scholarly journals Performance of the pro-FHH score in a delayed diagnosis of familial hypocalciuric hypercalcemia type-1

Author(s):  
Akuffo Quarde ◽  
Chris Y. Fan ◽  
Jennifer Leonhard
2020 ◽  
Vol 105 (5) ◽  
pp. 1393-1400
Author(s):  
Poonam Dharmaraj ◽  
Caroline M Gorvin ◽  
Astha Soni ◽  
Nick D Nelhans ◽  
Mie K Olesen ◽  
...  

Abstract Context Familial hypocalciuric hypercalcemia type 1 (FHH1) is caused by loss-of-function mutations of the calcium-sensing receptor (CaSR) and is considered a benign condition associated with mild-to-moderate hypercalcemia. However, the children of parents with FHH1 can develop a variety of disorders of calcium homeostasis in infancy. Objective The objective of this work is to characterize the range of calcitropic phenotypes in the children of a mother with FHH1. Methods A 3-generation FHH kindred was assessed by clinical, biochemical, and mutational analysis following informed consent. Results The FHH kindred comprised a hypercalcemic man and his daughter who had hypercalcemia and hypocalciuria, and her 4 children, 2 of whom had asymptomatic hypercalcemia, 1 was normocalcemic, and 1 suffered from transient neonatal hypocalcemia and seizures. The hypocalcemic infant had a serum calcium of 1.57 mmol/L (6.28 mg/dL); normal, 2.0 to 2.8 mmol/L (8.0-11.2 mg/dL) and parathyroid hormone of 2.2 pmol/L; normal 1.0 to 9.3 pmol/L, and required treatment with intravenous calcium gluconate infusions. A novel heterozygous p.Ser448Pro CaSR variant was identified in the hypercalcemic individuals, but not the children with hypocalcemia or normocalcemia. Three-dimensional modeling predicted the p.Ser448Pro variant to disrupt a hydrogen bond interaction within the CaSR extracellular domain. The variant Pro448 CaSR, when expressed in HEK293 cells, significantly impaired CaSR-mediated intracellular calcium mobilization and mitogen-activated protein kinase responses following stimulation with extracellular calcium, thereby demonstrating it to represent a loss-of-function mutation. Conclusions Thus, children of a mother with FHH1 can develop hypercalcemia or transient neonatal hypocalcemia, depending on the underlying inherited CaSR mutation, and require investigations for serum calcium and CaSR mutations in early childhood.


2008 ◽  
Vol 94 (2) ◽  
pp. 151-152 ◽  
Author(s):  
P C B Sundaram ◽  
E Day ◽  
J M W Kirk

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Noriaki Nishihara ◽  
Shunsuke Tachibana ◽  
Hajime Sonoda ◽  
Michiaki Yamakage

Abstract Background Myotonic dystrophy is a disorder affecting multiple organs including skeletal muscles and causes respiratory failure. We describe a patient who developed respiratory failure, with delayed diagnosis of myotonic dystrophy type 1 as the cause. Case presentation A 62-year-old woman developed acute onset of dyspnea after showing hypertension and tachycardia and was transported to our hospital. On arrival at our institution, SpO2 was 80% with a non-rebreather mask. With a diagnosis of acute phase heart failure, she underwent tracheal intubation. However, weaning from the respirator was difficult in the intensive care unit (ICU). A detailed interview revealed that her brother was affected with myotonic dystrophy type 1. She was also diagnosed with myotonic dystrophy type 1 by a genetic test. Conclusions Taking a careful past and family history and prompt genetic testing is required on suspicion of neuromuscular diseases in a patient with respiratory failure by an unknown cause.


2020 ◽  
Vol 106 (6) ◽  
pp. 734-747 ◽  
Author(s):  
Ridge Dershem ◽  
Caroline M. Gorvin ◽  
Raghu P.R. Metpally ◽  
Sarathbabu Krishnamurthy ◽  
Diane T. Smelser ◽  
...  

2019 ◽  
Vol 27 ◽  
pp. 49-54
Author(s):  
Piotr Bogucki ◽  
Ewa Nagańska ◽  
Marta Jurek ◽  
Dorota Hoffman-Zacharska ◽  
Anna Kutkowska-Kaźmierczak ◽  
...  

2021 ◽  
Author(s):  
◽  
Gemma Williams ◽  
Ross McLean ◽  
Jo-Fen Liu ◽  
Timothy Ritzmann ◽  
...  

AbstractBackgroundThe COVID-19 pandemic led to changes in patterns of presentation to Emergency Departments (ED). Child health professionals were concerned that this could contribute to the delayed diagnosis of life-threatening conditions, including childhood cancer (CC) and type 1 diabetes (T1DM). Our multicentre, UK-based service evaluation assessed diagnostic intervals and disease severity for these conditions.MethodsWe collected presentation route, timing and disease severity for children with newly diagnosed CC in three principal treatment centres, and T1DM in four centres between 1stJanuary – 31st July 2020 and the corresponding period in 2019. We assessed the impact of lockdown on total diagnostic interval (TDI), patient interval (PI), system interval (SI) and disease severity.FindingsFor CCs and T1DM, the route to diagnosis and severity of illness at presentation were unchanged across all time periods. Diagnostic intervals for CCs during lockdown were comparable to that in 2019 (TDI 4.6, PI 1.1 and SI 2.1 weeks), except for an increased PI in Jan-Mar 2020 (median 2.7 weeks). Diagnostic intervals for T1DM during lockdown were similar to that in 2019 (TDI 16 vs 15 and PI 14 vs 14 days), except for an increased PI in Jan-Mar 2020 (median 21 days).InterpretationThere is no evidence of diagnostic delay or increased illness severity for CC or T1DM, during the first phase of the pandemic across the participating centres. This provides reassuring data for children and families with these life-changing conditions.Research in ContextEvidence before this studyThis project was initiated after the first national lockdown in March 2020 during COVID-19 pandemic in the UK. At the design stage, Medline was searched (with no language limit), using the keywords ((Cancer) OR (neoplasm) OR (Type 1 diabetes mellitus)) AND ((Covid-19) OR (SARS-CoV-2) OR (Pandemics)) AND ((Emergency department attendances) OR (diabetes ketoacidosis) OR (Delayed diagnosis) OR (interval) OR (wait)) to identify publications reporting the impact of the pandemic and public health measures on both overall and paediatric healthcare services. Significant changes in service utilisation in the UK were reported following the commencement of the first lockdown, including a 49% reduction in emergency department attendances in the week following the lockdown; and two adult studies reported that referral via the urgent two-week wait cancer referral diagnoses decreased by 84% from Mar-May and 60% in June 2020. As for Type 1 diabetes (T1DM), a 30 patient UK-study reported an increase in newly diagnosed T1DM during the first six weeks of lockdown. Increased proportions of severe diabetic ketoacidosis (DKA) at presentation were also reported in an Italian survey involving 53 paediatric diabetes centres. Through the search we identified a need for multi-centre, more thorough assessment on referral pathways, time taken from symptom onset to diagnosis, and its association with severity at presentation for children diagnosed with life-changing conditions during the national lockdown.Added value of this studyOur findings suggest that the first national lockdown in the UK were not associated with delayed diagnosis of childhood cancer or type 1 diabetes at participating centres. This provides reassuring information for children and families with these life-changing conditions.ImplicationWe believe that our study can play a key role in allaying parental and professional concern. it is important to establish whether subsequent public health measures have impacted the diagnostic interval in the context of an evolving backlog of patient referrals across the UK.


2008 ◽  
Vol 159 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Yasunaga Ono ◽  
Naohisa Oda ◽  
Shin Ishihara ◽  
Atsushi Shimomura ◽  
Nobuki Hayakawa ◽  
...  

Context and objectiveArterial stimulation and venous sampling (ASVS) is an important technique for localizing insulinoma. The principle behind ASVS is that insulin secretion is promoted from insulinoma cells by the injection of calcium into the insulinoma-feeding artery. However, the mechanism for ASVS-induced insulin secretion remains unclear. Both insulinoma and familial hypocalciuric hypercalcemia (FHH) are rare diseases. This study reports on a case in which both of these diseases occur concurrently.Design and patientThe patient with FHH also suffered from insulinoma. We reasoned that insulin secretion for ASVS is dependent on the calcium-sensing receptor (CaSR). ASVS was performed on this patient. The expression of the CaSR protein and corresponding mRNA were confirmed.ResultsNo significant changes in the plasma levels of insulin and C-peptide were observed during ASVS. The patient was clinically diagnosed as having FHH. We confirmed that a mutation in the CaSR gene was present in the genomic DNA of this patient and that there were no mutations in the multiple endocrine neoplasia type 1 gene. In addition, expression of both CaSR mRNA and CaSR protein was confirmed in the insulinoma samples.ConclusionThese results suggest that the CaSR gene is involved in ASVS-induced insulin secretion.


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