Transcobalamin deficiency is an autosomal recessive disease caused by pathogenic variants in the TCN2 gene. It is a multisystem disorder, with haematological manifestations such as megaloblastic anaemia and pancytopenia. Neurological manifestations include ataxia, hypotonia and neuropathy. Gastrointestinal and immunological clinical presentations include diarrhoea, cytomegalovirus (CMV) colitis, failure to thrive and recurrent infections.We report a female toddler who initially presented at early infancy with severe failure to thrive, diarrhoea, CMV colitis and pancytopenia and was initially diagnosed with childhood myelodysplastic syndrome based on bone marrow examination and a strong family history in her cousins. Whole exome sequencing revealed a homozygous pathogenic variant, c.927_930del (p.(Cys309Trpfs*50)), in the TCN2, consistent with a diagnosis of autosomal recessive transcobalamin deficiency. Treatment with parenteral hydroxocobalamin resulted in dramatic improvement in her symptoms and resolved the myelodysplastic changes.

CHAPLE syndrome is an ultra-rare genetic cause of protein-losing enteropathy (PLE) resulting from uncontrolled complement activation due to CD55 deficiency. We report two paediatric patients presenting with recurrent diarrhoea, hypoalbuminaemia, hypogammaglobulinaemia and growth failure, both initially evaluated as intestinal lymphangiectasia. Persistent symptoms and poor response to conventional therapy prompted genetic evaluation, which revealed pathogenic variants in the CD55 gene in both children, confirming the diagnosis of CHAPLE syndrome. Both patients required repeated albumin and intravenous immunoglobulin replacement prior to diagnosis. Targeted therapy with pozelimab was initiated. Rapid clinical and biochemical improvement was observed within 2 weeks, with sustained normalisation of albumin, total protein and immunoglobulin levels. At 3-month follow-up, both children remained in clinical remission without further need for albumin or immunoglobulin infusions. These cases highlight the importance of considering genetic causes in children with refractory PLE and demonstrate the effectiveness of early targeted complement inhibition in CHAPLE syndrome.

Atrial septal defect (ASD) is considered a benign condition and is usually closed electively in pre-school age. Early symptomatic presentation is uncommon and often associated with comorbidities such as chronic lung disease and recurrent respiratory infections. Although pulmonary hypertension is rare in ASD, infants with large defects may develop respiratory symptoms and failure to thrive even in its absence. In such conditions earlier intervention may be considered, particularly in those with right heart volume overload or growth impairment. However, limited evidence suggests potential benefit from early intervention, especially in infants with bronchopulmonary dysplasia. This study aims to systematically review the literature and perform a pooled analysis of clinical and hemodynamic characteristics of children undergoing early ASD closure (weight < 15 kg or age < 2 years). Additionally, it evaluates the safety and efficacy of both surgical and transcatheter closure in this population.

Infants presenting with microcephaly may present with misshapen head abnormalities that warrant surgical intervention or further investigation. Cranial growth restriction may occur secondary to impaired cerebral development with patent sutures, a diagnostic distinction with critical implications for management. Craniosynostosis, characterized by premature fusion of cranial sutures, is a common consideration in infants presenting with abnormal skull morphology and microcephaly. Agenesis of the corpus callosum (ACC) is a congenital brain malformation that may present with microcephaly, failure to thrive, and early developmental delay, potentially mimicking craniosynostosis on physical examination. A two-month-old male infant born at term via uncomplicated vaginal delivery presented with microcephaly, failure to thrive, and unmet developmental milestones. Based on the infant's abnormal head shape, he was suspected of having craniosynostosis. Growth parameters demonstrated severe restriction: length 2nd percentile, weight less than the 1st percentile, and head circumference less than the 1st percentile, with minimal interval growth from birth to 2 months. Physical examination revealed palpable ridging along the coronal sutures and a small, flat anterior fontanelle. Neurologic assessment demonstrated absent social smile and poor eye contact despite intact pupillary responses, full conjugate eye movements, and normal extremity movement. Feeding difficulties requiring post-prandial suctioning raised concern for laryngomalacia or another upper airway obstruction with a possible need for nasogastric tube placement. Computed tomography demonstrated no evidence of craniosynostosis. Subsequent magnetic resonance imaging revealed complex ACC with colpocephaly, parallel lateral ventricles, and a Blake pouch cyst (BPC). Pediatric neurosurgical evaluation concluded that cranial growth restriction was secondary to impaired cerebral development rather than primary suture pathology. Genetic evaluation and neurodevelopmental follow-up were initiated. This case illustrates a critical diagnostic pitfall: cranial suture ridging and microcephaly do not always indicate craniosynostosis. In infants with failure to thrive, abnormal head growth and underlying brain malformations, such as ACC, may produce secondary cranial restriction with patent sutures. The presence of congenital microcephaly and early developmental concerns, such as absent social interaction, should heighten suspicion for underlying structural brain abnormalities. Early recognition of this distinction is essential to initiate appropriate genetic evaluation and neurodevelopmental monitoring. Complex ACC with associated anomalies warrants a comprehensive workup with multidisciplinary evaluations, as outcomes depend significantly on the presence of additional malformations and underlying genetic etiology.

Vasoactive intestinal peptide (VIP)-secreting neuroblastic tumors are rare pediatric neoplasms that may present with chronic secretory diarrhea prior to tumor detection, posing significant diagnostic and therapeutic challenges. VIP-induced diarrhea is typically profuse, watery, and refractory to standard management, often resulting in dehydration, electrolyte imbalance, weight loss, and failure to thrive. Herein, we report two pediatric patients with neuroblastoma who presented with chronic secretory diarrhea as the initial and predominant symptom. In both cases, the persistent diarrhea remained unexplained by common etiologies and was unresponsive to conventional therapies. After approximately three months of ongoing symptoms accompanied by progressive abdominal distension, radiologic evaluation revealed intra-abdominal masses in both cases. The diagnosis of neuroblastoma was confirmed by tumor biopsy in one patient and bone marrow biopsy in the other. Serum VIP levels were not available in either case; however, the clinical presentation was consistent with VIP-mediated secretory diarrhea. Although surgical resection of VIP-secreting neuroblastic tumors in localized disease is typically associated with resolution of diarrhea and favorable outcomes, delayed diagnosis could result in advanced, metastatic, and inoperable disease. Both of our cases had metastatic, inoperable disease at the time of diagnosis, and proved fatal in one. These cases underscore the importance of considering VIP-secreting neuroblastic tumors in the differential diagnosis of children presenting with unexplained, treatment-resistant secretory diarrhea. Early recognition may facilitate timely diagnosis and improve clinical outcomes.

Giardia duodenalis, a member of the genus Giardia, is a common intestinal protozoan parasite in humans and some farm, companion, and wild animals. Due to the uniform morphology of the parasites sampled from a wide range of hosts, the taxonomy of the genus Giardia has been the subject of debate for more than a century. The confusion generated by this controversy, and the technological limitations to carry out the necessary research to clarify the matter, led to an insufficient understanding of the epidemiology of the infection, mainly in aspects related to host specificity and zoonotic transmission. The results of molecular and epidemiological studies conducted over the last four decades, which are reviewed in this paper, allow us to conclude that zoonotic transmission of Giardia duodenalis infection is possible. Concurrently, these findings suggest that most Giardia infections are host-specific, rendering zoonotic transmission relatively uncommon. Nevertheless, from a public health perspective, such transmission remains a critical concern for vulnerable groups, particularly children and immunocompromised individuals. In these populations, even infrequent zoonotic events can lead to severe clinical outcomes, including chronic diarrhea, malabsorption, and failure to thrive.

A 70-year-old man with progressive bronchiectatic lung disease, cirrhosis, and hepatocellular carcinoma supposedly secondary to hepatitis B was referred to our institution for further evaluation. A detailed medical history identified the patient as of Romanian Jewish ethnicity with no prior familial or genetic disease reported. As a young child, he reported hospitalization for failure to thrive but no respiratory complaints. In adulthood, he underwent a cholecystectomy for gallbladder stones and successful fertility treatment resulting in 2 children. His liver and lung diseases became clinically significant in his late 40s. Chronic productive cough and repeated episodes of hemoptysis led to a diagnosis of bilateral bronchiectasis, particularly affecting the upper and middle lobes. A few years prior, he underwent angiography and embolization of a tortuous left bronchial artery due to massive hemoptysis. The patient reported anorexia and significant weight loss of 20 kg, accompanied by intermittent diarrhea, which were attributed to his underlying lung and liver conditions.