Severe combined immunodeficiency (SCID) presenting in childhood, with agammaglobulinemia, associated with novel compound heterozygous mutations in DCLRE1C

Publication date: Available online 7 January 2019

Source: Clinical Immunology

Author(s): Mikael Sundin, Per Marits, Kim Ramme, Antonios G.A. Kolios, Jakob Nilsson

Abstract

Severe combined immunodeficiency (SCID) can be caused by deleterious mutations in DCLRE1C, leading to deficient non-homologous end joining by compromising the function of the Artemis protein. This impairs the process of V(D)J recombination of the T- and B-cell receptors and typically results in radiosensitive T⁻, B⁻, NK⁺ SCID presenting during the first months of life. We present a case of a 3-year-old girl with two novel compound heterozygous variants in DCLRE1C (c.58G>C and c.374A>C) that were associated with marked reduced numbers of peripheral T- and B-cells and undetectable total serum IgG. Despite the severe laboratory phenotype, the patient had a normal development, albeit failure to thrive (−2.5 to −3 SD), during her first years of life including day-care attendance at preschool for 1.5 years. After being diagnosed with pneumonia the clinical picture of SCID was recognized and the girl successfully underwent hematopoietic stem-cell transplantation.

http://bit.ly/2Riuykg

Early 18 F-FDOPA PET/CT imaging after carbidopa premedication as a valuable diagnostic option in patients with insulinoma

Abstract

Purpose

Data on the diagnostic value of ¹⁸F-FDOPA PET/CT in patients with insulinoma are limited and are focused on small patient populations explored using different PET/CT protocols and the inconsistent use of carbidopa premedication. The aim of this study was to improve the current knowledge about the diagnostic value of ¹⁸F-FDOPA PET/CT combined with oral carbidopa premedication and early pancreatic imaging for tumour localization in patients with insulinoma-related hyperinsulinaemic hypoglycaemia (HH). The relationships among ¹⁸F-FDOPA quantitative uptake parameters, insulin secretion and tumour pathological features were also investigated.

Methods

Of 34 patients with suspicion of insulinoma-related HH examined by dual time-point carbidopa-assisted ¹⁸F-FDOPA PET/CT, 24 with histologically proven insulinoma were retrospectively included. One patient underwent two PET/CT examinations for relapsing insulinoma after surgical excision. Thus, 25 preoperative ¹⁸F-FDOPA PET/CT studies were finally retained and analysed. All studies were performed under carbidopa premedication (200 mg orally, 1–2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after ¹⁸F-FDOPA injection) over the upper abdomen and a delayed whole-body acquisition starting 20–30 min later. The cytological and/or histopathological diagnosis of insulinoma was the diagnostic standard of truth.

Results

¹⁸F-FDOPA PET/CT localized insulinoma in 21 of the 25 studies, leading to a primary lesion detection rate of 84%. Four lesions (19%) were detected only on early acquisitions. The false-negative tumour detection rates were, respectively, 22% and 12.5% in patients receiving and not receiving treatment for hypoglycaemic symptoms at the time of PET/CT. In benign insulinomas, the early maximum standardized uptake value (SUVmax) was significantly higher than the delayed SUVmax. Compared to the 21 benign lesions, four malignant insulinomas showed significantly higher ¹⁸F-FDOPA uptake. Lesion size, fasting-end insulin and C-peptide levels correlated with tumour ¹⁸F-FDOPA uptake, dopaminergic tumour volume and metabolic burden.

Conclusion

The present study showed that ¹⁸F-FDOPA PET/CT combined with carbidopa premedication and early pancreatic acquisitions is a valuable diagnostic option in patients with insulinoma when GLP1R-based imaging is not available. The results also provide new insights into the relationships between tumour secretion and imaging phenotype in insulinomas.

http://bit.ly/2scvVBO

Bilateral cochlear implantation is regarded as very beneficial: results from a worldwide survey by online questionnaire

Abstract

Purpose

Bilateral cochlear implant (CI) provision is now widely regarded as the most beneficial hearing intervention for acceptable candidates. This study sought to determine if a number of well-regarded hearing professionals at highly reputable clinics shared similar practices and beliefs regarding bilateral CI provision, use, and rehabilitation in children and adults.

Methods

An 11-question online questionnaire was created and distributed to all 27 clinics in the HEARRING group. Questions 1–5 asked for facts; questions 6–11 asked for opinions.

Results

20 completed questionnaires were returned. All 20 respondents reported that their clinics perform bilateral cochlear implantation in children; 18 do so in adults. Regarding the fact-based questions, bilateral CI provision is more commonly performed and more likely to be reimbursed in children than in adults. Children are also much more likely to be implanted simultaneously than are adults. Regarding the opinion-based questions, respondents gave broadly similar answers. Communication between the CIs and speech coding strategies specifically developed for bilateral CI users were regarded as the two future technologies that would most enhance the benefit of bilateral CI use.

Conclusions

Most clinics in the HEARRING group are very familiar with bilateral CI provision and hold similar opinions on its results and benefits. Hopefully the results described herein will lead to a greater acceptance and regular reimbursement of bilateral CI provision, especially in adults.

http://bit.ly/2scwews

Is there a relationship between Onodi cell and optic canal?

Abstract

Objectives

We investigated the relationship between Onodi cells and optic canal by paranasal sinus computed tomography (PNSCT).

Methods

In this retrospective study, 508 PNSCT (265 males and 243 females) was examined. Onodi cell presence, pneumatization types, optic canal types; and also sphenoid sinusitis and anterior clinoid process pneumatization were evaluated.

Results

The prevalence of Onodi cells was 21.2% of the patients. Onodi cells were observed 40.7% on the right side and 25.9% on the left side. In 33.4% of the patients, bilateral Onodi cells were present. Male/Female ratio was 24.5%/17.6%. Onodi cell types were detected as Type I > Type II > Type III bilaterally. There was a positive correlation between the right and left Onodi cell types (p < 0.05). Optic canal types were detected as Type IV > Type I > Type II > Type III. bilaterally. There was a positive correlation between right and left optic canal types. Onodi cell presence and ACP pneumatization were found as statistically significant (p < 0.05). In 65.5% of the patients, Onodi cells and ACP pneumatization were absent. ACP pneumatization was present in 35.4% of the cases. In nine cases, bilateral Onodi cells and ACP pneumatization were detected. Sphenoid sinusitis was detected in 11.4% of Type I and 13.8% of the Type II Onodi cells on the right side. On the left side, it was detected in 12.9% of the Type I and 19.0% of Type II Onodi cells.

Conclusion

Identification of Onodi cell is very important clinically because of its proximity to optic nerve canal. We concluded that type IV Onodi–optic canal relationship was the most common finding in our study. Onodi cell presence and their patterns of pneumatization must be evaluated on PNSCT preoperatively to avoid optic canal damage.

http://bit.ly/2LT9bjj

First case of Rubinstein–Taybi syndrome with desquamation associated with a novel mutation in the bromodomain of the CREBBP gene

Summary

Rubinstein–Taybi syndrome (RSTS) is a rare congenital disorder, mainly characterized by postnatal growth retardation, intellectual disability, and facial and limb abnormalities. Although not considered as characteristic manifestations, numerous cutaneous anomalies have also been reported in patients with RSTS while there has been no report of desquamation so far in any patients with RSTS. We report an unusual case of RSTS in an 8‐year‐old boy who presented with the typical facial and limb abnormalities of RSTS accompanied with apparent hirsutism and desquamation, but without apparent intellectual disability. Whole exome sequencing identified a novel mutation in the bromodomain of CREBBP (c.3503A>G, p.N1168S), which was further confirmed by targeted Sanger sequencing in comparison with healthy controls. Our findings expand the spectra of genetic mutations and clinical presentations associated with RSTS, and underline the importance of maintaining high awareness of rare presentations and diagnostic difficulties in management of rare genetic diseases such as RSTS.

http://bit.ly/2CTm61Z

The protean manifestations of RASA1 gene mutation

http://bit.ly/2TvSJrZ

First case of Rubinstein–Taybi syndrome with desquamation associated with a novel mutation in the bromodomain of the CREBBP gene

Summary

Rubinstein–Taybi syndrome (RSTS) is a rare congenital disorder, mainly characterized by postnatal growth retardation, intellectual disability, and facial and limb abnormalities. Although not considered as characteristic manifestations, numerous cutaneous anomalies have also been reported in patients with RSTS while there has been no report of desquamation so far in any patients with RSTS. We report an unusual case of RSTS in an 8‐year‐old boy who presented with the typical facial and limb abnormalities of RSTS accompanied with apparent hirsutism and desquamation, but without apparent intellectual disability. Whole exome sequencing identified a novel mutation in the bromodomain of CREBBP (c.3503A>G, p.N1168S), which was further confirmed by targeted Sanger sequencing in comparison with healthy controls. Our findings expand the spectra of genetic mutations and clinical presentations associated with RSTS, and underline the importance of maintaining high awareness of rare presentations and diagnostic difficulties in management of rare genetic diseases such as RSTS.

http://bit.ly/2CTm61Z