genetic analyses identified 40 mutations in 31 HPP cases, including 28 missense mutations, 9 frameshift mutations, 2 splice junction alterations, and 1 regulatory mutation. Of which, 5 novel mutations were identified in our present study: 2 frameshift mutation (p.Arg138GlyfsTer27, p.Leu511Profs*272); 2 missense mutations (p.Ala176Val, p.Phe268Leu), and 1 splice junction alterations (c.297+5G>A). Compound heterozygous mutations accounted for 89.29% of all variants. No mutational “hot-spot” was found. Most mutations of ALPL were located in exons 5, 7, 10 and 3. Notably, subjects that carrying single heterozygous mutations showed milder phenotypes of HPP, while subjects with nonsense mutations were associated with a severe phenotype.Conclusions: HPP is a rare disease with often delayed diagnosis, and the incidence of HPP in China may be seriously underestimated. The present study expands the phenotypic and genotypic spectrum and our understanding of HPP in Chinese children.These findings will be useful for clinical assessment and shorten the diagnostics of pediatric HPP in China.

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