Citrin deficiency (CD) is a rare autosomal recessive metabolic disorder caused by pathogenic variants in the SLC25A13 gene, which encodes the mitochondrial aspartate-glutamate carrier 2, also known as citrin. We describe an 11-year-old Chinese boy presenting with recurrent acute pancreatitis secondary to severe hypertriglyceridemia during the FTTDCD/post-NICCD stage of citrin deficiency. The patient was relatively thin (his height and weight were at the 10th percentile on the growth curve for Chinese children), had a strong preference for soy products and an aversion to carbohydrates. Laboratory tests at presentation revealed severe hypertriglyceridemia (28.96 mmol/L), with a previously documented peak of 30.35 mmol/L. Abdominal computed tomography showed diffuse pancreatic enlargement and peripancreatic inflammatory changes, which, together with compatible abdominal pain, supported the diagnosis of acute pancreatitis. Genetic sequencing identified compound heterozygous pathogenic mutations in the SLC25A13 gene (exon 9: c.852_855delTATG; intron 6: c.615+5G > A). Plasma ammonia and citrulline levels were within normal limits. All of these findings supported a diagnosis of failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD) in the post-NICCD phase. Management involved plasma exchange, a high-protein/high-fat/low-carbohydrate diet, and medium-chain triglyceride (MCT) supplementation, leading to clinical improvement. However, poor dietary adherence during follow-up resulted in two readmissions for recurrent pancreatitis. This case highlights that citrin deficiency should be considered in children with recurrent acute pancreatitis associated with severe hypertriglyceridemia, especially when accompanied by carbohydrate aversion and unusual dietary preferences, even in the absence of hyperammonemia or hypercitrullinemia.

ACOX1-sEDD is an ultrarare neurocutaneous disorder caused by gain-of-function variants in ACOX1, leading to excessive oxidative activity and multisystem injury. We report a male infant who, from the second week of life, developed a generalized erythematous desquamative greasy eruption with sparse dysplastic ocher-colored scalp hair, followed by recurrent bilateral corneal epithelial defects, progressive hypotonia, failure to thrive, and seizures with diffuse symmetric leukoencephalopathy on brain MRI. Metabolic testing showed elevated dicarboxylic acids and medium-/long-chain acylcarnitines despite normal very-long-chain fatty acids and classical peroxisomal biomarkers, and trio exome sequencing identified de novo ACOX1 c.710A>G (p.Asn237Ser) and ROBO1 c.572delG (p.Cys191fs) variants. Cutaneous disease resolved with topical 10% N-acetylcysteine and emollients, in conjunction with oral N-acetylcysteine and adjunctive antioxidant vitamin therapy, while ocular involvement improved with vitamin A ointment and autologous serum eyedrops, supporting early recognition of ACOX1-sEDD in infants with inflammatory ichthyosiform dermatitis and ocular-neurologic involvement and suggesting that additional neurodevelopmental variants may modify disease expression.

Alveolar capillary dysplasia with misaligned pulmonary veins (ACDMPV) is one of the major causes of neonatal interstitial lung disease, causing persistent pulmonary hypertension (PH) of the newborn, although symptoms can present later in infancy. Two patients were recently diagnosed with ACD at our Institution and prompted us to perform a structured review of the condition.

Cystic developmental malformations of the oral cavity are exceedingly rare. These lesions may be identified prenatally through imaging or become apparent after birth. Clinically, these lesions manifest as a midline oral mass, often associated with feeding difficulties, airway obstruction, or failure to thrive. A 16-day-old male neonate was brought by his parents with a progressively enlarging swelling on the ventral surface of the tongue. Initially small, it soon led to poor feeding and episodes of respiratory distress, causing significant parental anxiety. Magnetic resonance imaging was suggestive of a lymphangioma. Surgical excision was performed. Histopathological examination showed cyst wall lined by respiratory pseudostratified ciliated epithelium and gastric foveolar epithelium, consistent with a foregut duplication cyst. Postoperative recovery was smooth, and the infant was able to feed comfortably. Child was followed up every 6 months and no recurrence was noted. Foregut duplication cyst involving the tongue, though rare, should be considered in the differential diagnosis of neonatal oral masses, given their potential for airway compromise.

RASopathies are a group of developmental disorders caused by variations in genes of the RAS/mitogen activated protein kinase (MAPK) pathway and affect 1 in 1000 individuals worldwide. Due to overlapping clinical features, accurate diagnosis is challenging and therefore we used next-generation sequencing (NGS) panels as an effective molecular diagnostic tool. Targeted sequencing was performed on 130 samples using a multigene panel comprising of 21 RASopathy genes. Molecular analysis revealed variations in 74 individuals (57%). Pathogenic or likely pathogenic variations were observed in 60/74 (81%) of the cases, 13 (17.5%) had variant(s) of uncertain significance (VUS), and one novel variant was identified in RASA2 whose pathogenicity has not yet been established. In individuals with Noonan Syndrome, pathogenic variants were identified in eight different genes mainly PTPN11, SOS1, RAF1 and LZTR1. Nine clinically diagnosed Cardio-facio-cutaneous syndrome cases harboured variations in BRAF, MAP2K2 and MAP2K1 The c.34G>A variant in HRAS was seen in all nine individuals diagnosed with Costello syndrome. This study provides a comprehensive molecular and clinical profile of the largest Indian RASopathy cohort. The use of targeted gene panel has increased the variation detection rate in affected individuals.

Cystic fibrosis (CF) is a progressive, autosomal recessive disease primarily affecting the pulmonary and gastrointestinal systems of afflicted individuals. Cystic fibrosis transmembrane receptor (CFTR) genes encode the CFTR protein, which allows chloride ions to pass from inside the cell to the outside of the cell. CF symptoms, such as thick, sticky mucous, result from CFTR gene dysfunction. Although many mutations in the CFTR gene have been identified, there remains an absence of a comprehensive database encompassing all known and potential mutations contributing to the pathogenesis of CF. We present a 12-year-old male with recurrent sino-pulmonary infections, asthma exacerbations, and failure to thrive. Despite a negative newborn screening test, CF was suspected. The sweat chloride test is considered the gold standard for confirming CF. This patient's sweat chloride test showed elevated levels of 63 and 66 mmol/L, respectively. Levels >60 mmol/L are considered consistent with CF. CF genotyping, however, did not uncover a known CFTR mutation. The purpose of this case report is to highlight the importance of the sweat chloride test in diagnosing CF in the setting of a negative newborn screen and the absence of a known CFTR mutation, to enhance the diagnosis and recognition of CF in pediatric patients, and to ultimately improve patient outcomes.

Arrhythmias in childhood are often challenging to diagnose and treat for a pediatrician. Tachyarrhythmias may or may not be associated with underlying structural heart disease or ion channel defects, and may also occur in the post-operative setting. Symptoms vary from excessive crying, irritability and failure to thrive, to palpitations, heart failure and syncope. Knowledge of the normal 12 lead ECG (electrocardiogram) in various stages of life and its transition to adulthood is essential in order to distinguish abnormal ECG from normal variants. Management in acute settings as well as long term medical management and interventional therapies are important. Both, cardiologists as well as pediatricians should be well-versed in the diagnosis and management of tachyarrhythmias in children.