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Nephrology (Carlton, Vic.) May 2024We describe a unique case of 27-year-old male with Gitelman syndrome (GS) co-exist with pseudohypoparathyroidism type 1B (PHP1B). The patient presented with a 5-year...
We describe a unique case of 27-year-old male with Gitelman syndrome (GS) co-exist with pseudohypoparathyroidism type 1B (PHP1B). The patient presented with a 5-year history of seizures, tetany, and numbness of the extremities. Further examinations showed recurrent hypokalemia, inappropriate kaliuresis, hypocalcemia, hyperphosphatemia, and elevated PTH levels. A novel variant of autosomal recessive GS (p.Val287Met SLC12A3) and a novel 492.3Kb deletion containing the whole of STX16, were discovered by a whole-exome sequencing. Following the diagnosis, calcitriol, calcium, and potassium supplements were started. Hematuria calcium and phosphorus levels, as well as blood potassium levels, have recovered and remained within normal ranges after 3 years of follow-up. Our findings have important consequences for supporting the idea that heterozygosity for variants have effects on the patients' clinical performance with autosomal recessive inheritance disorders. Further study is need for the putative effects of the variant. Likewise, further investigation with regards to the gene-gene interaction relations between GS and other electrolyte imbalance disorders is warranted.
Topics: Male; Humans; Adult; Gitelman Syndrome; Hypokalemia; Calcium; Solute Carrier Family 12, Member 3; Pseudohypoparathyroidism; Seizures; Water-Electrolyte Imbalance; Calcium, Dietary; Epigenesis, Genetic; Potassium
PubMed: 38233937
DOI: 10.1111/nep.14270 -
Journal of Pediatric Endocrinology &... May 2024Inactivating mutations result in varied phenotypes depending on parental origin. Maternally inherited mutations typically lead to hormone resistance and Albright's...
OBJECTIVES
Inactivating mutations result in varied phenotypes depending on parental origin. Maternally inherited mutations typically lead to hormone resistance and Albright's hereditary osteodystrophy (AHO), characterised by short stature, round facies, brachydactyly and subcutaneous ossifications. Paternal inheritance presents with features of AHO or ectopic ossification without hormone resistance. This report describes the case of a child with osteoma cutis and medulloblastoma. The objective of this report is to highlight the emerging association between inactivating germline mutations and medulloblastoma, aiming to shed light on its implications for tumor biology and promote future development of targeted surveillance strategies to improve outcomes in paediatric patients with these mutations.
CASE PRESENTATION
A 12-month-old boy presented with multiple plaque-like skin lesions. Biopsy confirmed osteoma cutis, prompting genetic testing which confirmed a heterozygous inactivating mutation. At 2.5 years of age, he developed neurological symptoms and was diagnosed with a desmoplastic nodular medulloblastoma, SHH molecular group, confirmed by MRI and histology. Further analysis indicated a biallelic loss of in the tumor.
CONCLUSIONS
This case provides important insights into the role of as a tumor suppressor and the emerging association between inactivating variants and the development of medulloblastoma. The case underscores the importance of careful neurological assessment and ongoing vigilance in children with known inactivating variants or associated phenotypes. Further work to establish genotype-phenotype correlations is needed to inform optimal management of these patients.
Topics: Humans; GTP-Binding Protein alpha Subunits, Gs; Male; Chromogranins; Medulloblastoma; Ossification, Heterotopic; Skin Diseases, Genetic; Infant; Cerebellar Neoplasms; Prognosis; Bone Diseases, Metabolic; Mutation
PubMed: 38529810
DOI: 10.1515/jpem-2023-0533 -
Indian Journal of Pediatrics Jan 2024
Topics: Humans; Pseudohypoparathyroidism; Genomic Imprinting; Mutation; DNA Methylation; GTP-Binding Protein alpha Subunits, Gs; Chromogranins
PubMed: 37548842
DOI: 10.1007/s12098-023-04787-3 -
The Journal of Clinical Endocrinology... Jun 2024Pseudohypoparathyroidism (PHP) refers to a group of rare hereditary disorders associated with resistance to parathormone (PTH) and other hormones now termed inactivating...
BACKGROUND
Pseudohypoparathyroidism (PHP) refers to a group of rare hereditary disorders associated with resistance to parathormone (PTH) and other hormones now termed inactivating PTH/PTHrP disorders (iPPSD). Hypercalcitoninemia has been seldom reported in small series. Our aim was to investigate the characteristics of hypercalcitoninemia in paediatric and adult patients with PHP/iPPSD.
METHODS
We retrospectively collected data from two cohorts from two European Endocrinology tertiary centers: the paediatric cohort comprised 88 children with available calcitonin (CT) measurements; the adult cohort included 43 individuals with simultaneous CT and PTH measurements.
RESULTS
In the paediatric cohort 65.9% had hypercalcitoninemia (median CT 15 ng/L); in the adult cohort 53.5% (mean CT 21.6 ng/L). There was no difference between CT in paediatric and adult population; we observed stable CT levels over a median follow-up of 134.5 months in adults. Notably, no correlations were detected between CT and PTH levels. Other etiologies of hypercalcitoninemia were excluded, adult patients underwent regular thyroid ultrasound (US) to screen for medullary thyroid cancer (MTC). We performed 20 calcium stimulation tests in adult patients. While there was a significant difference in basal and peak CT between our patients, healthy subjects and subjects with MTC, there was no difference with patients with C-cell hyperplasia.
CONCLUSIONS
This study underscores the common occurrence of hypercalcitoninemia in both paediatric and adult PHP/iPPSD patients, in particular with subtypes iPPSD2-iPPSD3. Furthermore, these patients show an hyperresponsiveness to calcium stimulation test falling between healthy subjects and patients with MTC. These findings contribute into the understanding of CT dynamics in the context of PHP/iPPSD.
PubMed: 38940443
DOI: 10.1210/clinem/dgae416