Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare central nervous system neoplasms characterized by the absence of a primary brain or spinal cord tumor. Patients exhibit common radiological and histopathological features; however, the clinical progression varies. We present the case of a 4-year-old girl initially diagnosed with constipation and failure to thrive, who subsequently developed neurological signs during hospitalization. Subsequently, she was referred with suspected tuberculosis meningitis, despite negative cerebrospinal fluid (CSF) culture results, and the patient presumably started on anti-TB and methylprednisolone. Later, magnetic resonance imaging (MRI) demonstrated diffuse nodular meningeal enhancement, suggestive of infectious, autoimmune, or neoplastic etiologies. Further histopathological examination confirmed DLGNT by identifying atypical glial cells, lymphohistiocytic infiltrate, fibrosis, and the presence of the BRAF V600E mutation. Given the rarity of the condition and its recent recognition in the World Health Organization (WHO) classification, many clinicians may be unfamiliar with DLGNT. Consequently, molecular diagnosis is essential, as exemplified in this case.

Pilocytic astrocytoma (PA) is a common paediatric brain tumour that usually presents with neurological or visual symptoms linked to its location. This report describes a seven-month-old boy with an unusual presentation marked by poor feeding, progressive weight loss, and recurrent vomiting over three months, without early neurological signs. Extensive initial assessments, including feeding evaluations, multidisciplinary reviews, and pharmacological trials, did not reveal a cause. Ultimately, neuroimaging identified a large suprasellar mass with leptomeningeal deposits. Following lumbar puncture, histopathological examination of the biopsy specimen, and molecular testing, the diagnosis of PA was confirmed. Treatment was subsequently initiated with carboplatin and vincristine. Unlike typical PA cases, which often involve headaches, visual problems, or motor deficits, this case underscores that systemic, nonspecific symptoms can signal central nervous system disease. The report highlights the importance of considering neuroimaging in infants with persistent vomiting and failure to thrive to enable earlier diagnosis and potentially improve outcomes in atypical PA presentations.

Hypoxia upregulated 1 (HYOU1) is a stress-inducible ER chaperone. We investigated 2 unrelated patients carrying biallelic HYOU1 variants and presenting with primary immunodeficiency. Patient 1, homozygous for p.Pro444His, displayed failure to thrive, hypoglycemia, B cell lymphopenia, and neutropenia. Patient 2, compound heterozygous for p.Arg262Gln and p.Pro757_Glu758insAla, exhibited recurrent infections, enteropathy, and hypogammaglobulinemia. In Patient 1, while HYOU1 transcription was preserved, the protein was severely reduced. Tunicamycin treatment of dermal fibroblasts showed a blunted unfolded protein response and defective induction of ER stress-responsive genes. Immunophenotyping showed near-absence of circulating B cells, and single-cell RNA sequencing of bone marrow identified an arrest at the pro-B cell stage. Neutrophils displayed hypogranulation and dysregulated IFN- and apoptosis-associated transcriptional signatures, unresponsive to G-CSF. HYOU1 deficiency hence results in ER stress-induced proteostasis failure that simultaneously impairs adaptive immunity through B cell developmental arrest and innate immunity through neutrophil dysfunction and IFN pathway imbalance. This work expands the spectrum of HYOU1 deficiency and further identifies ER proteostasis as a central determinant of immune homeostasis.

Major histocompatibility complex class II (MHC-II) deficiency is a rare autosomal recessive combined immunodeficiency caused by defects in transcriptional regulators controlling HLA class II expression. The disorder is more prevalent in North Africa due to high rates of consanguinity and founder effects. Updated national data remain limited (in Morocco, up-to-date national data on this deficit remain limited). We aimed to describe the epidemiological, clinical, immunological, and genetic characteristics, as well as the outcomes of Moroccan patients with MHC-II deficiency. We conducted a retrospective cross-sectional study including 54 patients diagnosed with MHC-II deficiency at the national referral center for primary immunodeficiencies in Casablanca, between January 1998 and December 2024. The diagnosis was based on the absence or marked reduction (<5%) in HLA-DR surface expression on B lymphocytes and monocytes, as demonstrated by flow cytometry, with molecular confirmation when available. Demographic, clinical, immunological, genetic, therapeutic, and outcome data were analyzed. Included patients were issued from 47 unrelated families, and parental consanguinity was reported in 87% of cases. Median age at symptom onset was 6 months and median age at diagnosis was 19 months, reflecting a diagnostic delay of 13 months. Respiratory infections were the most frequent manifestation (96%), followed by gastrointestinal involvement (68.5%), mucocutaneous infections (75.9%), and failure to thrive (96%). Autoimmune cytopenia occurred in 20.4% of patients. Immunologic evaluation showed CD4[+] T-cell lymphopenia in 86.7%, with hypogammaglobulinemia. Genetic testing (n = 35) identified the recurrent RFXANK founder deletion (c.338-25_338del26) in 97.1% of genotyped patients, while one patient carried a CIITA mutation. Hematopoietic stem cell transplantation (HSCT) was performed in eight patients (14.8%), with a survival rate of 62.5% among transplanted cases. Overall mortality reached 66.7%. MHC-II deficiency in Morocco is characterized by early onset, high consanguinity, and a strong RFXANK founder effect, but remains marked by delayed diagnosis and poor survival. Early clinical recognition, targeted molecular screening in high-risk families, improved access to HSCT, and optimized preventive strategies are critical to improve outcomes.

Hypoxia upregulated 1 (HYOU1) is a stress-inducible ER chaperone. We investigated 2 unrelated patients carrying biallelic HYOU1 variants and presenting with primary immunodeficiency. Patient 1, homozygous for p.Pro444His, displayed failure to thrive, hypoglycemia, B cell lymphopenia, and neutropenia. Patient 2, compound heterozygous for p.Arg262Gln and p.Pro757_Glu758insAla, exhibited recurrent infections, enteropathy, and hypogammaglobulinemia. In Patient 1, while HYOU1 transcription was preserved, the protein was severely reduced. Tunicamycin treatment of dermal fibroblasts showed a blunted unfolded protein response and defective induction of ER stress-responsive genes. Immunophenotyping showed near-absence of circulating B cells, and single-cell RNA sequencing of bone marrow identified an arrest at the pro-B cell stage. Neutrophils displayed hypogranulation and dysregulated IFN- and apoptosis-associated transcriptional signatures, unresponsive to G-CSF. HYOU1 deficiency hence results in ER stress-induced proteostasis failure that simultaneously impairs adaptive immunity through B cell developmental arrest and innate immunity through neutrophil dysfunction and IFN pathway imbalance. This work expands the spectrum of HYOU1 deficiency and further identifies ER proteostasis as a central determinant of immune homeostasis.