Pseudohypoparathyroidism: an endocrine orphan disease. case report

Introduction: Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterized by resistance to the parathyroid hormone. There are few reports on PHP in Colombia, so the publication of the present case contributes to increase the interest in its research in the clinical setting. Case presentation: An 18-year-old male with a history of hypothyroidism diagnosed at 4 months of age, stunted growth, delayed puberty, obesity, brachydactyly, pathologic fractures, femoral osteochondroma, insomnia, paresthesia, and chronic constipation was referred to the endocrinology service of a tertiary care center in Bogotá (Colombia) after being hospitalized following a seizure episode. On admission, laboratory tests revealed hypocalcemia, hyperphosphatemia, 25-hydroxy vitamin D in the range of insufficiency and elevated PTH. Imaging studies showed heterotopic ossifications and calcifications of the basal ganglia. A genetic study confirmed the diagnosis of PHP1A, so treatment was started with calcium, cholecalciferol and phosphorus chelators, leading to a satisfactory course. Both the patient and his first-degree relatives received genetic counseling and interdisciplinary assessment. Conclusion: Although PHP type 1A is an unrecognized complex genetic disorder, it has a critical clinical importance within the differential diagnoses of hypocalcemia. Without prompt diagnosis and treatment, patients may experience serious and potentially fatal metabolic consequences.

Introducción. El seudohipoparatiroidismo (SPT) es un trastorno genético poco frecuente que se caracteriza por la resistencia a la hormona paratiroidea (PTH). En Colombia existen pocos reportes sobre esta enfermedad, por lo que la publicación del presente caso contribuye a aumentar el interés en su búsqueda en el ámbito clínico. Presentación del caso. Hombre de 18 años con antecedente de hipotiroidismo (diagnosticado a los 4 meses de nacido), retraso del crecimiento, desarrollo puberal tardío, obesidad, braquidactilia, fracturas patológicas, osteocondroma femoral, insomnio, parestesias y estreñimiento crónico, quien asistió al servicio de endocrinología de un hospital de tercer nivel de Bogotá (Colombia) remitido luego de haber estado hospitalizado por un episodio convulsivo. En dicha hospitalización los laboratorios evidenciaron hipocalcemia, hiperfosfatemia y 25-OH vitamina D en rango de insuficiencia con niveles elevados de PTH, y los estudios imagenológicos demostraron osificaciones heterotópicas y calcificaciones de ganglios basales del cerebro. Al paciente se le realizó un estudio genético que confirmó el diagnóstico de SPT1A, por lo que se le inició manejo con suplencia de calcio, colecalciferol y quelantes de fósforo, con lo cual evolucionó satisfactoriamente. Tanto el paciente como sus familiares de primer grado recibieron asesoramiento y valoración interdisciplinaria. Conclusiones. El SPT1A es un trastorno genético complejo poco conocido pero de alta importancia clínica dentro de los diagnósticos diferenciales de hipocalcemia que debe considerarse ya que sin el diagnóstico y tratamiento oportunos, los pacientes pueden presentar consecuencias metabólicas graves y potencialmente fatales.

Deficiencia de vitamina D asociada a hiperfosfatemia en niños / Vitamin D deficiency associated with hyperphosphatemia in children

RESUMEN Los niños con deficiencia de vitamina D pueden tener fósforo normal o alto a pesar de tener una prueba de hormona paratiroidea (PTH) elevada. El pseudohipoparatiroidismo (PHP) se caracteriza por cursar con hiperfosfatemia. La similitud que puede ocurrir entre la deficiencia de vitamina D asociada a hiperfosfatemia y el PHP hace importante revisar reportes de casos de deficiencia de vitamina D asociada a hiperfosfatemia para entender por qué puede ocurrir esta asociación y cuál es la relevancia de estudiar el nivel de vitamina D en niños con sospecha de PHP. El objetivo de esta revisión fue identificar reportes de niños con deficiencia de vitamina D asociada a hiperfosfatemia y discutir los mecanismos de esta asociación. Se identificaron reportes de 7 casos en niños. La deficiencia de vitamina D reduciría la respuesta fosfatúrica ante una PTH elevada. Se concluye que es importante descartar deficiencia de vitamina D en todo niño con sospecha de PHP.

ABSTRACT Children with vitamin D deficiency can have normal or high phosphorus despite having a high parathyroid hormone test (PTH). Pseudohypoparathyroidism (PHP) is characterized by hyperphosphatemia. The similarity that can occur between vitamin D deficiency associated with hyperphosphatemia and PHP makes it important to review case reports of vitamin D deficiency associated with hyperphosphatemia to understand why this association may occur and what is the relevance of studying the vitamin D level in children with suspected PHP. The aim of this review was to identify reports of children with vitamin D deficiency associated with hyperphosphatemia and to discuss the mechanisms of this association. Reports of 7 children cases were identified. Vitamin D deficiency could reduce the phosphaturic response to elevated PTH. It is concluded that it is important to rule out vitamin D deficiency in all children with suspected PHP.

Clinical characteristics and genetic analysis of two cases of pseudohypoparathyroidism type Ⅰa with early-onset skin nodules as the diagnostic clue / 中华皮肤科杂志

Clinical features of and genetic mutations in two cases of pseudohypoparathyroidism type Ⅰ a(PHP Ⅰ a) with early-onset skin nodules were analyzed.Both of the two patients were males,and their ages at onset were 2 and 3 months respectively.They both presented with early-onset skin nodules as the main clinical manifestation,and were clinically characterized by a round face,short neck and early obesity.Histopathological examination of skin lesions showed subcutaneous ectopic osteogenesis in both patients.The first patient had low blood calcium,high blood phosphorus,high parathyroid hormone (PTH),and gene sequencing showed a heterozygous mutation c.399delT causing a T base deletion at position 399 in exon 5 of the GNAS gene.The second patient had normal blood calcium and phosphorus levels as well as normal PTH levels at early stage,and gene sequencing showed a heterozygous mutation c.939delT causing a T base deletion at position 939 in exon 9 of the GNAS gene.The blood PTH level was found to increase in the second patient after 1-year follow-up.Both the patients were confirmedly diagnosed with PHP Ⅰa.After treatment with vitamin D3,no new skin nodules occurred,and the blood calcium and phosphorus levels returned to normal.

Management of pseudohypoparathyroidism in pregnancy: a rare entity

Pseudohypoparathyroidism is a very rare genetic disorder and during pregnancy poses multiple challenges related to its monitoring and management. Authors present the case of a  30year old primigravida who was a diagnosed case of pseudohypoparathyroidism since 22 yrs of age, presented to our obs/gynae OPD at 5+5 wks of POG. She was managed by serial monitoring of serum calcium, phosphate and vitamin D throughout  pregnancy with careful dose modification of calcium from 1gm to 3.5gm daily and vitamin D from  0.5mcg  to 1.5mcg daily. During her course of pregnancy, she developed gestational hypothyroidism, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy and gestational hypertension which were controlled and managed successfully. She had an elective caesarean section at 37+6 wks POG for transverse lie. Both maternal and perinatal outcome were good. Patient was discharged with advice to continue with her monitoring of serum calcium, phosphate, vitamin D along with supplementation of calcium and vitamin D life long.

Seudohipoparatiroidismo 1b / Pseudohypoparathyroidism 1b

RESUMEN El seudohipoparatiroidismo 1b se caracteriza por resistencia aislada a la parathormona, en ausencia de las manifestaciones típicas de la osteodisfrofia hereditaria de Albright; debido a alteraciones epigenéticas del locus GNAS. Puede presentarse de forma esporádica, o heredado de manera autosómico dominante por vía materna. Se presenta paciente masculino de 31 años, con antecedentes de tumores óseos y calcificaciones cerebrales diagnosticados a los 14 años; que se consulta por presentar mareo intenso, rigidez del cuello y la boca, dificultad para hablar y tragar, desorientación y trastornos de percepción; con fenotipo y somatometría normales, y signos de tetania latente (Chvostek y Trouseau positivos). Los estudios realizados mostraron: hipocalcemia, hiperfosfatemia, aumento de niveles de parathormona y múltiples calcificaciones en cerebro y cerebelo. Con tales hallazgos se emite el diagnóstico de seudohipoparatiroidismo 1b, el cual se confirma mediante pruebas moleculares con alteración en el patrón de metilación en el locus GNAS. No presentó alteraciones en el estudio de secuenciación de los 13 exones codificantes del GNAS. Se concluyó como un caso esporádico ante la ausencia de historia familiar de hipocalcemia, combinado con amplia pérdida de metilación del gen GNAS y la no evidencia de deleciones. Se presenta el primer reporte de esta enfermedad en Cuba con estudio molecular(AU)

ABSTRACT Pseudohypoparathyroidism 1b is characterized by isolated resistance to parathormone, in the absence of the typical manifestations of hereditary Albright osteodysphrophy; due to epigenetic alterations of the GNAS locus. It can occur sporadically, or inherited in an autosomal dominant way through the mother. We report the case of a 31-year-old male patient, with history of bone tumors and cerebral calcifications diagnosed at age 14. She came to consultation due to severe dizziness, stiff neck and mouth, difficulty speaking and swallowing, disorientation and perception disorders; he showed normal phenotype and somatometry, and signs of latent tetany (positive Chvostek and Trouseau). Studies have shown hypocalcaemia, hyperphosphatemia, increased levels of parathormone and multiple calcifications in the brain and cerebellum. These findings, pseudohypoparathyroidism 1b is diagnosed confirmed by molecular tests showing alteration in the methylation pattern in the GNAS locus. There were no alterations in the sequencing study of the 13 exons coding for GNAS. It was concluded as a sporadic case in the absence of a family history of hypocalcemia, combined with extensive loss of GNAS gene methylation and no evidence of deletions. This is the first report this disease with molecular study in Cuba(AU)

Pseudohypoparathyroidism: A case of hypocalcemia and hypothyroidism diagnosed during the postpartum period

@#We describe a 29-year-old Para 1 post-Emergency Lower Segment Caesarean Section (EMLSCS) for fetal distress and Preterm Rupture of the Membrane (PROM) referred by the Obstetric team for persistent bradycardia. She had the typical features of Albright’s Hereditary Osteodystrophy (AHO). The laboratory investigation revealed hypocalcemia, hyperphosphatemia with a high Parathyroid hormone (PTH) level and low free Thyroxine 4 (fT4) with high Thyroid Stimulating Hormone (TSH). The patient was diagnosed with Pseudohypoparathyroidism (PHP) Type 1A associated with TSH resistance based on the somatic features of AHO present as well as biochemical and radiological abnormalities.

Clinical and gene methylation analysis of type 1b pseudohypoparathyroidism / 中华内分泌代谢杂志

Objective This study was carried out to analyze the clinical characteristics of pseudohypopara-thyroidism(PHP) type 1b, and to improve the understanding and diagnosis of the disease. Methods Five patients with molecular diagnosis of pseudohypoparathyroidism type 1b in our hospital during 2018 were enrolled, their clinical data, biochemical indicators, imaging, and gene detection results were analyzed. Results There were 4 females and 1 male, with low calcium, high phosphorus and high PTH seran con centrations. The onset age span was large and the onset symptoms were different. Family history may not be obvious. There wer was abnormal methylation of GNAS gene or deletion of exon STX16 in methylation-specific multiplex ligation-dependent probe amplification ( MS-MLPA ) detection while gene sequeming result was negative. Conclusion MS-MLPA detection was still needed in patients with suspected PHP but negative gene sequencing result. Different methylation abnormalities and copy number variations might be correlated with the onset symptoms and familial of type 1b PHP.

Neonatal transient pseudohypoparathyroidism: could it be included among inactivating parathyroid hormone (PTH)/PTH-related protein signalling disorders?

We report a case of transient pseudohypoparathyroidism in a full-term newborn that presented at 20 hours of life with hypocalcemic seizures, hyperphosphatemia and raised parathormone levels. The diagnosis of pseudohypoparathyroidism was made according to biochemical investigations. The infant was treated with calcium supplementation and vitamin D analog therapy, and he remained stable and symptom-free with normal serum biochemistries during follow-up. We suggest that transient pseudohypoparathyroidism of the newborn (ntPHP) might be included among inactivating parathyroid hormone (PTH)/PTH-related protein signaling disorders as defined by the classification schema recently proposed by the European Pseudohypoparathyroidism Network. To the best of our knowledge, this is the first report in which the new classification has been applied to a case of ntPHP.

Clinical and gene methylation analysis of type 1b pseudohypoparathyroidism / 中华内分泌代谢杂志

Objective@#This study was carried out to analyze the clinical characteristics of pseudohypopara-thyroidism(PHP) type 1b, and to improve the understanding and diagnosis of the disease.@*Methods@#Five patients with molecular diagnosis of pseudohypoparathyroidism type 1b in our hospital during 2018 were enrolled, their clinical data, biochemical indicators, imaging, and gene detection results were analyzed.@*Results@#There were 4 females and 1 male, with low calcium, high phosphorus and high PTH serum concentrations. The onset age span was large and the onset symptoms were different. Family history may not be obvious. There was abnormal methylation of GNAS gene or deletion of exon STX16 in methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) detection while gene sequencing result was negative.@*Conclusion@#MS-MLPA detection was still needed in patients with suspected PHP but negative gene sequencing result. Different methylation abnormalities and copy number variations might be correlated with the onset symptoms and familial of type 1b PHP.

Clinical analysis of 14 cases of pseudohypoparathyroidism in children / 国际儿科学杂志

Objective@#To analyze the clinical characteristics and treatment of pseudohypoparathyroidism(PHP) in children and to increase clinicians′understanding of this disorder.@*Methods@#From January 2008 to November 2018, a total of 14 PHP patients at our hospital were retrospectively analyzed, as regarding the clinical manifestation, laboratory examination and imaging data.The patients were further divided into two groups according to onset age: group A(under 1 year) and group B(over or equal to 1 year). The laboratory findings were compared between the two groups.@*Results@#Of the 14 patients(10 boys and 4 girls), the median age of onset was 12 years(range: 1 day to 16 years). Epilepsy is one of the most common manifestations of PHP.Laboratory findings include hypocalcemia(1.06-2.18mmol/L), hyperphosphatemia(2.1-3.5 mmol/L), and elevated concentrations of PTH(105.6-733.0 pg/ml). PTH levels were significantly lower in the group A than in group B(Z=2.07, P=0.042). Five patients were found to have calcifications in bilateral basal ganglia and cerebral parenchyma by head CT.All the patients were improved after treatment, which included calcium gluconate injection to control tetany, calcium supplement combined with vitamin D and/or calcitriol orally.@*Conclusion@#For children who presented frequent hypocalcemia tetany and calcifications in head CT, serum calcium, phosphorus, PTH levels should be further investigated to make a correct diagnosis.Calcium supplement combined with vitamin D or its metabolites is an effective therapy for PHP children.

Clinical analysis of 14 cases of pseudohypoparathyroidism in children / 国际儿科学杂志

Objective To analyze the clinical characteristics and treatment of pseudohypoparathyroidism (PHP) in children and to increase clinicians'understanding of this disorder.Methods From January 2008 to November 2018,a total of 14 PHP patients at our hospital were retrospectively analyzed,as regarding the clinical manifestation,laboratory examination and imaging data.The patients were further divided into two groups according to onset age:group A (under 1 year) and group B (over or equal to 1 year).The laboratory findings were compared between the two groups.Results Of the 14 patients (10 boys and 4 girls),the median age of onset was 12 years (range:1 day to 16 years).Epilepsy is one of the most common manifestations of PHP.Laboratory findings include hypocalcemia (1.06-2.18mmol/L),hyperphosphatemia (2.1-3.5 mmol/L),and elevated concentrations of PTH (105.6-733.0 pg/ml).PTH levels were significantly lower in the group A than in group B (Z =2.07,P =0.042).Five patients were found to have calcifications in bilateral basal ganglia and cerebral parenchyma by head CT.All the patients were improved after treatment,which included calcium gluconate injection to control tetany,calcium supplement combined with vitamin D and/or calcitriol orally.Conclusion For children who presented frequent hypocalcemia tetany and calcifications in head CT,serum calcium,phosphorus,PTH levels should be further investigated to make a correct diagnosis.Calcium supplement combined with vitamin D or its metabolites is an effective therapy for PHP children.

A preliminary study of the quality of life and muscle strength in patients with pseudohypoparathyroidism / 中华内分泌代谢杂志

Objective To explore the quality of life ( QoL ) and muscle strength in patients with pseudohypoparathyroidism ( PHP ) under regular treatment. Methods Twenty-three patients with PHP regularly followed at Peking Union Medical College Hospital from June 2017 to June 2018 were included. Age- and gender-matched 23 patients with nonsurgical hypoparathyroidism ( nHPT) and 23 healthy controls were also included. Short Form 36 Health Survey questionnaire version 2 ( SF36v2) were used to evaluate the QoL. Grip strength and repeated chair stand ( RCS) were used to assess muscle strength for upper and lower limbs respectively. Results Except for physical functioning, patients of PHP group had reduced scores in all other subdomains of SF36v2 compared to healthy controls ( P<0.05) . Comparing to nHPT patients, PHP patients had a higher score in social functioning, while no difference was found in other subdomains of SF36v2. Grip strength and RCS tests were similar in PHP patients and healthy controls. Conclusions Comparing to healthy controls, patients with PHP still had impaired QoL despite regular management, no significant difference of upper and lower limb muscle strength was found between PHP group and healthy controls.

Late diagnosis of pseudohypoparathyroidism in adulthood. Case series / Pseudohipoparatiroidismo diagnosticado tardíamente en la adultez, una serie de casos

Abstract Introduction: Pseudohypoparathyroidism (PHP) is a rare hereditary disease, characterized by hypocalcemia/hyperphosphatemia secondary to peripheral resistance to parathyroid hormone (PTH). PHP diagnosis is usually precluded since hypocalcemia is considered as the primary diagnosis, thus delaying further diagnostic studies and preventing an adequate management of this clinical condition. Materials and methods: Retrospective review of the databases of the Endocrinology departments of two tertiary care centers of Medellin, Colombia from January 2012 to December 2016. Patients diagnosed with PHP based on clinical presentation and confirmatory laboratory values were included. Results: Four patients met the inclusion criteria. All PHP cases were diagnosed in adulthood despite strong early clinical and laboratory evidence of the disease. Three patients were diagnosed with Fahr's syndrome and two with Albright's hereditary osteodystrophy. The mean values obtained were PTH of 376.8 pg/mL, calcium of 6.17 mg/dL and phosphorus of 6.55 mg/dL. Conclusions: PHP is a rare disorder. This paper describes four PHP cases diagnosed during adulthood. Emphasis should be placed on the judicious approach to the patient with hypocalcemia and hyperphosphatemia with increased PTH and normal renal function, since these symptoms strongly suggest a diagnosis of PHP.

Resumen Introducción. El pseudohipoparatiroidismo (PHP) es una condición rara caracterizada por hipocalcemia e hiperfosfatemia secundarias a resistencia periférica a la hormona paratiroidea (PTH). Es frecuente que la hipocalcemia sea establecida de forma equivocada como diagnóstico primario y que el diagnóstico definitivo de PHP sea tardío, difiriendo los estudios y el manejo específico que exigen estos pacientes. Materiales y métodos. Se revisaron de forma retrospectiva las bases de datos de endocrinología de dos centros terciarios de Medellín, Colombia, desde enero de 2012 a diciembre de 2016. Se incluyeron pacientes con diagnóstico de PHP por presentación clínica y valores confirmatorios de laboratorio. Resultados. Cuatro pacientes cumplieron los criterios de inclusión. Todos los casos fueron diagnosticados en la adultez a pesar de tener evidencia temprana, clínica y bioquímica de la enfermedad. Tres pacientes tenían síndrome de Fahr y dos tenían osteodistrofia hereditaria de Albright. Los valores medios registrados fueron PTH de 376.8 pg/mL, calcio de 6.17 mg/dL y fósforo de 6.55 mg/dL. Conclusiones. El PHP es un trastorno raro; se describen cuatro casos diagnosticados de forma tardía en la adultez. Se enfatiza en el enfoque juicioso del paciente con hipocalcemia, la cual, en presencia de hiperfosfatemia con PTH elevada y función renal normal, debe hacer sospechar el diagnóstico de PHP.

Pseudohipoparatiroidismo neonatal transitorio / Transient neonatal pseudohypoparathyroidism

Se presenta el caso de un neonato pretérmino de 36 semanas de edad gestacional, que nace vía cesárea por preeclamsia severa y macrosomía fetal, manejado en terapia intensiva neonatal por taquipnea transitoria complicada con hipertensión pulmonar, con soporte ventilatorio, sedación, relajación e inótropicos. Al sexto día de vida presenta convulsiones tónicas generalizadas que ceden con el uso de anticonvulsivantes, pero se detectan alteraciones electrolíticas severas (hipocalcemia, hipomagnesemia e hiperfosforemia). Se logra mejoría de los electrolitos pero al suspender las correcciones reaparecen los trastornos electrolíticos a pesar de mantener aportes adecuados de los mismos con niveles elevados de paratohormona (PTH), confirmando diagnóstico de pseudohipoparatiroidismo neonatal transitorio, secundario al uso de medicamentos.

We present the case of a preterm neonate of 36 weeks of gestational age, who was born via cesarean section due to severe preeclampsia and fetal macrosomy, managed in neonatal intensive therapy by transient tachypnea complicated with pulmonary hypertension, with ventilatory, sedation, relaxation and inotropic support, with. On the sixth day of life he presents generalized tonic seizures that subside with the use of anticonvulsants, but severe electrolyte alterations are detected (hypocalcemia, hypomagnesemia and hyperphosphoremia ). Electrolyte improvement is achieved but when corrections are stopped reappear electrolyte disorders despite maintaining adecuate contributions with high levels of paratohormone (PTH), confirming the diagnosis of transient neonatal pseudohypoparathyroidism, secondary to the use of medications.

Pseudohipoparatiroidismo de presentación tardía: reporte de dos casos / Pseudohypoparathyroidism: report of two cases of late presentation

Pseudohypoparathyroidism (PHP) is a group of rare genetic disorders that share organ targeted resistance to the action of parathyroid hormone (PTH) as a common feature. Biochemically, they may present with hypocalcemia, hyperphosphatemia and elevated PTH. Some forms present with a specific phenotype: short stature, round facies, short neck, obesity, brachydactyly and subcutaneous calcifications, called Albrigth's Hereditary Osteodystrophy (AHO). This spectrum of disorders are caused by several alterations in the gene coding for the alpha subunit of the G protein (GNAS): an ubiquitous signaling protein that mediates the action of numerous hormones such as PTH, TSH, gonadotropins, and ACTH, among others. According to their inheritance with maternal or paternal imprinting, they may manifest in a diversity of clinical forms. Although most commonly diagnosed during childhood, PHP may manifest clinically during adolescence or early adulthood. We report two late presenting cases of pseudohypoparathyroidism. A 21-year-old female with biochemical abnormalities characteristic of pseudohypoparathyroidism who was misdiagnosed as epilepsy and a 13-year-old boy with the classic AHO phenotype but without alterations in phospho-calcium metabolism, compatible with pseudopseudohypoparathyrodism.

Albright hereditary osteodystrophy: dental management case report / Osteodistrofia hereditária de albright: relato de caso de manejo odontológico

ABSTRACT Albright hereditary osteodystrophy is a disorder comprising phenotypic characteristics of genetic origin, such as short stature, obesity, and brachydactyly. It is a rare disorder and is related to pseudohypoparathyroidism. Within dentistry, it may be associated with enamel hypoplasia and late eruption. Furthermore, due to neurological problems, these patients may impose behavioural difficulties during dental appointments. The present study aims to describe the case of a patient with a possible diagnosis of Albright hereditary osteodystrophy, presenting symptoms and limitations to dental management.

RESUMO A Osteodistrofia Hereditária de Albrighth é uma alteração que compreende características fenotípicas de origem genética, tais como baixa estatura, obesidade e braquidactília. É uma desordem rara e está relacionada com o pseudo-hipoparatireoidismo. No âmbito da Odontologia pode estar associada à hipoplasia de esmalte e erupção tardia dos dentes. Além disto em função de problemas neurológicos estes pacientes podem impor dificuldades de comportamento no momento do atendimento. O presente estudo objetivou descrever um caso clínico de uma paciente, com o possível diagnóstico de Osteodistrofia Hereditária de Albright, apresentando sintomas e limitações ao tratamento odontológico.

Clinical analysis of 18 cases of pseudohypoparathyroidism / 中华内分泌代谢杂志

Objective To analyze the clinical characteristics of pseudohypoparathyroidism ( PHP ) inpatients in our hospital from January 2008 to December 2017 and to gain a better understanding of this disorder. Methods 18 inpatients diagnosed as sporadic PHP in our hospital were analyzed retrospectively, as regarding the clinical manifestation, laboratory examination and imaging data. Results 18 inpatients were diagnosed sporadic PHP consisting of 12 males and 6 females, with 13 adults and 5 child participants respectively. The medium age of onset was 14 (6-57), and the average age at diagnosis was (24.9± 14.7) years old. Initial onset of symptoms reported were: 12 patients complained of tetany, 3 reported convulsions, 1 reported numbness, 1 reported dysnoesia, and 1 were asymptomatic. Among them: 3 patients were found to have short distal phalanx, 7 displayed a round face, and 3 out of 15 adults were less than 155 cm in height. 12 patients had a positive Trousseau sign, 1 had an ectopic calcification. 11 were found to have intercranial massive calcifications by head computed tomography. Serum calcium was reported at (1.58 ± 0.11) mmol/ L and parathyroid hormone was (359.5 ± 146.6) pg/ ml. 3 patients were discovered to have hypothyroidism, 2 had been misdiagnosed with epilepsy, and 1 with encephalitis. Conclusions Tetany and intracranial calcifications were the most common signs of PHP patients. A number of the PHP cases in this study lacked typical Albright's Hereditary Osteodystrophy ( AHO) appearance. The age of onset and or duration of the disease varied somewhat in the different patient populations. The heterogeneity nature of the clinical manifestations of PHP makes it difficult to diagnose. It is therefore important to make accurate differential diagnosis of PHP to avoid misdiagnosis of the condition.

Analysis of clinical characteristics on a hybrid deletion mutation of GNAS-AS1 gene Exon 5E leading to pseudohypoparathyroidism with hypokalemia and hypomagnesemia / 中华内分泌代谢杂志

To improve clinicians'understanding of the diagnosis and treatment of pseudohypoparathyroidism with hypokalemia and hypomagnesemia. The clinical manifestations, laboratory examinations, imaging data, gene results, diagnosis and treatment of a pseudohypoparathyroidism type Ⅰb with hypokalemia and hypomagnesemia patient were retrospectively analyzed. The literatures related to pseudohypoparathyroidism in recent years were also summarized. A young man, mainly manifested as repeated tetany. The physical examination showed short stature, round face, short neck, with positive Trousseau sign. The laboratory examination revealed parathyroid hormone resistance, hypocalcemia, hyperphosphatemia, hypokalemia and hypomagnesemia. The urinary calcium and phosphorus levels were low. Cerebral magnetic resonance imaging ( MRI ) showed bilateral basal ganglia calcification. Genetic screening revealed a hybrid deletion mutation of GNAS-AS1 gene Exon 5E. After the supplement of element calcium 720 mg/d, plain vitamin D 375 U/d, active vitamin D 0.5 μg/d and potassium chloride 3 g/d, the levels of blood potassium and phosphorus rise to normal, the levels of blood calcium and magnesium were close to normal. Pseudohypoparathyroidism typeⅠb may accompany with hypokalemia and hypomagnesemia.

Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q: A case report

Pseudohypoparathyroidism type 1b (PHP 1b) is the result of end organ resistance to parathyroid hormone (PTH) in the absence of any features of Albright's hereditary osteodystrophy. There are two subtypes of PHP 1b with different genetic mechanisms. One subtype is related to a maternally derived 3kb microdeletion involving STX 16 gene, and is inherited in an autosomal dominant mode. Familial autosomal dominant inheritance of PHP 1b is relatively rare. The other subtype is associated with more extensive loss of imprinting at the GNAS locus that affects at least one additional differential methylated (hypermethylation at neuroendocrine secretory protein and hypomethylation at antisense transcript and or extra-large stimulatory G protein region) without microdeletion of the STX 16 or AS gene. It can be sporadic due to an imprinting defect in the GNAS gene. In our case, an 8-year-old girl was referred for suspected PHP with no feature of Albright hereditary osteodystrophy. Blood test results revealed hypocalcemia and hyperphosphatemia. Elevated PTH was also checked. There was no family history of endocrine or developmental problem. Her intelligence was normal, but she had inferior sociability at that time. Based on above, we diagnosed a rare case of paternal uniparental disomy of the long arm of chromosome 20 as the cause of PHP 1b by microsatellite marker test of chromosome 20.

A Case of Pseudohypoparathyroidism Type Ib Caused by Aberrant Methylation in the GNAS Complex Locus

Pseudohypoparathyroidism (PHP) is a rare disorder caused by genetic and epigenetic aberrations in the GNAS complex locus resulting in impaired expression of stimulatory G protein (Gsα). PHP type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to renal resistance to the parathyroid hormone, and is distinguished from PHP-Ia by the absence of osteodystrophic features. An 11-yr-old boy presented with poor oral intake and cramping lower limb pain after physical activity. Laboratory studies revealed hypocalcemia, hyperphosphatemia, and increased parathyroid hormone levels. The GNAS complex locus was evaluated using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Gain of methylation in the NESP55 domain and loss of methylation in the antisense (AS) transcript, XL, and A/B domains in the maternal allele were observed. Consequently, we present a case of PHP-Ib diagnosed using MS-MLPA.