Primary Hypertrophic Osteoarthropathy Research Articles

Clinical and genetic characteristics of Chinese patients diagnosed with chronic enteropathy associated with SLCO2A1 gene

Background and aimsChronic enteropathy associated with SLCO2A1 gene is a rare intestinal disease caused by loss-of-function SLCO2A1 mutations, with clinical and genetic characteristics remaining largely unknown, especially in Chinese patients. This study aims to reveal clinical and genetic features of Chinese CEAS patients, highlighting the previously unreported or unemphasized characteristics.MethodsWe enrolled 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene admitted to Peking Union Medical College Hospital from January 2018 to December 2022. Clinical and genetic data of these patients were collected and analyzed.Results58.3% of patients were male, who also had primary hypertrophic osteoarthropathy, whereas female patients did not have primary hypertrophic osteoarthropathy. Apart from common symptoms associated with anemia and hypoalbuminemia, abdominal pain, ileus, diarrhea, and hematochezia were present. 4 of the 5 female patients had early-onset amenorrhea, though the causal relationship remained to be clarified. Endoscopy and computed tomography enterography revealed that lesions can occur in any part of the digestive tract, most commonly in the ileum. Pathology showed multiple superficial ulcers with adjacent vascular dilatation, and loss of SLCO2A1 expression, particularly in gastrointestinal vascular endothelial cells. Genetic analysis confirmed SLCO2A1 mutations in all patients and identified 11 new SLCO2A1 variants for CEAS.ConclusionsThis study reports new clinical, pathological, and genetic findings in 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene. This study provides insights into the pathogenesis of this disease. However, studies with larger sample sizes and more in-depth mechanism research are still required.

HYPERTROPHIC OSTEOARTHROPATHY IN A PATIENT WITH HETEROZYGOUS MUTATION IN THE SLCO2A1 GENE: A CASE REPORT

Hypertrophic osteoarthropathy (HOA) is a condition characterized by aberrant skin and osseous tissue proliferation in the distal extremities. Mutations in the 15-hydroxyprostaglandin dehydrogenase gene (HPGD) and the soluble carrier organic anion carrier family member 2A1 gene (SLCO2A1) were associated with primary HOA. Secondary HOA, which is also called as 'hypertrophic pulmonary osteoarthropathy' is responsible for 95-97% of cases. Herein, we present a 19-year-old female patient with primary HOA and heterozygous mutation in the SLCO2A1 gene.

Atypical primary hypertrophic osteoarthropathy diagnosed with a novel SLCO2A1 gene mutation

AbstractPrimary hypertrophic osteoarthropathy (HOA) is a rare condition with no identifiable cause, accounting for 3%–5% of all HOA cases. It is challenging to identify incomplete primary HOA, which can be misdiagnosed as other hypertrophic periostitis diseases. At least two of the four criteria set by Borochowitz and Rimoin (1990) must be present to diagnose primary HOA. Diagnostic difficulties due to incomplete or atypical manifestations are common. We present a case of incomplete primary PHOA at Hanoi Medical University Hospital in Vietnam. A 37-year-old male presented with ankle joint pain for nearly four years. X-ray and magnetic resonance imaging showed periostitis in the tibias and fibulas, which could not exclude Camurati–Engelmann disease. Finally, gene sequencing on the Illumina MiSeq system identified a missense mutation (c.295C>T) in the solute carrier organic anion transporter family member 2A1 (SLCO2A1) gene on chromosome 3. Our case report and literature review aim to improve specialists' understanding of incomplete primary HOA and reduce the frequency of missed diagnoses.

Features of the clinical course of pachydermoperiostosis with a verified mutation in the European type gene

Pachydermoperiostosis (primary hypertrophic osteoarthropathy) is an orphan disease, the main clinical manifestations of which include pin-shaped deformity of the fingers according to the type of «drumsticks», periostosis (non-inflammatory changes of the periosteum) of tubular bones, pachydermia of the face (hypertrophy and hyperplasia of all skin layers). Two genes associated with the development of pachydermoperiostosis are known — HPGD and SLCO2A1. Mutations in these genes lead to impaired prostaglandin E2 metabolism. This article describes a clinical case of a patient with pachydermoperiostosis, in which two mutations in the HPGD gene were detected during a molecular genetic study: in 1 exon (chr4-174522451-T-A, NM_000860.6:c.1A>T) and in 2 exon (chr4-174521985-AG-, NM_000860.6:c.175_176del) in compound-heterozygous state, while the c.1A>T mutation was previously described once, and the revealed biallelic combination of mutations in the HPGD gene was not previously found in the literature. This clinical case of pachydermoperiostosis is the second described in the Russian population, and the first with confirmed mutations in the HPGD gene. The article expands the knowledge about the correlation of genotype and phenotype in pachydermoperiostosis, which contributes to a faster and more correct interpretation of genetic information during genetic counseling.

Primary hypertrophic osteoarthropathy: genetics, clinical features and management.

Primary hypertrophic osteoarthropathy (PHO) is a genetic disorder mainly characterized by clubbing fingers, pachydermia and periostosis. Mutations in the HPGD or SLCO2A1 gene lead to impaired prostaglandin E2 (PGE2) degradation, thus elevating PGE2 levels. The identification of the causative genes has provided a better understanding of the underlying mechanisms. PHO can be divided into three subtypes according to its pathogenic gene and inheritance patterns. The onset age, sex ratio and clinical features differ among subtypes. The synthesis and signaling pathways of PGE2 are outlined in this review. Cyclooxygenase-2 (COX-2) is the key enzyme that acts as the rate-limiting step for prostaglandin production, thus COX-2 inhibitors have been used to treat this disease. Although this treatment showed effective results, it has side effects that restrain its use. Here, we reviewed the genetics, clinical features, differential diagnosis and current treatment options of PHO according to our many years of clinical research on the disease. We also discussed probable treatment that may be an option in the future.

Clinical and genetic characteristics of primary hypertrophic osteoarthropathy

Background. Primary hypertrophic osteoarthropathy is a rare genetically heterogeneous disease with three clinical variants. The classic one is a combination of hyperostosis, arthropathy and pachyderma and two variants with damage to only bone structures or pachyderma. Two genes responsible for the occurrence of primary hypertrophic osteoarthropathy have been identified: HPGD (debut age up to one year) and SLCO2A1 (debut in puberty and adolescence), whose products are involved in prostaglandin E2 metabolism. Two recurrent variants were identified in the HPGD gene: c.175_176delCT(p.Leu59fs) in patients from Europe and c.310_311delCT in patients from China. There were no clinical and genetic correlations in patients with different variants in the identified genes, which may be due to a small number of observations. The analysis of clinical manifestations in patients with newly identified variants or previously unidentified combinations of variants in a compound‑heterozygous state helps to understand the pathogenesis and prognosis of the course of the disease.Aim. To present the clinical and genetic characteristics of two Russian patients with primary hypertrophic osteoarthropathy caused by a newly identified combination of nucleotide variants in a compound‑heterozygous state in the HPGD and SLCO2A1 genes.Materials and methods. Clinical examination, radiography of the skeleton and chest, electrocardiography, echocardiography. Confirmation of the pathogenicity of the identified variants and clarification of the type of disease was carried out using automatic Sanger sequencing.Results. The clinical and genetic characteristics of two unrelated patients with primary hypertrophic osteoarthropathy caused by an undescribed combination of variants in the compound heterozygous state in the HPGD and SLCO2A1 genes were analyzed. In a patient with variants in the SLCO2A1 gene, the disease debuts at the age of 14 with deformities of the fingers, nails on the hands and feet, followed by the addition of burning pain in the distal parts of the arms and legs. At the age of 33, the examination revealed deformity of the fingers of the hands and feet by the type of drumsticks and nails by the type of watch glasses, enlargement of the knee joints, pronounced arthralgia. There were no signs of pachyderma. The new generation sequencing revealed two variants in the SLCO2A1 gene c.764G>A(p.Gly255Glu) in exon 6 and c.1333C>T(p.Arg445Cys) in exon 10. These variants were identified earlier in a compound‑heterozygous combination with other variants in patients with the classical phenotype of the disease, which were not present in the patient we observed. A feature of the case was pronounced hyperhidrosis and burning pain in the extremities, which may be due to stimulation of nociceptors in the musculoskeletal structures.Deformities of the fingers, nails of the hands and feet occurred in a patient with variants in the HPGD gene at 6 months. At the age of 9 years, a change in shape, stiffness and arthralgia of the knee and elbow joints without pachyderma were revealed. The identified variant with c.175_176delCT(p.Leu59fs) in this gene is often found in patients from European countries, and the other is c.1A>G(p.Met1?) discovered for the first time.Conclusion. The results allow us to conclude that when we found combinations of two variants in the HPGD and SLCO2A1 genes, there will be no pachyderma in the spectrum of clinical manifestations of primary hypertrophic osteoarthropathy. Sequencing of the new generation exome is the optimal diagnostic method.

Idiopathic hypertrophic osteoarthropathy misdiagnosed as juvenile idiopathic arthritis. Case study

Background. Pachydermoperiostosis (or primary hypertrophic osteoarthropathy) is a rare genetic disease that usually begins in childhood or adolescence, is characterized by certain clinical signs (pachydermia, periostosis, drum sticks) that gradually progress over many years until the disease stabilizes. Currently, there are 2 genes in which mutations are associated with the development of pachydermoperiostosis - HPGD and SLCO2A1. The functions of these genes are not fully understood, but their influence on the metabolism of prostaglandin E2 is known. Case presentation. We present a case of a 20-year-old patient mistakenly diagnosed as juvenile idiopathic arthritis. Symptoms on admission to the hospital: pain accompanied by swelling in the hands and feet, arthralgias in the talocrural joints, knees with slight swelling, paresthesia in the extremities, hyperhidrosis, fatigue. Clinical and paraclinical examinations confirmed the diagnosis of pachydermoperiostosis. Conclusions. Pachydermoperiostosis should be considered as a differential diagnosis when a patient presents with hypertrophic osteoarthropathy and acromegalic features.

Comparison of bone microstructure and strength in the distal radius and tibia between the different types of primary hypertrophic osteoarthropathy: an HR-pQCT study

SummaryPrimary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease that is grouped into PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2) due to different causative genes. Data comparing bone microstructure between the two subtypes are scarce. This is the first study to find that PHOAR1 patients had inferior bone microstructure compared with PHOAR2 patients.PurposeThe primary goal of this study was to assess bone microarchitecture and strength in PHOAR1 and PHOAR2 patients and to compare them with age- and sex-matched healthy controls (HCs). The secondary goal was to assess the differences between PHOAR1 and PHOAR2 patients.MethodsTwenty-seven male Chinese PHO patients (PHOAR1 = 7; PHOAR2 = 20) were recruited from Peking Union Medical College Hospital. The areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). Peripheral bone microarchitecture at the distal radius and tibia were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Biochemical markers of PGE2, bone turnover, and Dickkopf-1 (DKK1) were investigated.ResultsCompared with HCs, PHOAR1 and PHOAR2 patients had distinctively larger bone geometry, substantially lower vBMD at the radius and tibia, and compromised cortical microstructure at the radius. For trabecular bone, PHOAR1 and PHOAR2 patients showed different changes at the tibia. PHOAR1 patients had significant deficits in the trabecular compartment, resulting in lower estimated bone strength. Conversely, PHOAR2 patients showed a higher trabecular number, narrower trabecular separation, and lower trabecular network inhomogeneity than HCs, translating into preserved or slightly high estimated bone strength.ConclusionPHOAR1 patients had inferior bone microstructure and strength compared with PHOAR2 patients and HCs. Additionally, this study was the first to find differences in the bone microstructure between PHOAR1 and PHOAR2 patients.

Case report: Novel homozygous HPGD variant leads to primary hypertrophic osteoarthropathy with intussusception and acro-osteolysis in a Chinese family.

To perform molecular genetic analysis of a patient diagnosed with primary hypertrophic osteoarthropathy (PHO) with malnourishment, intussusception, and acro-osteolysis. At the age of 7 years, a boy born to a consanguineous couple was diagnosed with PHO attributed to delayed closure of the cranial suture, eczema, clubbing of fingers, and swelling of the knee and ankle. Clinical characteristics and follow-up data for 3 years were collected and analyzed. Trio whole-exome sequencing (WES) and copy number variant sequencing were used to screen for causative genetic variants. Candidate variants of the patient and his parents were confirmed by Sanger sequencing. When he was 7 years old, trio WES found that he had biallelic novel variants c.498 + 1G > A, inherited from his parents, in the HPGD gene. The patient was markedly malnourished. Ultrasonography and computed tomography showed intussusception with a gradual expansion of the duodenum, localized intestinal wall thickening, and acro-osteolysis. Cross-sectional blood tests showed that the patient had continuously decreased levels of serum 25-hydroxy vitamin D and serum ferritin at the age of 7and 10 years. PHO due to HPGD defects is rare in pediatric patients, and finding homozygous novel c.498 + 1G > A has expanded the spectrum of causative variants of HPGD and provided a clue for genotype-phenotype correlation analysis. Similar to mouse model results, human HPGD deficiency may also cause abnormal digestive tract development, and related secondary vitamin D deficiency and acro-osteolysis should be considered in HPGD-related PHO.

Pachydermoperiostosis Mimicking Inflammatory Arthritis: Case Description and Narrative Review

Pachydermoperiostosis (PDP), also called primary hypertrophic osteoarthropathy (HOA), is a rare genetic disease with typical thickening of the skin (pachydermia) and rheumatic manifestations, with clubbing of the fingers and toes and periostosis of the long bones visible on X-rays, as well as arthritis in large joints sometimes. Case: We describe a 23-year-old man with a complete form of PDP who presented with polyarthritis of the ankles and knees, with clubbing of the fingers and toes. He was treated with a non-steroidal anti-inflammatory drug (NSAID), etoricoxib, and with bisphosphonates (initially pamidronic acid i.v. and later oral risedronate 35 mg weekly). His joint pains and swelling disappeared, so that he could resume his daily activities. After eight years, the periostosis on the X-rays had disappeared. Discussion: The case is discussed, the literature regarding PDP is summarized and the differential diagnosis and treatment options are reviewed. Conclusions: PDP may present as polyarthritis. Clinicians should be aware of this diagnosis, as treatment is available and may improve the outcome of the patient. It is important to rule out secondary HOA due to pulmonary or cardiac disease, gastrointestinal malignancies and liver cirrhosis, especially when the dermatological findings are not typical. Further, acromegaly, thyroid acropachy and rheumatologic diseases should be excluded.

Novel pathogenic variants in SLCO2A1 causing autosomal dominant primary hypertrophic osteoarthropathy

Primary hypertrophic osteoarthropathy (PHO), or pachydermoperiostosis, is characterized by a clinical association including digital clubbing, periostosis and pachydermia. SLCO2A1 and HPGD genes are both responsible for PHO. The pathology is classically defined as an autosomal recessive disorder with clinical variability ranging from a mild to more severe phenotype. However, the hypothesis for an autosomal dominant form suggested for a long time was only demonstrated for the first time in 2021 for SLCO2A1. We aimed to detect a second pathogenic variant by a deep sequencing of the entire SLCO2A1 and HPGD genes, associated with functional transcription analysis in PHO patients harboring only one heterozygous variant. Among 10 PHO patients, 4 presented a single pathogenic or probably pathogenic novel variant in SLCO2A1 in heterozygous status (NM_005630.3: c.234+1G > A, c.1523_1524delCT, c.1625G > A and c.31delC), and the others carried homozygous pathogenic variants. For heterozygous forms, we found no additional pathogenic variant in HPGD or SLCO2A1. PHO can be a dominant form with age at disease onset later than that for the recessive form. This dominant form is not exceptional in young adults. In conclusion, both modes of inheritance of PHO explain the clinical variability and the difference in age at disease onset. Molecular analysis is especially required in the incomplete form to distinguish it from secondary hypertrophic osteoarthropathy.

A RARE CASE OF PRIMARY HYPERTROPHIC OSTEOARTHROPATHY : CASE REPORT

BACKGROUND: Hypertrophic osteoarthropathy (HOA) is characterized by abnormal growth of skin and osseous tissue at distal parts of the extremities, also known as orphan syndrome and Pierre Marrie-Bamberger syndrome. The peculiar bulbus deformity of the digital tips known as 2 “clubbing”, periosteal proliferation of long bones and painful effusion of synovium. HOA can be primary(idiopathic) and secondary. Although HOA is rare, secondary HOA is more common in certain diseases like chronic pulmonary disease, congenital heart disease, gastrointestinal disease, 5 and malignancies which may improve with treatment of the underlying disease. On the other hand primary HOA is idiopathic and its pathophysiology remains unclear. When idiopathic HOA is associated with pachyderma (thickened skin) is known as pachydermoperiostosis. In 4 extremely rare instance idiopathic HOA may occur without pachyderma. CLINICAL DESCRIPTION: We report a case of 4 years old female child came with complaints of pain and swelling in bilateral knee and ankle joints since 2 years, and developed pain and swelling in elbow and wrist joint since 1 year. On general examination she has grade 4 clubbing in ngers and toes. Suspecting HOA, relevant investigations sent to rule out secondary causes of HOA. After ruling out all causes of secondary HOA, we arrive at diagnosis of primary (idiopathic) HOA. MANAGEMENT: As there is no denitive management for primary HOA, we managed our patient symptomatically with painkillers. CONCLUSION: Reporting a rare case of primary HOA without pachyderma treated symptomatically with NSAIDS.

A rare helicobacter pylori infection-negative early gastric cancer in a young man with primary hypertrophic osteoarthropathy.

A rare helicobacter pylori infection-negative early gastric cancer in a young man with primary hypertrophic osteoarthropathy.

Primary hypertrophic osteoarthropathy – a rare cause of pain and arthritis in children. Description of 5 cases

Primary hypertrophic osteoarthropathy (PHOA) is a very rare disease. The typical triad of symptoms, i.e. digital clubbing, periosteal bone formation with bone and joint deformities and skin hypertrophy, may be accompanied by other specific conditions. In the majority of patients, the picture of the disease is incomplete. The dominant clinical symptom may be osteoarticular complaints. Moreover, the final confirmation of the diagnosis of the primary form of hypertrophic osteoarthropathy requires the analysis of much more frequent secondary causes of the disease. Diagnosing primary osteoarthropathy in children is particularly difficult. Some children report joint pain before the onset of the other symptoms of osteoarthropathy, while the physical and imaging examinations show features of arthritis. This can lead to misdiagnoses including the diagnosis of juvenile idiopathic arthritis (JIA) and the unnecessary use of immunosuppressive treatment. The present description of five patients from the Paediatric Rheumatology Department indicates diagnostic difficulties in children with PHOA. All of them were examined due to pain and features of arthritis. We observed an incomplete clinical picture of the disease. One patient required a revision of the previous diagnosis of JIA and discontinuation of ineffective treatment with disease-modifying antirheumatic drugs (DMARDs). PHOA should always be considered in the differential diagnosis of arthritis in children, due to the slow and often atypical development of symptoms, including the presence of pain and arthritis as the predominant symptom of the disease.

Clinical and biochemical characteristics of 12 Chinese primary hypertrophic osteoarthropathy patients with HPGD mutations.

Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disease mainly affecting the skeletal and skin. Two genes involved in prostaglandin degradation are known to be responsible for PHO: HPGD and SLCO2A1. HPGD gene mutation can cause PHO autosomal recessive 1 (PHOAR1). The purpose of the present study is to analyze the clinical and biochemical characteristics and HPGD gene mutations of 12 Chinese PHOAR1 patients. Twelve PHOAR1 patients from eleven families, including eleven males and one female, were enrolled in this study. Digital clubbing and periostosis came out to be the most common features, which always occur in the early childhood. We performed HPGD gene analysis and identified six novel (c.1A>G, c.34G>T, c.317T>A, c.475G>T, c.548C>T and c.421+1G>T) and one known (c.310_311delCT) HPGD mutations. The recurrent mutation c.310_311delCT were found in all eleven patients, suggesting it is a hotspot mutation. PHOAR1 patients are considered to have an autosomal recessive inheritance pattern. Here, in addition to nine compound heterozygous patients and two homozygous patients, we found one heterozygous patient and reviewed two heterozygous patients reported in other studies. In terms of biochemical characteristics, our PHOAR1 patients have elevated urinary prostaglandin E2 (PGE2) levels (P<0.001) and decreased urinary prostaglandin E metabolite (PGE-M) levels (P=0.04) compared with healthy controls. The patients' PGE2/PGE-M (E/M) ratio came out to be lower than normal subjects (P<0.001). This study provides a comprehensive description of the clinical phenotypes of Chinese PHOAR1 patients and expands the genotypic spectrum of the disease.

Pachydermoperiostosis (PDP): A Case Report

Abstract Pachydermoperiostosis (PDP) is the primary form of hypertrophic osteoarthropathy which accounts for 5% of all cases of the disorder. It is a rare hereditary disorder that is associated with digital clubbing, polyarthritis, cutis verticis gyrata, Seborrhea, eyelid ptosis, and hyperhidrosis. In this case report, we discussed a case of an incomplete form of primary hypertrophic osteoarthropathy characterised by evidence of bone abnormalities without pachydermia. Keywords: Pachydermoperiostosis, hypertrophic osteoarthropathy, periostosis.

Establishment of a novel human iPSC line (SDQLCHi032-A) derived from a patient with primary hypertrophic osteoarthropathy caused by HPGD homozygous mutation.

Primary hypertrophic osteoarthropathy, autosomal recessive type 1 (PHOAR1, MIM259100) is caused by mutations in the 15-hydroxyprostaglandin dehydrogenase gene (HPGD, MIM601688) on chromosome 4q34. An induced pluripotent stem cells (iPSCs) line was generated in our lab from peripheral blood mononuclear cells (PBMCs) of a 2-year-7-month-old girl with PHOAR1 carrying a homozygous mutation of c.310_311del in HPGD. The expression of pluripotency markers, absence of episomal vectors, preservation of normal karyotype, the potential of trilineage differentiation in vitro, were confirmed in the obtained iPSCs line.

SLCO2A1 gene is the causal gene for both primary hypertrophic osteoarthropathy and hereditary chronic enteropathy.

SLCO2A1 gene is the causal gene for both primary hypertrophic osteoarthropathy and hereditary chronic enteropathy.

Clinical and genetic characteristics of patients with chronic enteropathy associated with SLCO2A1 gene

Objective: To determine the clinical features and genetic characters of patients with chronic enteropathy associated SLCO2A1 gene (CEAS). Methods: Five CEAS patients diagnosed at Peking Union Medical College Hospital from January 2012 to December 2019 were enrolled in this study. The clinical manifestations, laboratory test, radiological and endoscopic findings, gene detections, treatments and prognosis of these patients were reviewed and analyzed. Results: Five male patients presented gastrointestinal symptoms after puberty, including abdominal pain, diarrhea, intermittent melena or hematochezia, incomplete bowel obstruction, anemia, hypoalbuminemia and hypokalemia. The whole gastrointestinal tract except esophagus could be involved, especially the stomach and ileum. Intestinal lesions were characterized by multiple shallow ulcers with stenosis in the layers of mucosa and submucosa. Five patients were all accompanied with primary hypertrophic osteoarthropathy (PHO), and 1 with myelofibrosis and thoracic duct dysplasia. All patients were homozygous or compound heterozygous mutations of SLCO2A1 gene. Conventional treatment of inflammatory bowel disease and COX-2 inhibitors were ineffective. Conclusions: CEAS is an autosomal recessive genetic disease which widely involves the gastrointestinal tract, and can be associated with skin and bone involvement. There is no effective treatment for CEAS at present. CEAS is a different entity from other inflammatory gastrointestinal diseases.

Characterization of Mineral and Bone Metabolism Biomarkers in a Chinese Consanguineous Twin Family with Primary Hypertrophic Osteoarthropathy.

Purpose Primary hypertrophic osteoarthropathy (PHO) is a rare, autosomal, recessive genetic disease characterized by digital clubbing, periostosis, and pachydermia. The underlying cause for the pathogenesis of this disease is a defect in prostaglandin E2 (PGE2) degradation, caused by mutations in HPGD or SLCO2A1. In this study, we describe the clinical characteristics, SLCO2A1 mutations, and bone metabolic markers of a PHO pedigree from a Chinese consanguineous twin family. Methods Whole blood and urine samples were collected from all the family members. All the exons and exon-intron boundaries of the HPGD and SLCO2A1 genes were amplified using polymerase chain reaction (PCR) and sequenced. The biomarkers of mineral and bone metabolism, including calcium, phosphorus, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), bone Gla-protein (BGP), C-terminal telopeptide of type I collagen (β-CTX), and urinary calcium/creatinine ratio (Uca/Ucr) were detected. Results A homozygous (nonsense) mutation in the SLCO2A1 gene (c.1807C >T/p.R603∗) was detected in the proband. Five heterozygous carriers were also identified among his relatives, including his twin brother. The serum BGP (225.5 ng/ml), β-CTX (4112 pg/ml), and Uca/Ucr (0.63) levels were significantly elevated, while the 25(OH)D (37.1 nmol/L) level was reduced in the proband. The proband's twin brother displayed increased levels of β-CTX (901 pg/ml) and insufficiency of 25(OH)D (67.29 nmol/L), while the other heterozygous carriers only displayed 25(OH)D insufficiency. Conclusion The patients with PHO displayed an active state of bone reconstruction. There may be a lack of vitamin D, accompanied by an increase in BGP and β-CTX levels. Heterozygous mutations of SLCO2A1 might lead to mild PHO.