22q11.２欠失症候群

The combined newborn screening program for Spinal Muscular Atrophy (SMA) and Severe Combined Immunodeficiency (SCID) was evaluated in Liguria through a five-year pilot study involving 32,289 newborns. A single multiplex real-time PCR assay on dried blood spots enabled simultaneous detection of SMN1 exon 7 deletions and quantification of T-Cell Receptor Excision Circles (TREC) and Kappa-Deleting Recombination Excision Circles (KREC), achieving near-complete population coverage and a low recall rate. Ten newborns received a confirmed diagnosis of a targeted condition: five newborns were diagnosed with spinal muscular atrophy (SMA), of whom four were treated presymptomatically and achieved favorable clinical outcomes, whereas one with SMA type 0 died a few days after birth. Five newborns were diagnosed with immunodeficiencies, including two cases of adenosine deaminase (ADA)-related severe combined immunodeficiency (SCID), and three clinically significant secondary findings (idiopathic T-cell lymphopenia, DiGeorge syndrome, and transient B-cell lymphopenia). No false-negative cases were observed during follow-up. The TREC and KREC profiles were consistent with the underlying immunological diagnoses. Overall, the study demonstrates that combined SMA and SCID newborn screening is feasible, reliable, and clinically impactful, supporting its integration into public health screening programs.

BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a multisystem genetic disorder associated with a significantly increased risk of early-onset Parkinson's disease (EOPD). Management is challenging because psychiatric and cognitive comorbidities often limit advanced therapies such as deep brain stimulation (DBS). CASES: We report 2 patients with 22q11DS who developed EOPD at about age 30 with prominent psychiatric manifestations. In both cases, diagnosis of 22q11DS was delayed until genetic testing was performed for atypical parkinsonism associated with intellectual disability and dysmorphic features. Severe motor fluctuations and dyskinesia developed early. Because of psychiatric vulnerability, DBS and dopamine agonists were considered unsuitable. Continuous intrajejunal levodopa-carbidopa infusion (LCIG [levodopa-carbidopa intestinal gel]) was initiated, which led to sustained improvement in motor fluctuations and functional status, although individualized dose adjustments were required. CONCLUSIONS: LCIG may represent a valuable therapeutic option in selected patients with 22q11DS-associated Parkinson's disease when psychiatric comorbidity limits other advanced therapies.

BACKGROUND: TANGO2 deficiency disorder is an ultra-rare autosomal recessive condition characterized by life-threatening metabolic crises with rhabdomyolysis and cardiac arrhythmias. Patients with 22q11.2 deletion syndrome are at increased risk when a pathogenic variant occurs in the remaining allele, yet this dual diagnosis remains underrecognized as clinicians often attribute all manifestations to the primary genetic condition. We report a case of a child with confirmed 22q11.2 deletion syndrome in whom a coexisting variant in the TANGO2 gene was diagnosed at the age of 5 after first metabolic crisis with rhabdomyolysis. CASE PRESENTATION: A girl with 22q11.2 deletion syndrome diagnosed in infancy exhibited global developmental delay and chronic excessive sleepiness attributed to her established diagnosis. At age 5, she experienced her first metabolic crisis during pneumonia with severe rhabdomyolysis (creatine kinase >100,000 U/L), features inconsistent with isolated 22q11.2 deletion syndrome. Two additional metabolic crises occurred at age 7 before exome sequencing revealed a hemizygous TANGO2 variant c.536G>A, confirming TANGO2 deficiency. A previously unreported hemizygous missense variant c.536G>A (p.Gly138Glu) in the TANGO2 gene (NM_152906.7) was identified and verified by NGS-based deep amplicon sequencing and Sanger direct sequencing; segregation analysis confirmed paternal inheritance with the maternal allele deleted within the 22q11.2 region. Following diagnosis, B-vitamin supplementation, coenzyme Q10, L-carnitine, and gastrostomy tube placement were initiated to ensure consistent hydration and prevent prolonged periods without nutrition, a known crisis trigger. The patient achieved 4 years of crisis-free stability with reduced daytime sleepiness. At age 11, she remains stable without further crises. CONCLUSIONS: This case demonstrates that exome sequencing should be pursued early when atypical features emerge in patients with established genetic diagnoses. The sustained crisis-free period following gastrostomy placement supports proactive nutritional intervention in TANGO2 patients with feeding difficulties. Clinicians must recognize that microdeletion syndrome patients can harbor variants unmasking additional autosomal recessive conditions requiring distinct management.

OBJECTIVE: Pediatric nontuberculous mycobacterial (NTM) infections are frequently misdiagnosed due to their heterogeneous clinical presentations, which can mimic pulmonary tuberculosis, common respiratory diseases, or other infectious conditions depending on the site of involvement. This case series aimed to characterize the host susceptibility spectrum underlying pediatric NTM infection across both pulmonary and extrapulmonary sites, with emphasis on the diagnostic role of targeted next-generation sequencing (tNGS). METHODS: We conducted a retrospective analysis of five pediatric patients with confirmed NTM infection diagnosed at Fujian Provincial Fuzhou Pulmonary Hospital between January and December 2025. Clinical characteristics, predisposing factors, therapeutic regimens, and clinical outcomes were systematically reviewed and discussed in the context of relevant literature. RESULTS: The cohort included 5 children aged 7 months to 12 years. Pathogenic species were Mycobacterium abscessus (n = 4) and Mycobacterium paragordonae (n = 1). Infection sites included the lungs (n = 3), cervical lymph nodes (n = 1), and parotid gland (n = 1). Predisposing factors ranged from localized infection in immunocompetent children to congenital airway anomalies, DiGeorge syndrome, and cystic fibrosis with bronchiectasis. All patients improved after individualized multidrug therapy and were discharged. CONCLUSIONS: Pediatric NTM infection is associated with a broad spectrum of predisposing factors, including bronchiectasis, cystic fibrosis, congenital airway anomalies, and systemic immunodeficiency such as DiGeorge syndrome. tNGS demonstrated significant diagnostic value in identifying NTM species and should be considered when conventional methods are insufficient.