Evidence suggests that ARV1 regulates sterol movement within the cell. Saccharomyces cerevisiae cells lacking ScArv1 have defects in sterol trafficking, distribution, and biosynthesis. HepG2 cells treated with hARV1 antisense oligonucleotides accumulate cholesterol in the endoplasmic reticulum. Mice lacking Arv1 have a lean phenotype when fed a high fat diet and show no signs of liver triglyceride or cholesterol accumulation, suggesting a role for Arv1 in lipid transport. Here, we explored the direct lipid-binding activity of recombinant human ARV1 using in vitro lipid-binding assays. ARV1 lipid-binding activity was observed within the first N-terminal 98 amino acids containing the conserved ARV1 homology domain (AHD). The zinc-binding domain and conserved cysteine clusters within the AHD were necessary for lipid binding. Both full-length ARV1 and the AHD bound cholesterol, several phospholipids, and phosphoinositides with high affinity. The AHD showed the highest binding affinity for monophosphorylated phosphoinositides. Several conserved amino acids within the AHD were necessary for phospholipid binding. Biochemical studies suggested that ARV1 exists as a dimer in cells, with oligomerization being critical for ARV1 function, as amino acid mutations predicted to have a negative effect on dimerization caused weakened or complete loss of lipid binding. Our results show for the first time that human ARV1 can directly bind cholesterol and phospholipids. How this activity may function to regulate lipid binding and maintain proper lipid trafficking and/or transport in cells requires further studies.

Achalasia, a rare esophageal disorder with an annual incidence of 0.11 per 100,000 in children, is characterized by impaired lower esophageal sphincter (LES) relaxation and peristalsis. Infantile cases are extremely uncommon and often linked to genetic conditions like Allgrove and Down syndrome. Diagnosis is challenging due to overlapping symptoms with other pediatric conditions, relying on barium esophagography and esophageal manometry. Heller myotomy remains the preferred surgical treatment to reduce LES pressure.

A 3-month-old female presented with a history of cough, feeding difficulties, and regurgitation, accompanied by respiratory distress and recurrent pneumonia. She was diagnosed with achalasia cardia based on clinical findings and contrast-enhanced esophagography. A modified Heller myotomy with Dor-fundoplication was performed successfully, with no postoperative complications. The patient was discharged in stable condition.

Infantile achalasia, a rare condition with unclear etiology, often presents diagnostic challenges. Our early-onset case, lacking syndromic associations, was complicated by recurrent pneumonia, necessitating surgical intervention. The successful outcome after a modified Heller myotomy with Dor-fundoplication supports its efficacy in severe pediatric cases, though long-term monitoring for recurrence is essential.

Achalasia cardia, though rare in infants, should be considered as differential in cases of recurrent pneumonia and feeding difficulties, as its presentation often mimics more common conditions. Prompt diagnosis through thorough evaluation and imaging is essential to ensure timely treatment and improve outcomes.

Triple-A syndrome (Triple-A) is an autosomal recessive disorder characterized by alacrimia, achalasia, and adrenal insufficiency. Several variants on the AAAS gene have been described, and some variants are clustered in particular geographical areas, such as the c.1331+1G>A variant which is very frequent in North Africa. Here, we describe the genetic features of Triple-A in a series of unrelated families from Morocco.

Screening for the AAAS c.1331+1G>A variant was performed by direct sequencing or by PCR-RFLP. Haplotype analysis using Single Tandem Repeat (STR) markers flanking AAAS gene was performed in order to evaluate the founder effect and estimate the age of the c.1331+1G>A variant.

Seven unrelated families with ten individuals clinically diagnosed with Triple-A were evaluated for sequence variations in the AAAS gene. The median age at diagnosis was 3 years, with a range between 2 and 11 years. Molecular analysis revealed that all patients were homozygous for the c.1331+1G>A variant. This variant was not found in 200 healthy controls, indicating that carriers are very rare in the general Moroccan population. Subsequently, STR marker analysis revealed a founder effect and that the most recent common ancestor of Triple-A patients in Morocco would have lived 125 years ago.

This is the largest series of Triple-A in Morocco. The same AAAS c.1331+1G>A variant was found in all patients, suggesting a founder effect in Morocco which was subsequently confirmed by microsatellite marker analysis. Therefore, this variant should be systematically investigated to diagnose Triple-A in Morocco.

Achalasia cardia, type of esophageal dynamic disorder, is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sphincter. Loss of function of the distal and lower esophageal sphincter ganglion cells is the main cause of achalasia cardia, and is more likely to occur in the elderly. Histological changes in the esophageal mucosa are considered pathogenic; however, studies have found that inflammation and genetic changes at the molecular level may also cause achalasia cardia, resulting in dysphagia, reflux, aspiration, retrosternal pain, and weight loss. Currently, the treatment options for achalasia focus on reducing the resting pressure of the lower esophageal sphincter, helping to empty the esophagus and relieve symptoms. Treatment measures include botulinum toxin injection, inflatable dilation, stent insertion, and surgical myotomy (open or laparoscopic). Surgical procedures are often subject to controversy owing to concerns about safety and effectiveness, particularly in older patients. Herein, we review clinical epidemiological and experimental data to determine the prevalence, pathogenesis, clinical presentation, diagnostic criteria, and treatment options for achalasia to support its clinical management.