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Practical Neurology Jun 2023
Topics: Humans; Metacarpal Bones; Basal Ganglia Diseases; Pseudohypoparathyroidism; Calcinosis; Basal Ganglia
PubMed: 36593114
DOI: 10.1136/pn-2022-003647 -
Current Opinion in Endocrinology,... Dec 2012To provide the reader with a review of contemporary literature describing the evolving understanding of the molecular pathobiology of pseudohypoparathyroidism (PHP). (Review)
Review
PURPOSE OF REVIEW
To provide the reader with a review of contemporary literature describing the evolving understanding of the molecular pathobiology of pseudohypoparathyroidism (PHP).
RECENT FINDINGS
The features of PHP type 1 reflect imprinting of the GNAS gene, which encodes the α subunit of the heterotrimeric G protein (Gα(s)) that couples heptahelical receptors to activation of adenylyl cyclase. Transcription of Gα(s) is biallelic in most cells, but is primarily from the maternal allele in some tissues (e.g. proximal renal tubules, thyroid, pituitary somatotropes, gonads). Patients with PHP 1a have heterozygous mutations within the exons of the maternal GNAS allele that encode Gα(s), whereas patients with PHP 1b have methylation defects in the GNAS locus that reduce transcription of Gα(s) from the maternal allele. In both PHP 1a and PHP 1b, paternal imprinting of Gα(s) leads to resistance to parathyroid hormone and TSH. Although brachydactyly is characteristic of PHP 1a, it is sometimes present in patients with PHP 1b.
SUMMARY
Molecular studies enable a distinction between PHP 1a and PHP 1b, with different mechanisms accounting for Gα(s) deficiency. Clinical overlap between these two forms of PHP type 1 is likely due to the variable levels of Gα(s) activity expressed in specific cell types.
Topics: Animals; Chromogranins; DNA Methylation; Epigenomics; GTP-Binding Protein alpha Subunits, Gs; Genomic Imprinting; Humans; Mice; Mice, Knockout; Mutation; Pseudohypoparathyroidism; Thyroid Gland
PubMed: 23076042
DOI: 10.1097/MED.0b013e32835a255c -
Seminars in Musculoskeletal Radiology Dec 2002Pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO) are not interchangeable terms. AHO describes a constellation of physical features,... (Review)
Review
Pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO) are not interchangeable terms. AHO describes a constellation of physical features, including short adult stature, obesity, brachydactyly, and ectopic ossifications. PHP means end-organ resistance to PTH and is subclassified into types Ia, Ib, and Ic and type II. Pseudopseudohypoparathyroidism (PPHP) is a term used for individuals with AHO who have normal end-organ responses to PTH. Both the PHPIa and PPHP forms of AHO result from heterozygous deactivating mutations in the GNAS1 gene associated with a 50% reduction in bioactivity of the Gsalpha protein that it encodes. The GNAS1 gene is subject to tissue-specific genomic imprinting. Patients with mutations on their maternally derived allele are likely to have associated PHPIa, whereas mutations on the paternal allele usually cause PPHP. Isolated PTH resistance (PHPIb) can result from mutations within the GNAS1 gene but is more commonly caused by epigenetic imprinting abnormalities affecting the upstream exon 1A. The causes of PHP type Ic and PHP type II are not yet clear, and the latter is likely to be heterogeneous.
Topics: Diagnosis, Differential; Fibrous Dysplasia, Polyostotic; GTP-Binding Protein alpha Subunits, Gs; Heterozygote; Humans; Mutation; Pseudohypoparathyroidism; Radiography
PubMed: 12541184
DOI: 10.1055/s-2002-36726 -
The Journal of the Association of... Jan 2023Symptomatic hypocalcemia has a variety of underlying etiologies,with hypoparathyroidism and vitamin D deficiency being the most common. However,rarer etiologies such as...
INTRODUCTION
Symptomatic hypocalcemia has a variety of underlying etiologies,with hypoparathyroidism and vitamin D deficiency being the most common. However,rarer etiologies such as pseudohypoparathyroidism, as is present in the current case, should not be overlooked. Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by parathyroid hormone (PTH) resistance. The diagnosis of this rare genetic condition is often delayed,due to its myriad presentations,leading to an initially inappropriate approach and therapy.
MATERIALS
A 19-year-old male,K/C/O seizure disorder since 18 years,presented to ER in generalized convulsive status epilepticus since 2 hours.Developmentally he had poor growth spurt. No h/o trauma, fever, vomiting, headache. Patient continued to have seizures occasionally despite being compliant to Tab Sodium Valproate 250mg BD.O/E: Patient was drowsy but arousable. He had short stature.Height-35 kg, Weight-136 cm and BMI 18.92 kg/m2.Bilateral cataractous lens+. Examination of limbs revealed brachydactyly of the fingers and fourth toes. Chvostek and Trousseau signs were positive. Knuckle knuckle Dimple Dimple Sign+ Result: ECG showed showed prolonged QT interval. Blood investigations showed Serum calcium-5.8, Serum phosphorus-8.7, iPTH-193, TSH-15.4. MRI brain revealed diffuse bilateral calcifications of basal ganglia. Given the clinical,radiographic and laboratory findings, diagnoses of PHP type Ia with primary hypothyroidism was made.Patient was admitted to wards,hypocalcemia corrected with intravenous and oral calcium and vitamin D.Discharged on 50 ug levothyroxine, oral calcium, vitamin D3 oral solution weekly. The patient is being followed up at half monthly intervals and has remained seizure free since discharge.
CONCLUSION
PHP type Ia (GNAS gene mutation) is the most common form of PHP and associated with Albright's hereditary osteodystrophy (AHO), resistance to multiple hormones. This case stresses the pivotal role of a complete biochemical investigation of the calcium phosphate metabolism in every References Melmed S, Koenig R, Rosen C, Auchus R, Goldfine A. Williams textbook of endocrinology: South Asia edition, 2 vol set-E-book. Elsevier India; 2020 Jun 30. Mantovani G, Bastepe M, Monk D, De Sanctis L, Thiele S, Ahmed SF, Bufo R, Choplin T, De Filippo G, Devernois G, Eggermann T. Recommendations for diagnosis and treatment of pseudohypoparathyroidism and related disorders: an updated practical tool for physicians and patients. Hormone research in paediatrics. 2020;93(3):182-96.
Topics: Humans; Male; Child; Young Adult; Adult; Calcium; Hypocalcemia; Pseudohypoparathyroidism; Vitamin D; Vitamins; Calcinosis; Calcium, Dietary
PubMed: 37116029
DOI: No ID Found -
Kathmandu University Medical Journal... 2022Hypocalcaemia of various origin can be manifested by paresthesia, muscle cramps, muscle weakness, syncope, convulsions and even severe psychomotor retardation. Such...
Hypocalcaemia of various origin can be manifested by paresthesia, muscle cramps, muscle weakness, syncope, convulsions and even severe psychomotor retardation. Such symptoms can be initially considered as signs of epilepsy. We present a 12- year old boy with partial seizures and basal ganglia calcifications, initially diagnosed as having Fahr´s disease and epilepsy, where severe hypocalcaemia, due to genetically confirmed pseudohypoparathyroidism type Ib was the underlying cause. Excellent clinical improvement was observed after calcium and vitamin D therapy. The basal ganglia calcifications were secondary due to chronic hypocalcaemia, therefore the appropriate diagnosis was pseudohypoparathyroidism type Ib with Fahr´s syndrome, but not Fahr´s disease. In conclusion, the serum evaluation of minerals, especially calcium and phosphate, should be performed in all patients with convulsions, cramps and psychomotor retardation. This is essential in arriving at a proper diagnosis and early initiation of appropriate treatment.
Topics: Male; Humans; Child; Hypocalcemia; Calcium; Pseudohypoparathyroidism; Seizures; Epilepsy
PubMed: 37042384
DOI: No ID Found -
Polski Tygodnik Lekarski (Warsaw,...
Topics: Humans; Pseudohypoparathyroidism
PubMed: 1669165
DOI: No ID Found -
Anales de Pediatria Feb 2019Since Albright and co-workers described pseudohypoparathyroidism in 1942 as the combined presence of hypocalcaemia and hyperphosphataemia associated with the existence...
Since Albright and co-workers described pseudohypoparathyroidism in 1942 as the combined presence of hypocalcaemia and hyperphosphataemia associated with the existence of tissue resistance to parathyroid hormone (PTH) action upon normal renal function, great advances have been made in the clinical and genetic profile of patients affected by this condition. Furthermore, not only have genetic bases of pseudohypoparathyroidism been unravelled, but also variants in other genes involved in the PTH/PTHrP signalling pathway through Gsα, have been identified as the cause of diseases that share clinical features with pseudohypoparathyroidism. In the paediatric setting, the first symptoms suggesting the impairment of this signalling pathway are the presence of subcutaneous ossifications, brachydactyly and/or early onset obesity, followed by the possible development of PTH resistance. This clinical suspicion should be confirmed by an accurate molecular diagnosis to allow for coordinated multidisciplinary clinical management. Among the features of this group of disorders, physicians should pay attention to evaluation of PTH and/or thyrotropin (TSH) resistance at diagnosis and throughout follow-up, as well as growth hormone deficiency, hypogonadism, skeletal deformities, dental impairment, obesity, insulin resistance, impaired glucose tolerance or type2 diabetes mellitus and hypertension, as well as ectopic ossifications (either subcutaneous or affecting deeper tissues) and impairment of neurocognitive development.
Topics: Child; Diagnosis, Differential; Genetic Markers; Humans; Pediatrics; Pseudohypoparathyroidism
PubMed: 30591400
DOI: 10.1016/j.anpedi.2018.11.014 -
Presse Medicale (Paris, France : 1983) Sep 2017Chronic calcipenia related to hypo- and pseudohypoparathyroidism favors trophic complications, especially expressed on the buccal cavity. Correlated with early onset of... (Review)
Review
Chronic calcipenia related to hypo- and pseudohypoparathyroidism favors trophic complications, especially expressed on the buccal cavity. Correlated with early onset of the disease and imperfect correction of the metabolic disorders, retardation to appearance and implantation of teeth are observed. The buccal signs often are the most immediately visible expression of the disease. They are painful and disabling. Other acute expressions reflect the neuromuscular hyperexcitability related to tetany. Finally, some etiologies determine specific damage, as in Di George's, HDR syndromes or in Albright's osteodystrophia.
Topics: Diagnosis, Differential; Humans; Hypocalcemia; Hypoparathyroidism; Mouth Diseases; Pseudohypoparathyroidism; Statistics as Topic; Tetany; Tooth Diseases
PubMed: 28483283
DOI: 10.1016/j.lpm.2017.04.002 -
The Journal of Clinical Endocrinology... Sep 2003
Review
Topics: Chromogranins; GTP-Binding Protein alpha Subunits, Gs; Heterotrimeric GTP-Binding Proteins; Hormones; Humans; Nerve Tissue Proteins; Protein Subunits; Pseudohypoparathyroidism
PubMed: 12970261
DOI: 10.1210/jc.2003-031271 -
Hormone and Metabolic Research =... Jan 2022Luo et al. 1 reported two cases of autosomal dominant pseudohypoparathyroidism type 1B (AD-PHP1B) and reviewed literature about the genetic and epigenetic...
Luo et al. 1 reported two cases of autosomal dominant pseudohypoparathyroidism type 1B (AD-PHP1B) and reviewed literature about the genetic and epigenetic characteristics of AD-PHP1B. Pseudohypoparathyroidism (PHP) is a cluster of heterogeneous diseases characterized by hypocalcemia and hyperphosphatemia due to resistance to parathyroid hormone (PTH). PHP1B almost results from methylation abnormalities of the maternal differentially methylated regions (DMRs) and can be divided into sporadic PHP1B and AD-PHP1B 1. As mentioned in this article 1, AD-PHP1B is caused by heterozygous maternal deletions within GNAS or STX16, which are associated with loss of methylation at the A/B DMR alone or at all maternally methylated GNAS exons. While sporadic PHP1B remains unclear at the molecular level, except for approximately 10% of the patients caused by paternal uniparental isodisomy or heterodisomy involving chromosome 20q (patUPD20q) 2. Here, we would like to present a rare case of sporadic PHP1B occurring in association with hypokalemia.
Topics: Adolescent; Female; Humans; Hypokalemia; Pseudohypoparathyroidism
PubMed: 34327681
DOI: 10.1055/a-1528-7471