Alström Syndrome: A Review Focusing on Its Diverse Clinical Manifestations and Their Etiology as a Ciliopathy.

Alström syndrome is a form of inherited obesity caused by a single gene abnormality and is inherited as an autosomal recessive trait. It is characterised by a variety of clinical manifestations, including progressive visual and hearing impairment, type 2 diabetes mellitus, dilated cardiomyopathy, and hepatic and renal dysfunction, in addition to obesity. Recent insights underline the pivotal involvement of the disease-associated gene (ALMS1) in cilia formation and function, leading to the classification of its clinical manifestations as a ciliopathy. This review delineates the diverse clinical indicators defining the syndrome and elucidates its pathological underpinnings.

Switching to burosumab from conventional therapy in siblings with relatively well-controlled X-linked hypophosphatemia.

Burosumab, a fully human monoclonal antibody against fibroblast growth factor 23, is mainly administered to patients with severe X-linked hypophosphatemia (XLH). However, there have been few reports on its use in relatively mild cases. In this report, we administered burosumab to two siblings with XLH who had been effectively treated with oral phosphate and active vitamin D. Both patients showed further improvement in radiographic and laboratory findings with burosumab compared with conventional treatment. Upon switching treatment, popliteal pain was reported in case 1 until her phosphorus levels normalized. This emphasizes the importance of monitoring not only rickets and calcium/phosphate metabolism but all symptoms of XLH after initiating burosumab. Notably, in cases 1 and 2, burosumab sustained catch-up growth, especially in case 1, who had not yet reached puberty. Further clinical studies are needed to determine whether burosumab improves growth and proportional abnormalities in patients with mild XLH.

Bystanders' Willingness to Perform Basic Life Support and Its Relationship with Facilitative and Obstructive Factors: A Nationwide Survey in Japan.

Background: The administration of basic life support (BLS) by bystanders is essential to improve the survival rates of patients who have experienced out-of-hospital cardiac arrest (OHCA). Although providing BLS to individuals who experience OHCA greatly improves their chances of survival, the actual implementation rate is low. Therefore, we investigated the association between bystanders' willingness to perform BLS and facilitative/obstructive factors with the objective of identifying educational methods that would improve the likelihood of bystanders performing BLS should they encounter a patient with OHCA. Methods: The study participants included 502 male and 498 female Japanese residents (total, 1000 participants) with no experience in performing BLS and 42 male and 59 female Japanese residents (total 101 participants) with experience in performing BLS. The participants were aged 15-65 years. Both groups graded the strength of their willingness to perform BLS in the future on a 4-point scale, as well as their level of agreement with factors facilitating or obstructing their willingness to perform BLS. These factors were established based on the theory of helping behavior, which defines psychological states when helping others in social psychology.We then analyzed the associations between willingness to perform BLS in the future and their level of agreement with factors facilitating or obstructing their willingness to perform BLS. Results: The willingness to perform BLS decreased in accordance with the increase in the level of intervention required for patients who experienced OHCA , and was significantly associated with four facilitating factors: sufficient ability and experience to perform BLS, personal advantage, high personal norms, and psychological closeness to the patient. Conclusion: Our results suggested that workshops and other educational activities focused on these facilitative factors may be helpful in increasing the rate at which bystanders perform BLS.

Factors Related to Young People's Willingness to Perform Basic Life Support.

Background: Survival rates increase when basic life support (BLS) is provided by bystanders to patients with acute diseases, such as out-of-hospital cardiac arrest; however, its implementation rate is not high. In this study, we investigated "interest on BLS," "knowledge on BLS," and "experience on BLS" as factors related to the willingness to implement BLS among junior high school, high school, and college students who have multiple opportunities to learn it. Methods: This is an observational study using a questionnaire survey. The participants were 112 junior high school students, 114 high school students, and 109 university students (non-medical), totaling 294 (87.8% response rate). The questionnaire listed three items on the strength of willingness to perform BLS, three items on attributes of the participant, four items on the score of interest on BLS, one item on the score of knowledge on BLS, and two items on the score of experience on BLS. Results: Among junior high school students, the factors that were significantly associated with the willingness to perform BLS were "Presence of someone who died" and "Interest on BLS" score. Among high school and college students, the factors that were significantly associated with the willingness to perform BLS were "Interest on BLS" and "Knowledge on BLS" scores. Conclusion: For junior high school students, creating an environment in which they can visualize the actual situation may increase their interest, whereas for high school and university students, in addition to such an environment, conducting seminars of short duration may help them to consolidate their knowledge and increase their willingness to implement BLS.

Cognitive and Emotional Changes in Peer Educators of Type 2 Diabetes Patients After Starting Peer-Support Activities.

Background: Diabetes self-management education through peer support has beneficial effects, especially in regions with limited medical resources. To ensure peer educators continue to provide peer-led education programs, it is important that they remain motivated to instruct patients. Here, to explore measures to enhance peer-educators' motivation toward such programs, we examined the cognitive and emotional changes in Filipino type 2 diabetics after 7-month activities as peer educators. Methods: We individually performed semi-structured interviews with 13 peer educators with 20 years of age or above in August 2017 (immediately before starting their peer-education activities) and in March 2018 (7 months after the start). The first interview was performed after the peer educators had received 2-day training of diabetes self-management. In both interviews, we asked the peer educators about their feelings toward peer-led educational activities (e.g., satisfaction, difficulty, reward, confidence, and challenges). Their replies about their own cognition and emotions were interpreted and integrated, and then analyzed qualitatively. Results: Four and seven categories were extracted from the first and second interviews, respectively. The category "Cognition of patients' active learning attitudes and of positive changes in patients' physical conditions and behavior" observed in the second interview led to "Cognition of growth as a peer educator" and "Satisfaction with supporting patients as a peer educator." These two feelings gave the peer educators' "Increased motivation to continue the activities as a peer educator." This motivation was also associated with "Active collaboration among peer educators," which was affected by "Difficulties and concerns in working as a peer educator." Conclusion: To sustain diabetic peer-led education programs, we suggest that interventions be implemented that increase peer educators' motivation toward their activities and stimulate their awareness of the importance of collaborating with one another. Such collaboration should help to overcome the difficulties they may face in providing peer-led education.

The process by which mothers of children with special healthcare needs evolve their connections with the community.

Mothers of children with special healthcare needs often face many extra difficulties, such as being isolated in the community. This study, conducted in the San'in region of Japan between December 2017 and February 2019, aimed to clarify how the mothers established and adapted their connections within their communities through a qualitative descriptive design study. Participants were 12 mothers caring for children with special healthcare needs. Verbatim data on adapting to life after hospital discharge was collected through interviews and analyzed by the modified grounded theory approach. The data generated 14 concepts, which were grouped into four categories, as follows: Difficulties in life that arise from caring for children in social isolation; gaining an objective view of the current situation and future of caring for children with special healthcare needs; collaboration based on the understanding of relationships with others; and feeling fulfilled in life. These describe four phases that the mothers went through which are similar to each stage of the transition theory. Providing support via a collaborative partnership may be effective for mothers experiencing anxiety during the transition stages.

Genotype-Structure-Phenotype Correlations of Disease-Associated IGF1R Variants and Similarities to Those of INSR Variants.

We previously reported genotype-phenotype correlations in 12 missense variants causing severe insulin resistance, located in the second and third fibronectin type III (FnIII) domains of the insulin receptor (INSR), containing the α-ß cleavage and part of insulin-binding sites. This study aimed to identify genotype-phenotype correlations in FnIII domain variants of IGF1R, a structurally related homolog of INSR, which may be associated with growth retardation, using the recently reported crystal structures of IGF1R. A structural bioinformatics analysis of five previously reported disease-associated heterozygous missense variants and a likely benign variant in the FnIII domains of IGF1R predicted that the disease-associated variants would severely impair the hydrophobic core formation and stability of the FnIII domains or affect the α-ß cleavage site, while the likely benign variant would not affect the folding of the domains. A functional analysis of these variants in CHO cells showed impaired receptor processing and autophosphorylation in cells expressing the disease-associated variants but not in those expressing the wild-type form or the likely benign variant. These results demonstrated genotype-phenotype correlations in the FnIII domain variants of IGF1R, which are presumably consistent with those of INSR and would help in the early diagnosis of patients with disease-associated IGF1R variants.

Effects of a Self-efficacy Theory-Based Training Program for Peers of Patients with Type 2 Diabetes.

BACKGROUND: Training peer leaders to deliver patient education is expected to be a low-cost approach to providing healthcare in urban-poor areas affected by a shortage of healthcare professionals. The purpose of this study was to examine the effects of a training program on the self-efficacy and knowledge of peer leaders with type 2 diabetes. METHODS: A single-group longitudinal survey with baseline, intervention, and follow-up periods was conducted at a diabetes clinic in a small municipality in Metro Manila, Philippines. The intervention, a self-efficacy theory-based training program for peer-leaders of diabetic patients conducted in August 2017, comprised hands-on learning, demonstrations, quizzes, role-playing, group sharing, physical exercise, and a buffet lunch. The primary outcome was participants' self-efficacy for management of their diabetes. Secondary outcomes were participants' knowledge of diabetes and levels of emotional distress, motivation, and confidence for guiding their peers, satisfaction with the training program, hemoglobin A1c, and quality of life. RESULTS: At 12 and 18 months after the intervention, participants' knowledge of diabetes was significantly increased compared with baseline (both P < 0.05). At earlier time points, an increasing, but not significant, trend was observed. The change in knowledge of diabetes from baseline to 18 months after intervention tended to be positively correlated with the change in self-efficacy (r = 0.594, P = 0.054). No significant differences were observed for any of the other outcomes, although the descriptive statistics showed an increasing trend for all of the outcomes except motivation. CONCLUSION: The training program significantly improved participants' knowledge of diabetes at 12 and 18 months after the training programs compared with baseline. A positive correlation between the changes in the levels of knowledge and self-efficacy suggested that the observed improvement of self-efficacy was facilitated by the improvement of knowledge of diabetes.

A Randomized Placebo-controlled Trial of an Oral Preparation of High Molecular Weight Fucoidan in Patients with Type 2 Diabetes with Evaluation of Taste Sensitivity.

BACKGROUND: Fucoidan is derived from seaweed widely used in Japanese cuisine, but little is known about its influence on glucose metabolism. To obtain information about the physiological effects of fucoidan on glucose metabolism, the digestive system, and the gustatory system controlling taste sensation in patients with type 2 diabetes, we conducted a randomized, double-blind, placebo-controlled study. METHODS: Thirty patients with type 2 diabetes on diet therapy were recruited from an outpatient clinic (22 men and 8 women aged 59.10 ± 13.24 years, body mass index: 25.18 ± 3.88, hemoglobin A1c: 7.04 ± 1.24%). They were divided into 2 groups and underwent 2 interventions with a 4-week interval. One group received fucoidan for 12 weeks (a daily 60 mL test beverage containing 1,620 mg of fucoidan) and then placebo (60 mL) for the subsequent 12-week period, while the order was reversed in the other group. Evaluation was performed just before and after each intervention. Taste sensitivity was measured for 5 basic tastes by the filter paper disk method and food intake was evaluated with a validated diet questionnaire. RESULTS: No adverse events occurred during the study period. Despite no change of the diet, stool frequency increased during fucoidan intake (from 7.78 ± 4.64/week in Week 1 to 9.15 ± 5.03/week in Week 5, P < 0.001), and it increased more in lean subjects. In 11 subjects whose stool frequency exceeded the mean value, the thresholds for sweet, salty, bitter and umami tastes were significantly reduced (enhancement of sensitivity) after fucoidan intake. In 14 subjects with normal HOMA-IR (homeostatic model assessment of insulin resistance, < 2.5), hemoglobin A1c decreased after fucoidan intake (from 6.73 ± 1.00 to 6.59 ± 1.00%, P < 0.05), as did the fasting plasma level of GLP-1 (glucagon-like peptide-1, from 6.42 ± 3.52 to 4.93 ± 1.88 pmol/L, P < 0.05). CONCLUSION: Sustained fucoidan intake led to alterations of gastrointestinal function, including increased stool frequency and enhanced taste sensitivity, which could contribute to better control of diabetes.

A Conceptual Model for Quality of Life Among People with Type 2 Diabetes in the Philippines.

BACKGROUND: The increased prevalence of chronic diseases is a social issue in developing countries. METHODS: To create a conceptual model representing the quality of life of low-income people with type 2 diabetes in the Philippines, 117 low-income adult participants in a public support group were studied, and the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores on quality of life (QOL) were analyzed in terms of their relationships with the following factors: basic attributes, physical factors (glycated hemoglobin level, complications, comorbidities, and symptoms), social factors (support, education, and financial status), and cognitive factors (knowledge, attitude, self-efficacy, and self-management behavior). RESULTS: Based on correlation coefficients among variables and goodness-of-fit test results through a path analysis, 2 models representing causal relationships were created, both of which showed sufficient goodness-of-fit. CONCLUSION: Glycated hemoglobin levels, knowledge of blood glucose levels, self-efficacy, and self-management behavior (exercise) influenced PCS scores, while age, glycated hemoglobin levels, neuropathy, knowledge of insulin, self-efficacy, and self-management behavior (exercise) influenced MCS scores. The influence of self-efficacy was prominent in both cases, providing an important insight for healthcare professionals to develop effective support methods.

Impact of Hands-on Experience of a Cadaver Dissection on the Professional Identity Formation of Health Sciences Students.

BACKGROUND: In Japan, some nursing and health science universities that train nurses and/or clinical laboratory technicians have a curriculum in which students observe medical students performing a cadaver dissection. Observing a cadaver dissection is believed to affect the formation of a student's professional identity. This study aimed to investigate the effects of observing a cadaver dissection on the professional identity of nursing and clinical laboratory science students to find an effective educational support system for developing professional identity. METHODS: Sophomores majoring in nursing science or clinical laboratory science were asked to complete a questionnaire with a professional identity scale before and after hands-on experience of a cadaver dissection performed by medical students. After their hands-on session was complete, they responded to a free-answer question about acquiring a professional identity. RESULTS: The professional identity score of nursing students significantly decreased after the hands-on experience of the cadaver dissection. No significant change in professional identity score was observed in the clinical laboratory science students. However, the effect size (r) was moderate. CONCLUSION: Although professional identity formation fluctuates immediately after the experience of the hands-on experience of a cadaver dissection, the findings do suggest that these hands-on sessions will be effective for developing their professional identity if educational support is provided to help them utilize what they learned through reflection.

Childhood dietary intake: Comparison between anorexia nervosa and healthy leanness.

BACKGROUND: The number of adolescent patients with anorexia nervosa is increasing. In addition, an increase in pre-adolescent patients with premenarchal onset has also been recognized. Detection of the disease in childhood and adolescence, however, is not always easy because the symptoms are not characteristic during this period. This study was performed to investigate detection of anorexia nervosa in children/adolescents by comparing energy and nutrient intake between patients with anorexia nervosa and healthy thin persons. METHODS: The subjects consisted of 13 girls aged 14.4 ± 3.5 years with anorexia nervosa and 320 healthy girls aged 12.4 ± 1.3 years. Dietary intake was evaluated using a validated diet history questionnaire designed for children/adolescents. Daily energy and nutrient intake were expressed as a percentage of the age- and sex-matched reference amount. RESULTS: Healthy lean (body mass index [BMI], <50th percentile) girls with an above-average score for desiring thinness had higher fat and lower cereal intake, and a trend of lower carbohydrate intake. In contrast, patients with anorexia nervosa, compared with thin (BMI <5th percentile) girls, characteristically had significantly lower energy, fat, zinc, vitamin C, and confectionery intake. CONCLUSIONS: Lean girls with an above-average desire for thinness appear to restrict their energy intake by reducing their intake of carbohydrates such as cereals while maintaining a relatively high fat intake. In contrast, girls with anorexia nervosa avoided fat and had a preference for vegetables. This characteristic eating pattern could be a useful clue for detection of anorexia nervosa in thin children and adolescents.

Qualitative Analysis of the Psychosocial Adaptation Process in Children with Chronic Kidney Disease: Toward Effective Support During Transition from Childhood to Adulthood.

BACKGROUND: Pediatric chronic renal disease only shows abnormal values in a urinalysis in the initial stage, and subjective signs and symptoms are rare. If adolescents with chronic renal disease face a disease crisis combined with the usual developmental crisis, this may cause psychosocial maladaptation. We analyzed psychosocial adaptation in Japanese children with chronic renal disease in order to identify factors influencing healthy adaptation. METHODS: Ten children and adult patients with chronic kidney disease attending Tottori University Hospital, Japan in 2016 participated in a semi-structured interview (a modified version of the grounded theory approach) comprising questions about episodes since disease onset and thoughts/feelings at onset. RESULTS: Twenty-four concepts extracted from the data were sorted into 5 categories. These concepts and categories were expanded on an orthogonal axis with time and self-esteem in order to establish an adaptation model for children with chronic kidney disease. Category names are as follows. (Cat. 1: Emotional impact on being informed of disease, Cat. 2: Social challenges of treatment and resulting identity diffusion, Cat. 3: Emotional conflict on school return, Cat. 4: Resilience and related factors, Cat. 5: Re-establishment of identity). CONCLUSION: Since pediatric chronic renal disease has few manifestations, it is difficult for patients to accept. Children facing a chronic disease crisis plus adolescent developmental crisis may show identity diffusion. In order for children to re-establish their identity and adapt to society, factors supporting resilience are important. Key factors include school life, interactions with friends, counseling by adult mentors and family acceptance. Healthcare professionals need to provide age-appropriate information on renal disease and support patients.

Increased IRS2 mRNA Expression in SGA Neonates: PCR Analysis of Insulin/IGF Signaling in Cord Blood.

CONTEXT: Hypoglycemia is the most common metabolic problem among small-for-gestational-age (SGA) neonates. However, the pathological mechanism and insulin/ insulin-like growth factor (IGF) signaling axis in neonates remain unknown. OBJECTIVE: To determine the insulin/IGF axis in neonates, we analyzed the messenger RNA (mRNA) expression of insulin/IGF signaling in fetal umbilical cord blood. SETTING: The Perinatal Medical Center of Tottori University Hospital. PARTICIPANTS: Fifty-two [42 appropriate-for-gestational-age (AGA) and 10 SGA] neonates. INTERVENTIONS: Immediately collected cord blood was placed into a PAXgene Blood RNA Tube. Total RNA from the blood was purified using reagents provided in the PAXgene Blood RNA Kit within 4 days, and reverse transcription polymerase chain reaction (PCR) was performed. MAIN OUTCOME MEASURE: Quantitative real-time PCR analysis was applied to evaluate the mRNA expression of insulin receptor (INSR), IGF-I receptor (IGF1R), insulin receptor substrate 1 (IRS1), IRS2, and glucose transporters (SLC2A2 and SLC2A4). ß-Actin was used as a control gene. RESULTS: Serum glucose and IGF-I levels in SGA neonates were significantly lower. The cord serum insulin levels were similar between AGA and SGA neonates. The IRS2 mRNA expression was significantly higher in SGA than in AGA neonates (P < 0.05). The IRS2 mRNA expression was significantly higher in hypoglycemic SGA neonates than in normoglycemic SGA neonates. CONCLUSIONS: We determined that intrauterine growth restriction induces increased IRS2 mRNA expression in cord blood, without hyperinsulinemia. The increased expression of IRS2 mRNA might be associated with abnormal glucose metabolism in SGA neonates. Our findings might lead to the elucidation of abnormal glucose metabolism in SGA neonates.

A novel frameshift mutation in NR3C2 leads to decreased expression of mineralocorticoid receptor: a family with renal pseudohypoaldosteronism type 1.

Pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disease characterized by resistance to aldosterone, and the renal form of PHA1 is associated with heterozygous inactivating mutations in NR3C2, which encodes mineralocorticoid receptor (MR). Here we report a case of renal PHA1 due to a novel frameshift mutation in NR3C2. A 10-day-old Japanese male infant, born at 39 weeks gestation (birth weight, 2,946 g), was admitted to our hospital because of lethargy and vomiting, with a 6.7% weight loss since birth. Laboratory test results were: Na+, 132 mEq/L; K+, 6.6 mEq/L; Cl+, 93 mEq/L. Both plasma aldosterone level and plasma renin activity were markedly elevated at diagnosis, 2,940 ng/dL (normal range: 26.9-75.8 ng/dL) and 560 ng/mL/h (normal range 3.66-12.05 ng/mL/h), respectively. Direct sequence analysis of NR3C2 revealed a novel heterozygous mutation (c.3252delC) in the patient and his father. The mutation causes a frameshift starting at amino acid I 963 within the C terminal ligand-binding domain of MR and results in a putative abnormal stop codon at amino acid 994, with an extension of 10 amino acids compared to normal MR. We performed cell culture experiments to determine the levels of mutant NR3C2 mRNA and MR, and evaluate the effects of the mutation on MR response to aldosterone. The mutation decreased the expression of MR, but not NR3C2 mRNA, and led to decreased MR function, with no dominant negative effect. These results provide important information about MR function and NR3C2 mutation in PHA1.

Current Status of the Utilization of Powered Wheelchair in Preschool Children with Locomotive Disability in Japan.

[Purpose] This study aimed to elucidate the actual state of powered wheelchair (PWC) prescription for preschool children with disabilities in Japan, and also to determine the approximate number of preschool children with disabilities who would potentially benefit from PWC use. [Subjects and Methods] A total of 318 facilities providing rehabilitation for disabled children in Japan were enrolled in the study. A questionnaire about PWC use for preschoolers was mailed to the facilities. Each study items were analyzed employing the Fisher's exact test. [Results] Of the 318 facilities, consent to participate in this study was obtained from 108 (return rate: 34.0%). After PWC provision, many facilities reported improvement in quality of life indices for preschool children with disabilities. It was revealed that there were 6 preschool children from 2 to 6 years of age with disabilities who might acquire a means of independent locomotion through PWC provision and thereby experience improved quality of life. [Conclusion] There was no negative comment from the facilities studied about the prescription and provision of PWC for preschool children with disabilities.

Seating arrangements for children with insufficient head control: lessons from trials using the i2i head & neck positioning & support system.

[Purpose] An insufficient head control is the most troublesome condition for children with impaired mobility who require optimal seating. [Subjects and Methods] We report on the clinical trial of the newly developed i2i head & neck positioning & support system called i2i for locomotively disabled children with periventricular leukomalacia (PVL). [Results] Two major advantages of the i2i were observed in the trial. The first was its favorable effect on the alignment of the spine to prevent scoliosis and to provide stable breathing and optimal seating, which resulted in improvement of the children's activities of daily living (ADL). The second was its direct application of force to the head rather than indirectly to the pelvis in a conventional seat arrangement. The conventional way of head support is based on stabilization of the trunk which is based on stabilization of the pelvis by some seating arrangement. [Conclusion] The trial of the i2i device demonstrated its usefulness in helping PVL children with insufficient head control develop their abilities while preventing secondary disability.

Heterozygous nonsense mutations near the C-terminal region of IGF1R in two patients with small-for-gestational-age-related short stature.

OBJECTIVE: The type I insulin-like growth factor I receptor (IGF1R) plays an important role in growth. We aimed to evaluate the detailed mechanism underlying the effect of IGF1R on human growth. PATIENTS AND METHODS: We have performed sequence analysis of IGF1R in 55 patients with SGA short stature in Japan, since 2004, and identified novel heterozygous nonsense mutations in 2 patients: an 8-year-old Japanese boy (case 1), with a birthweight of 2228 g (-3·3 SDS) and height of 46 cm (-2·1 SDS), and a 3-year-old Japanese girl (case 2), with a birthweight of 2110 g (-3·0 SDS) and height of 44·3 cm (-2·8 SDS). Both patients had a short stature (-3·2 SDS, -3·1 SDS). We determined the protein expression of mutated IGF1R, assessed the effect of the endoplasmic reticulum-associated degradation (ERAD) pathway on mutated IGF1R, assessed the dominant-negative effect of IGF1R and performed quantitative RT-PCR analysis of IGF1R mRNA expression in whole blood cells. RESULTS: Two novel heterozygous nonsense mutations (case 1: p.Q1250X and case 2: p.W1249X) were identified. Although these mutations did not affect blood IGF1R mRNA levels, they significantly decreased the expression of IGF1R protein in transiently transfected cells. Treatment with the proteasome inhibitor MG132 showed significantly increased IGF1R protein. CONCLUSIONS: Heterozygous nonsense mutations affecting the C-terminal region (p.Q1250X, p.W1249X) of IGF1R decreased the expression of IGF1R through the ERAD pathway. Our study revealed the importance of the C-terminal region and the dosage of this receptor for growth.

A rare CYP 21 mutation (p.E431K) induced deactivation of CYP 21A2 and resulted in congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is caused by mutations in the CYP21A2 gene. The residual enzyme activity is strongly associated with the phenotype. We describe a rare case of CAH with a rare CYP21A2 mutation. The patient was a one-year-old Japanese boy. At 16 days old, he was referred to our hospital because of elevated serum 17-OH-progesterone (17-OHP) levels in neonatal screening. The compound heterozygous mutations (IVS2-13 A/C>G, and p.E431K) in CYP21A2 were identified at 2 months old, and we diagnosed non-classical CAH, since he did not have significant physical signs (pigmentation and salt-wasting). However, his body weight decreased, and his serum 17-OHP level (99.5 ng/mL) was elevated at 3 months old. Steroid replacement therapy was started at 3 months old. Our patient's clinical course resembled simple virilizing (SV) CAH, but classification was difficult because the patient showed increased renin activity indicating an aldosterone deficiency, and late onset of symptoms. While the IVS 2-13 A/C>G mutation is common in the classical form of CAH, p.E431K is a rare point mutation. Functional analysis revealed that the residual enzyme activity of p.E431L was 5.08±2.55% for 17-OHP and 4.12±2.37% for progesterone, which is consistent with SV CAH. p.E431 is localized in the L-helix near the heme-binding site. The mutation might interfere with heme binding, leading to deactivation of CYP21A2. This report showed that CYP21A2 p.E431 has an important effect on enzyme activity.

Psychosocial profiles of children with achondroplasia in terms of their short stature-related stress: a nationwide survey in Japan.

AIMS AND OBJECTIVES: To assess psychosocial profiles of children with achondroplasia using a nationwide survey. BACKGROUND: Achondroplasia, showing short stature and disproportionately short limbs, causes physical inconvenience such as difficulty in reaching high objects. It is, however, still controversial whether the condition is associated with psychological problems, especially in childhood. DESIGN: A cross-sectional descriptive design was employed. METHODS: To evaluate psychosocial profiles and adaptation processes in children with achondroplasia, we developed an inventory of scales based on the psychological stress model of which conceptual framework was comprised of stressor, coping process, coping resource and adaptation outcome domains. Participants were recruited nationwide through the largest advocacy support group for achondroplasia in Japan. Of the 130 group members, 73 X-ray-diagnosed patients, aged 8-18 years, completed the inventory of questionnaires to be analysed. RESULTS: As for the stressor domain, patients experienced short stature-related unpleasant experiences more frequently (z-score: +1·3 in average, +3·9 in physical inconvenience). Nevertheless, these experiences had little effect on the coping process (threat appraisal: -0·2, control appraisal: +0·1) and the adaptation outcome (stress response: +0·3, self-concept: 0·0). Interestingly, self-efficacy in the coping resource domain was noticeably increased (+3·1) and was strongly correlated with most variables in the coping process and in adaptation outcome domains. CONCLUSIONS: Although the children with achondroplasia experienced more short stature-related stressors, there was no evidence of any psychosocial maladaptation. This finding suggests that coping process as well as coping resources such as self-efficacy could be important targets for promoting psychological adjustment in children with achondroplasia. RELEVANCE TO CLINICAL PRACTICE: To help children with achondroplasia adapt socially, nurses and other healthcare providers should routinely assess their psychological adaptation process, especially cognitive appraisal and self-efficacy.