Nabais Sá-de Vries syndrome (NSDVS) is a rare disease caused by a heterozygous mutation in the SPOP gene (17q21), which is involved in protein degradation via the ubiquitin-proteasome pathway. Different germline variants within this gene cause two distinct phenotypes (allelic heterogeneity) that affect multiple organs and systems (pleiotropy). These variants are clinically associated with intellectual disability, neurological disorders, and dysmorphic features that exhibit variable expressivity. Here, we present the case of a five-year-old girl who was conceived through assisted reproductive technology. She is the second twin of a dichorionic dizygotic pregnancy. A medical genetic evaluation was initiated at one week of age due to congenital heart disease. She presents with a fronto-parieto-occipital hemangioma, downslanting palpebral fissures, synophrys, retroauricular pits, a depressed nasal bridge, anteverted nares, midface retrusion, a high palate, a micrognathia, an inguinal hernia, bilateral single transverse palmar creases, and a congenital melanocytic nevus. She currently has delayed neurodevelopment and language acquisition, as well as microcephaly, low weight and height, and normal hearing. Exome sequencing revealed a heterozygous missense variant: NM_001007228.2(SPOP):c.351G>T(p.Met117Ile). In silicotesting classifies this variant as likely pathogenic with protein gain of function, which confirms the diagnosis of NSDVS type 1. This case report of a Mexican girl contributes to the expansion of the phenotypic spectrum of NSDVS and supports the implementation of improved multidisciplinary follow-up for affected patients.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease of the esophagus with substantial clinical manifestations including dysphagia, odynophagia, food impaction and failure to thrive in children. New evidence is emerging regarding phenotypic and symptom variations in diverse EoE populations. EoE pathogenesis involves impaired epithelial barrier function, antigen-driven Type 2 inflammation, and eosinophilic infiltration, yet eosinophil and mast cell depletion does not improve patient symptoms. Recent research has unveiled new potential mechanisms of epithelial dysfunction, including the role of epithelial alarmins in inducing downstream inflammatory cascades. New clinical scoring tools are emerging to improve diagnosis and monitor disease severity. Therapeutic approaches for EoE are rapidly evolving with a wider range of therapies becoming available. Dietary elimination, topical corticosteroids, proton pump inhibitors (PPIs), and anti-type 2 biological agents aim to provide histologic and symptomatic relief. Overall, this review aims to present recent advances in the epidemiology, pathophysiology, diagnosis, and treatment of EoE, while also extending this information to the broader field of eosinophilic gastrointestinal diseases (EGIDs).

Congenital diarrheas and enteropathies (CODE) are rare inherited disorders characterized by early-onset intractable diarrhea. Though progress has been made in elucidating the genetic basis of CODE, much remains to be discovered. Another challenge is the lack of curative therapies-treatment is primarily supportive including enteral and parenteral nutrition, and at times, intestinal transplant. We report a 3-year-old with intractable diarrhea and failure to thrive in infancy. Whole exome sequencing revealed uniparental disomy in chromosome 16. Whole genome sequencing later identified a novel point mutation in PERCC1 (proline and glutamate-rich protein with a coiled coil domain 1), a previously unannotated reading frame flanking the regulatory sequence of the "intestine-critical region", linked to enteroendocrine cell function and congenital enteropathy. Despite interventions to ameliorate malabsorption, the patient was dependent on partial parenteral nutrition secondary to profuse osmotic diarrhea, for two consecutive years. He was weaned off parenteral nutrition after starting teduglutide.

Congenital bile acid synthesis defects (BASD), the most common of which is 3β-hydroxy-Δ5-C27-steroid dehydrogenase oxidoreductase (3β-HSD7) deficiency, are a rare cause of fat-soluble vitamin malabsorption. We describe a 14-year-old girl who presented at 14 months with a left distal femur fracture and failure to thrive. It was not until 13 years of age that after several hospitalizations for bleeding and severe vitamin K deficiency, the patient was ultimately diagnosed with 3β-HSD7 deficiency. We also describe the case of an adolescent girl who was referred for treatment of Hepatitis C (HCV) and diagnosed with 3β-HSD7 deficiency after she failed to respond to therapy as expected. Finally, we review the diagnosis of BASD and highlight the challenges involved in our clinical cases. These cases demonstrate the importance of maintaining a broad differential when evaluating any patient with unexplained fat-soluble vitamin deficiencies and represent unique presentations of 3β-HSD7 deficiency in adolescent patients.

Among congenital diarrhea and enteropathies (CODEs), proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency is a rare monogenic disorder, associated with severe neonatal diarrhea and polyendocrinopathies. We report an 18-day-old male neonate, born to consanguineous parents, presenting with persistent watery diarrhea, metabolic acidosis, and failure to thrive. Genetic analysis identified a novel homozygous c.709+1 G > A splicing mutation in PCSK1, predicted to disrupt protein function. Rapid genetic diagnosis enabled timely endocrine assessment and guided nutritional management, minimizing invasive procedures. Expanding the PCSK1 mutational spectrum, this case highlights the pivotal role of next-generation sequencing in neonates with refractory diarrhea and suggestive clinical history, facilitating early intervention and improved outcomes.

The study of animal communications, termed zoosemiotics, includes the sub-field of bioacoustics, the study of the production, transmission, and reception of animal sounds. It is becoming increasingly apparent that inter- and intra-species communication is sophisticated with sound playing a major role in this signaling. Artificial intelligence-led research can be employed to understand and combine recorded multi-level data (sound, vision, odors) to classify animal health and identify interventions, also determining critical time-points for intervention. This can include subgroup discovery and trajectory analysis as essential elements in developing animal specific identification of failure to thrive or ill health. It is important that animals, carers, and veterinarians receive as early a diagnosis as possible to predict trajectory and plan care needs and interventions. However, the use of quantitative data for evidence-led interventions based on sound have not yet been developed. Here we look at advances in bioacoustics and provide a framework to determine where early diagnosis and animal health improvements can be made via understanding of behavior and oral sound production.

Mitochondrial DNA depletion syndrome (MTDPS) is a group of severe mitochondrial disorders caused by nuclear gene variants that affect mitochondrial DNA (mtDNA) replication and nucleotide synthesis. Deoxyguanosine kinase deficiency is one of the most common subtypes, typically presenting with liver dysfunction in infancy and having a poor prognosis. We report a case of MTDPS presenting with cholestasis and mild hyperlactatemia in the neonatal period, which complicated early diagnosis. Histopathological and genetic analyses established the diagnosis. The patient, a female born at 36 weeks and 1 day of gestation, weighing 2124 g, developed cholestasis, poor feeding, and failure to thrive. Hyperlactatemia was not evident at presentation but gradually increased during the clinical course. Based on suspected mitochondrial disease, mitochondrial cocktail therapy was initiated on day 64. Liver transplantation was not feasible owing to cardiac and neurological complications, and conservative treatment was continued. However, the patient died of multiple organ failure on day 89. Postmortem liver biopsy showed a markedly reduced mtDNA copy number (8.1% of control), and genetic testing revealed a homozygous c.609_610del (p.Tyr204fs) variant in the DGUOK gene (NM_080916.3), confirming the diagnosis of DGUOK-related MTDPS. This case highlights that hyperlactatemia may be absent or only mild in the early stages of MTDPS, making timely diagnosis challenging. Mitochondrial functional analysis and genetic testing should be considered early in infants with unexplained cholestasis and liver failure, regardless of the lactate levels.