Identification of a novel KAT6A variant in an infant presenting with facial dysmorphism and developmental delay: a case report and literature review

Background Arboleda-Tham syndrome (ARTHS), caused by a pathogenic variant of KAT6A, is an autosomal dominant inherited genetic disorder characterized by various degrees of developmental delay, dysmorphic facial appearance, cardiac anomalies, and gastrointestinal problems. Case presentation A baby presented multiple facial deformities including a high arched and cleft palate, with philtral ridge and vermilion indentation, a prominent nasal bridge, a thin upper lip, low-set ears, an epicanthal fold, and cardiac malformations. Whole exome sequencing (WES) revealed a heterozygous nonsense mutation in exon 8 of the KAT6A gene (c.1312C>T, p.[Arg438*]) at 2 months of age. After a diagnosis of ARTHS, an expressive language delay was observed during serial assessments of developmental milestones. Conclusions In this study, we describe a case with a novel KAT6A variant first identified in Korea. This case broadens the scope of clinical features of ARTHS and emphasizes that WES is necessary for early diagnosis in patients with dysmorphic facial appearances, developmental delay, and other congenital abnormalities.

Serial assessments of anterior pituitary hormones in a case of mixed histiocytosis representing Langerhans cell histiocytosis overlapping with Erdheim–Chester disease

Summary A 61-year-old man developed central diabetes insipidus caused by mixed histiocytosis (MH) representing Langerhans cell histiocytosis overlapping with Erdheim–Chester disease. Bone, skin, vascular, and retroperitoneal involvements were also observed. Dynamic hormonal testing showed normal responses for anterior pituitary hormones, except for impaired secretion of growth hormone (GH). MRI of the brain showed thickening of the pituitary stalk with slightly reduced signal hyperintensity in the posterior pituitary lobe on T1-weighted imaging. During 2 years of follow-up without radical treatment for MH, imaging studies suggested extension of vascular and retroperitoneal involvements. In contrast, brain MRI did not show any particular interval changes, except for the disappearance of hyperintense signalling in the posterior pituitary lobe. Moreover, no other anterior pituitary dysfunctions beyond GH deficiency emerged during the 2 years of follow-up. The natural history of MH in this case is described, focusing on serial assessments of pituitary functions using dynamic tests. Learning points Erdheim–Chester disease and Langerhans cell histiocytosis overlapping as MH was described, focusing on pituitary functions. MH caused both GH deficiency and central diabetes insipidus. Despite a lack of radical therapy for MH, no other anterior pituitary dysfunctions emerged for 2 years. Radiological images showed no particular interval changes in pituitary stalk lesions, while vascular and retroperitoneal involvements extended.

Pulmonary Function and Chest CT in Patients Recovering From COVID-19 Pneumonia

Background: COVID-19 is a new and highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a paucity of data regarding long-term CT findings and pulmonary function in COVID-19 survivors. The aim of this study was to investigate the influence of COVID-19 pneumonia on pulmonary function and chest high-resolution computed tomography (CT) in convalescent patients. Methods: A retrospective study of COVID-19 pneumonia patients in the Beijing Youan Hospital, Capital Medical University, was conducted. Serial assessments, including pulmonary volumes (TLC), spirometry (VC, FVC, FEV1), pulmonary diffusing capacity for carbon monoxide (DLCO, DLCO/VA), and chest high-resolution CT were collected 3 months after discharge. Results: Forty-six patients completed the serial assessments. There were 38 non-severe and 8 severe cases. Abnormalities were detected in pulmonary function tests in 17 patients (37.8%). One (2.2%), 2 (4.3%), and 17 (37.8%) patients had FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. Twenty-eight patients (60.9%) had abnormal CT findings. Compared with patients with non-severe disease, those with severe disease had higher chest CT scores but a similar incidence of DLCO impairment. Similarly, patients who received glucocorticoids had higher chest CT scores but a similar incidence of DLCO impairment than those in the nonglucocorticoid group. Conclusions: Three months after discharge from the hospital, impaired diffusing capacity and CT abnormalities were detected in more than one third of COVID-19 patients. Compared with patients with non-severe disease, those with severe illness had a higher incidence of lung imaging abnormalities and similar lung function impairment.

Feasibility of using a computerized food frequency questionnaire (FFQ) to assess dietary patterns in patients with advanced gastrointestinal (GI) malignancies.

465 Background: Identification of poor dietary patterns is important for the optimal management of patients with metastatic GI malignancies who suffer from high rates of malnutrition and sarcopenia which are associated with increased rates of treatment-related toxicity and worsened survival. Dietary records or recall methods and FFQs are available but have high patient burden and are seldom utilized in oncology settings outside of formal nutritional consultations. Thus, we evaluated the feasibility of conducting serial assessments of dietary patterns using a novel computerized FFQ technology. Methods: Assessments of diet using the computerized FFQ, nutritional status (NUTRISCORE), QOL and anorexia/cachexia burden (FAACT), anxiety/depression (HADS) and taste burden were done at the time of initiation of first-line chemotherapy (baseline) and 3 months later. The FFQ was done independently either at home on personal computer after visit or via iPad in infusion room. Dietary quality was defined by the Healthy Eating Index 2010 (HEI) score, which was automatically calculated by the computerized FFQ software. Feasibility was defined as at least 70% of patients completing baseline and 3-month assessments. Spearman’s correlations were used to determine associations between measures. Results: 29 patients with advanced (metastatic or unresectable) GI cancers were enrolled and 23 completed the baseline FFQ (8 colorectal, 5 pancreas, 5 gastroesophageal, 5 other). Median age was 58 (20-78) with M:F ratio of 10:13. The overall completion rate of baseline and 3-month assessments was 81.8%, meeting the pre-defined feasibility criteria. The mean baseline HEI score was 65 (range 38-88). Of patients who completed both baseline and 3-month assessments, the mean HEI score remained stable at 58 with changes in specific HEI components including a 20% decline in the seafood and plant protein score and a 13% decline in the whole grain score and small improvements in other areas (e.g. empty calories, dairy). There were no significant correlations between baseline HEI score and other assessments. Conclusions: It is feasible to use a computerized FFQ to assess for longitudinal changes in eating patterns and dietary quality in patients with advanced GI cancers, particularly when patients can complete the assessments during chemotherapy infusions. Preliminary findings also suggest that the FFQ can be helpful for highlighting areas in which diet quality could be improved. Additional analysis of other computerized FFQ data (e.g. macro/micronutrient consumption) is ongoing.

Impact of Coronavirus Disease 2019 on Pulmonary Function in Early Convalescence Phase

Objective: This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase.Methods: A prospective retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-minute walking distance (6MWD) and high resolution CT being collected at 30 days after discharged.Results: 57 patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p=0.019), higher lung total severity score（TSS）and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit.Conclusion: Impaired diffusing-capacityDeclining DLCO, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.

Serial Assessment of Body Fat and Fat-Free Mass Accretion in Very Preterm Infants: A Randomized Trial

Objectives To incorporate assessment of body composition in the routine care of preterm infants to guide feeding practices before and after hospital discharge. Methods Very preterm infants with gestational ages between 29 and 32 weeks of gestation were included. Infants with gastrointestinal or neurologic malformations and terminal illness needing to limit or withhold support were excluded. All study participants were eligible for serial assessments of body composition between birth and 32 weeks PMA, at 36 weeks PMA or hospital discharge, and at 3 months of corrected age. Infants randomly assigned to the intervention group had the information about infant body composition available to the clinicians caring for them (including reference data). Infants randomly assigned to the control group also underwent serial assessments, but this information on infant body composition was not shown to the clinicians caring for them. The primary outcome was % body fat (%BF) estimated by air displacement plethysmography. Results Fifty very preterm infants were randomized. Mean birthweight of study participants was 1387 g +/– SD 283 and median gestational age at birth was 30 weeks (IQR: 30 – 31). Sociodemographic characteristics did not differ between groups. Mean %BF between birth and 32 weeks PMA (n = 45) was 6 +/– 4, mean %BF at 36 weeks PMA (n = 35) was 14 +/– 4, and mean %BF at 3 months of corrected age (n = 25) was 20 +/– 4. Mean differences in %BF between the intervention group and the control group were not statistically significant at 36 weeks PMA (−0.8) or 3 months corrected age (−1.2). Similarly, feeding practices during hospitalization did not differ between groups. Growth outcomes did not differ between groups. Conclusions Serial assessments of body composition at birth, 36 weeks PMA, and 3 months corrected age in very preterm infants show increased %BF in both intervention and control groups without an apparent influence of the intervention on feeding practices. While 36 weeks PMA has been a common assessment point for research purposes, body composition assessments may need to be done at earlier intervals in order to make meaningful clinical changes to the infant diet in order to affect body composition later in infancy. Funding Sources UAB OHDRC.

Impact of Coronavirus Disease 2019 on Pulmonary Function in Early Convalescence Phase

Objective: This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. Methods: A prospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-minute walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. Results: 57 patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p=0.019), higher lung total severity score（TSS）and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. Conclusion: Declining DLCO, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.