Case ReportsMolecular Diagnosis and Clinical Characterization of Pseudohypoparathyroidism Type-Ib in a Patient With Mild Albright’s Hereditary Osteodystrophy-Like Features, Epileptic Seizures, and Defective Renal Handling of Uric Acid
Section snippets
Case Report
A 17 year-old female patient was first admitted to our hospital with frequent absence seizures and hypocalcemia. The patient’s first episode as a tonic-clonic generalized seizure had occurred at the age of 14, at which time she was placed under treatment with valproate (3 × 500 mg). Although the patient was not compliant with the therapy for more than 1 week, she had a seizure-free period for 11 months. Subsequently, however, seizure episodes recurred and the patient was readmitted to the
Discussion
PHP refers to several distinct, but related, disorders in which end-organ resistance toward PTH is the most prominent feature. As a result of PTH resistance, patients with PHP have diminished serum concentrations of 1,25-[OH]2-vitamin D3, hypocalcemia, hyperphosphatemia, and increased PTH levels.
It has been documented that vitamin D deficiency can impair phosphaturic response to PTH.6., 12. Limited exposure to sunlight may have contributed to vitamin D deficiency in our patient.13 In addition,
Conclusion
Our findings correlate well with the previous reports regarding patients with AD-PHP-Ib. These include an increased fractional excretion of uric acid and hypouricemia, which has been reported previously only once in a kindred with this disorder. On the other hand, the presence of mild AHO-like features in the index case, whose diagnosis was confirmed by genetic analysis, raises the possibility that GNAS imprinting abnormalities might also lead to AHO features; however, it remains possible that
References (28)
- et al.
Paternal uniparental isodisomy of chromosome 20q—and the resulting changes in GNAS1 methylation—as a plausible cause of pseudohypoparathyroidism
Am J Hum Genet
(2001) Pseudohypoparathyroidism
- et al.
A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS
Am J Hum Genet
(2005) - et al.
The renal response to exogenous parathyroid hormone in treated pseudohypoparathyroidism
Bone
(1993) - et al.
Pseudohypoparatyroidism: new insights into old disease
Endocrinol Metab Clin North Am
(2000) - et al.
Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS
J Clin Invest
(2003) - et al.
Hormones and disorders of mineral metabolism
- et al.
The stimulatory G protein alpha-subunit Gs alpha is imprinted in human thyroid glands: implications for thyroid function in pseudohypoparathyroidism types 1A and 1B
J Clin Endocrinol Metab
(2003) - et al.
Positional dissociation between the genetic mutation responsible for pseudohypoparathyroidism type Ib and the associated methylation defect at exon A/B: evidence for a long-range regulatory element within the imprinted GNAS1 locus
Hum Mol Genet
(2001) - et al.
Dissociation between the effects of endogenous parathyroid hormone on adenosine 3′,5′-monophosphate generation and phosphate reabsorption in hypocalcemia due to vitamin D depletion: an acquired disorder resembling pseudohypoparathyroidism type II
J Clin Endocrinol Metab
(1985)
Effects of antiepileptic drugs on hormones
Epilepsia
Metacarpophalangeal length in the evaluation of skeletal malformation
Radiology
Distinct patterns of abnormal GNAS imprinting in familial and sporadic pseudohypoparathyroidism type IB
Hum Mol Genet
Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib
Nat Genet
Cited by (68)
Intracranial calcifications in pseudohypoparathyroidism type 1b: Report of four cases
2022, Endocrinologia, Diabetes y NutricionPTH resistance
2021, Molecular and Cellular EndocrinologyDeconstructing Fahr's disease/syndrome of brain calcification in the era of new genes
2017, Parkinsonism and Related DisordersCitation Excerpt :We collated information on 137 cases, either sporadic or from 34 families, with demographic and clinical characterisation found in Table 1. To further investigate the hypothesis that pseudohypoparathyroidism represents a comparable phenotype as a form of genetic brain calcification, we identified 18 publications with data on 20 patients which satisfied the inclusion criteria for review [12,15,45–60]. Apart from two families with two affected individuals in each, all cases of pseudohypoparathyroidism with cerebral brain calcification present were reported as sporadic.
Pseudohypoparathyroidism type Ib in 2015
2015, Annales d'EndocrinologieGenetic and epigenetic defects at the GNAS locus cause different forms of pseudohypoparathyroidism
2015, Annales d'EndocrinologieCitation Excerpt :Cependant, à partir des études de liaison génétique au sein de plusieurs grandes familles multigénérationnelles, il est devenu évident que la PHP1B est aussi causée par des mutations maternelles de GNAS, nommément de petites délétions au sein ou à proximité du locus GNAS [22–28] ; les mêmes délétions sur l’allèle paternel ne semblent entraîner aucune anomalie biologique. En outre, il a été démontré que les patients atteints de PHP1B peuvent montrer une résistance envers d’autres hormones que PTH, et que certains développent des traits de l’AHO, bien que ces anomalies soient moins prononcées que chez les patients atteints de PHP1A ou PPHP [29–31]. Les délétions identifiées chez des patients atteints de PHP1B sont associées à des modifications de la méthylation affectant soit seulement l’exon A/B de GNAS (délétions de STX16 [23,25,28] ou délétion comportant seulement l’exon NESP 27 de GNAS) ou toutes les quatre régions différemment méthylées de GNAS (délétions de GNAS comportant l’exon NESP et/ou les exons antisens 3 et 4 [24,26]).