Metabolic effects of high diet acid load (DAL) have been studied for years in adults, although only recently in children. Contemporary diets, especially those of Western societies, owe their acidogenic effect to high animal-origin protein content and low contribution of base-forming elements, such as fruits and vegetables. This imbalance, where dietary acid precursors exceed the body\'s buffering capacity, results in an acid-retaining state known by terms such as \"eubicarbonatemic metabolic acidosis,\" \"low-grade metabolic acidosis,\" \"subclinical acidosis,\" or \"acid stress\". Its consequences have been linked to chronic systemic inflammation, contributing to various noncommunicable diseases traditionally considered more common in adulthood, but now have been recognized to originate at much earlier ages. In children, effects of high DAL are not limited to growth impairment caused by alterations of bone and muscle metabolism, but also represent a risk factor for conditions such as obesity, insulin resistance, diabetes, hypertension, urolithiasis, and chronic kidney disease (CKD). The possibility that high DAL may be a cause of chronic acid-retaining states in children with growth impairment should alert pediatricians and pediatric nephrologists, since its causes have been attributed traditionally to inborn errors of metabolism and renal pathologies such as CKD and renal tubular acidosis. The interplay between DAL, overall diet quality, and its cascading effects on children\'s health necessitates comprehensive nutritional assessments and interventions. This narrative review explores the clinical relevance of diet-induced acid retention in children and highlights the potential for prevention through dietary modifications, particularly by increasing fruit and vegetable intake alongside appropriate protein consumption.

BACKGROUND: RASopathies are associated with an increased risk of autism spectrum disorder (ASD). For neurofibromatosis type 1 (NF1) there is ample evidence for this increased risk, while for other RASopathies this association has been studied less. No specific ASD profile has been delineated so far for RASopathies or a specific RASopathy individually.
METHODS: We conducted a systematic review to investigate whether a specific RASopathy is associated with a specific ASD profile, or if RASopathies altogether have a distinct ASD profile compared to idiopathic ASD (iASD). We searched PubMed, Web of Science, and Open Grey for data about ASD features in RASopathies and potential modifiers.
RESULTS: We included 41 articles on ASD features in NF1, Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Individuals with NF1, NS, CS, and CFC on average have higher ASD symptomatology than healthy controls and unaffected siblings, though less than people with iASD. There is insufficient evidence for a distinct ASD phenotype in RASopathies compared to iASD or when RASopathies are compared with each other. We identified several potentially modifying factors of ASD symptoms in RASopathies.
CONCLUSIONS: Our systematic review found no convincing evidence for a specific ASD profile in RASopathies compared to iASD, or in a specific RASopathy compared to other RASopathies. However, we identified important limitations in the research literature which may also account for this result. These limitations are discussed and recommendations for future research are formulated.

The care of infants at risk of poor growth and development is a global priority. To inform new WHO guidelines update on prevention and management of growth faltering among infants under six months, we examined the effectiveness of postnatal maternal or caregiver interventions on outcomes among infants between 0 and 6 months. We searched nine electronic databases from January 2000 to August 2021, included interventional studies, evaluated the quality of evidence for seven outcome domains (anthropometric recovery, child development, anthropometric outcomes, mortality, readmission, relapse, and non-response) and followed the GRADE approach for certainty of evidence. We identified thirteen studies with preterm and/or low birth weight infants assessing effects of breastfeeding counselling or education (n = 8), maternal nutrition supplementation (n = 2), mental health (n = 1), relaxation therapy (n = 1), and cash transfer (n = 1) interventions. The evidence from these studies had serious indirectness and high risk of bias. Evidence suggests breastfeeding counselling or education compared to standard care may increase infant weight at one month, weight at two months and length at one month; however, the evidence is very uncertain (very low quality). Maternal nutrition supplementation compared to standard care may not increase infant weight at 36 weeks postmenstrual age and may not reduce infant mortality by 36 weeks post-menstrual age (low quality). Evidence on the effectiveness of postnatal maternal or caregiver interventions on outcomes among infants under six months with growth faltering is limited and of \'low\' to \'very low\' quality. This emphasizes the urgent need for future research. The protocol was registered with PROSPERO (CRD42022309001).

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS.
We searched the WangFang and China National Knowledge Infrastructure databases with the keywords \"Shwachman-Diamond syndrome,\" \"SDS,\" \"SBDS gene\" and \"inherited bone marrow failure\" for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using \"Shwachman-diamond syndrome\" as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included.
The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years.
Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention.

TRPM6 is predominantly expressed in the kidney and colon and encodes a protein containing an ion channel domain and a protein kinase domain. It is crucial for magnesium homeostasis and plays important roles in epithelial magnesium transport and the active magnesium absorption. In this study, we present a 70-day-old Iranian female patient from consanguineous parents with hypomagnesemia and secondary hypocalcemia. She presented with seizures 19 days after birth and refractory watery non-bloody diarrhea. She consequently had failure to thrive. Other features included hypotonia, wide anterior fontanel, ventriculomegaly, and pseudotumor cerebri following administration of nalidixic acid. She had severe hypomagnesemia and hypocalcemia which were treated with magnesium and calcium supplementation. Despite initial unstable response to supplemental magnesium, she eventually improved and the diarrhea discontinued. The patient was discharged by magnesium and calcium therapy. At the last follow-up at age 2.5 years, the patient remained well without any recurrence or complication. Genetic testing by whole-exome sequencing revealed a novel homozygous frameshift insertion-deletion (indel) variant in exon 26 of the TRPM6 gene, c.3693-3699del GCAAGAG ins CTGCTGTTGACATCTGCT, p.L1231Ffs*36. Segregation analysis revealed the TRPM6 heterozygous variant in both parents. Patients with biallelic TRPM6 pathogenic variants typically exhibit hypomagnesemia with secondary hypocalcemia and present with neurologic manifestations including seizures. In some patients, this is also complicated by chronic diarrhea and failure to thrive. Long-term complications are rare and most of the patients show a good prognosis with supplemental magnesium therapy.

BACKGROUND: Older adults have a higher visit rate and poorer health outcomes in the emergency department (ED) compared to their younger counterparts. Older adults are more likely to require additional resources and hospital admission. The nonspecific, atypical, and complex nature of disease presentation in older adults challenges current ED triage systems. Acute illness in older adults is often missed or commonly disguised in the ED as a social or functional issue. If diagnostic clarity is lacking or safe discharge from the ED is not feasible, then older adults may be labelled a \"social admission\" (or another synonymous term), often leading to negative health consequences.
OBJECTIVE: This scoping review aims to describe and synthesize the available evidence on patient characteristics, adverse events, and health outcomes for older adults labelled as \"social admission\" (and other synonymously used terms), as well as those with nonacute or nonspecific complaints in the ED or hospital setting.
METHODS: A literature search of MEDLINE, Embase, Scopus, PsycINFO, and CINAHL was completed. Relevant reference lists were screened. Data have been managed using EndNote software and the Covidence web application. Original data have been included if patients are aged ≥65 years and are considered a \"social admission\" (or other synonymously used term) or if they present to the ED with a nonacute or nonspecific complaint. Two review team members have reviewed titles and abstracts and will review full-text articles. Disagreements are resolved by consensus or in discussion with a third reviewer. This review does not require research ethics approval.
RESULTS: As of January 2023, we have completed the title and abstract screening and have started the full-text screening. Some remaining full-text articles are being retrieved and/or translated. We are extracting data from included studies. Data will be presented in a narrative and descriptive manner, summarizing key concepts, patient characteristics, and health outcomes of patients labelled as a \"social admission\" (and other synonymously used terms) and of those with nonacute and nonspecific complaints. We expect the first results for publication in Spring 2023.
CONCLUSIONS: Acute illness in the older adult is not always easily identified. We hope to better understand patient characteristics, adverse events, and health outcomes of older adults labelled as a \"social admission,\" as well as those with nonacute or nonspecific complaints. We aim to identify priorities for future research and identify knowledge gaps that may inform health care providers caring for these vulnerable patients.
UNASSIGNED: DERR1-10.2196/38246.

Russel described a rare clinical entity known as diencephalic syndrome (DS) in 1951, which was traditionally caused by a neoplasm in the hypothalamic-optic chiasmatic region. DS is characterized by severe emaciation despite adequate or slightly reduced caloric intake, locomotor hyperactivity, euphoria and other minor features. Current evidence suggests that a rare population of children with a similar phenotype may have their tumor located in the posterior fossa instead, defining the DS-like presentation, a rare entity with few cases reported in the literature.
A thorough search of three databases (PubMed, Ovid Medline, and Ovid Embase) was conducted to identify relevant papers reporting children with DS associated with brainstem tumors. To our knowledge, only seven cases have been documented in the literature. Moreover, we present four of our own cases, focusing on the unusual clinical presentation, the diagnosis process, and the lag time between the initial symptoms and the definitive diagnosis.
In this review, the mean lag time between the onset of symptoms and diagnosis was 20.9 months (median: 16 months; range: 1.5-72 months), whereas in our series of cases, the time was 32.5 months (median: 33 months; range: 7-57 months).
Despite recent significant advances in neuro-oncology diagnostic tools, this mean lag time did not improve when compared with the previous literature review from 1976. Throughout these data, we aim to raise awareness in the hopes of detecting intracranial neoplasms earlier in cases of children with profound emaciation of unknown cause.

Hereditary actin-related protein 2/3 complex subunit 1B deficiency is characterized clinically by ear, skin, and lung infections, bleeding, eczema, food allergy, asthma, skin vasculitis, colitis, arthritis, short stature, and lymphadenopathy.
We aimed to describe the clinical, laboratory, and genetic features of six patients from four Mexican families.
We performed exome sequencing in patients of four families with suspected actinopathy, collected their data from medical records, and reviewed the literature for reports of other patients with actin-related protein 2/3 complex subunit 1B deficiency.
Six patients from four families were included. All had recurrent infections, mainly bacterial pneumonia, and cellulitis. A total of 67% had eczema whereas 50% had food allergies, failure to thrive, hepatomegaly, and bleeding. Eosinophilia was found in all; 84% had thrombocytopenia, 67% had abnormal-size platelets and anemia. Serum levels of IgG, IgA, and IgE were highly increased in most; IgM was normal or low. T cells were decreased in 67% of patients, whereas B and NK cells were increased in half of patients. Two of the four probands had compound heterozygous variants. One patient was successfully transplanted. We identified 28 other patients whose most prevalent features were eczema, recurrent infections, failure to thrive, bleeding, diarrhea, allergies, vasculitis, eosinophilia, platelet abnormalities, high IgE/IgA, low T cells, and high B cells.
Actin-related protein 2/3 complex subunit 1B deficiency has a variable and heterogeneous clinical spectrum, expanded by these cases to include keloid scars and Epstein-Barr virus chronic hepatitis. A novel deletion in exon 8 was shared by three unrelated families and might be the result of a founder effect.

The aim of our study was to better define the clinical pattern of diencephalic syndrome, a rare but potentially lethal cause of failure to thrive in infancy. Poor weight gain or weight loss, the characteristic presenting feature, often firstly attributed to gastrointestinal or endocrinological or genetic diseases, is secondary to a malfunctioning hypothalamus, caused by a diencephalic tumor. Due to its unexpected clinical onset, diagnostic delay and misdiagnosis are common. We described a case series of 3 children with diencephalic syndrome admitted at our Hospital, over a 5-year period. Furthermore, a narrative review on all pediatric cases published in the last seventy years was performed. Clinical pattern, timing to diagnosis, neuroimaging, management, and outcome were analyzed. Our three cases are singularly described in all clinical and diagnostic findings. Overall, 100 children were selected; all these cases as well as our children presented with failure to thrive: 96% had body mass index or weight-length/height ratio lower than 5th percentile. Vomiting and hyperactivity are reported in 35 and 26% of cases, respectively. The neurological features, mainly nystagmus reported in 43%, may occur late in the disease course. In conclusion, the diagnostic delay is the hallmark of diencephalic syndrome, confirming the lack of knowledge by clinicians. The poor weight gain/loss despite adequate length growth and food intake, especially in children with hyperactivity and good psychomotor development, should alert pediatricians towards this condition, before neurological signs/symptoms occurrence.

BACKGROUND: Menke-Hennekam syndrome (MHS) is a rare and recently described syndrome consecutive to the variants in exon 30 or 31 in CREBBP (CREB-binding protein gene). The CREB-binding protein (CREBBP) and EP300 genes are two commonly expressed genes whose products possess acetyltransferase activity for histones and various other proteins. Mutations that affect these two genes are known to cause Rubinstein-Taybi syndrome (RTS); however, with the application of whole exome sequencing (WES) there were reports of variants that affect specific regions of exon 30 or 31 of these two genes but without the specific phenotype of RTS.
METHODS: A review of the available literature was conducted, aimed at underscoring the difficulties in diagnosing MHS based on phenotype particularities.
RESULTS: Five applicable studies were identified by searching PubMed, Web of Science, and Scopus databases for publications up to November 2021 using the key terms \"Menke-Hennekam syndrome\" and \"CREBBP\".
CONCLUSIONS: In this paper, we present a new case and highlight the importance of exome sequencing to identify different mutations of exons 30 and 31 of the CREBBP gene involved in MHS, and we make formal recommendations based on our literature review.