Ataxia-Telangiectasia (A-T) is a rare, autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, and increased cancer risk. Mutations in the ATM gene, which is essential for DNA damage repair, underlie this condition. This study reports a novel homozygous frameshift mutation (ATM_ex20 c.3062delT, p. Val1021fs) in a Chinese family with two affected siblings. The mutation, located in exon 20, has not been previously documented, expanding the spectrum of ATM mutations. The proband and her older sister presented with classic A-T symptoms, including gait instability and conjunctival telangiectasia. Both siblings presented with immunodeficiency, characterized by low immunoglobulin A (IgA) levels, slightly elevated IgM levels, and elevated alpha-fetoprotein (AFP). Cranial magnetic resonance imaging (MRI) findings revealed cerebellar atrophy and cerebral white matter lesions in both sisters. Interestingly, while both sisters shared the same mutation, their clinical severity differed, highlighting the complexity of genotype-phenotype correlations in A-T. The parents and an unaffected sister were heterozygous carriers, consistent with autosomal recessive inheritance. This study underscores the importance of genetic testing in A-T diagnosis and provides new insights into the genetic diversity of ATM-related diseases. Further research is needed to understand the broader implications of this mutation.

Ataxia telangiectasia (AT) is a rare autosomal recessive primary immunodeficiency disorder (PID) resulting from a mutation in the ATM gene involved in DNA repair. We describe the case of a young girl with cutaneous granulomas that developed after childhood vaccinations. Immunohistochemistry revealed granulomas induced by the rubella virus vaccine. This finding raises the question of the safety of live rubella vaccine strains in immunocompromised children.

Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder characterized by immunodeficiency, progressive cerebellar ataxia, and an increased malignancy risk. Cells derived from individuals with AT show multiple defects, including high oxidant and ionizing radiation sensitivities, poor DNA repair, low iron-sulfur cluster levels, and low reduced glutathione. The clinical course of AT is progressive and unrelenting, with most individuals having a survival time of approximately twenty-five years. Presently, AT has no effective treatments, and most patients receive supportive care only. Recently, pioglitazone, a thiazolidinedione class used to treat type 2 diabetes, has been demonstrated to exert beneficial effects on AT cells and on diabetic individuals with AT. Here, I will discuss the possible molecular mechanisms of pioglitazone's favorable effects on the AT phenotype and why it may have utility in treating some aspects of AT.

Ataxia telangiectasia (AT) is a rare neurocutaneous syndrome that results from biallelic pathogenic variants in the ataxia telangiectasia mutated (ATM) gene, named for its characteristic cerebellar ataxia in the early toddler years and variable oculocutaneous telangiectasias in the school age years. While its name only hints at neurologic and cutaneous manifestations, this multisystemic disorder also has important immunologic, oncologic, respiratory, and endocrinologic implications. This article will review the function of the ATM gene, the neurologic manifestations of AT, non-neurologic complications, mimickers of AT (including other disorders of defective DNA repair), and the realm of therapeutic research for AT.

Introduction: Inborn errors of immunity (IEI) are characterized by an inherited dysregulation or absence of immune system components that can manifest clinically in complications that predispose an individual to feeding difficulties or impaired swallowing, digestion, and absorption. Treatment side-effects or altered requirements may further impair nutritional status. While adequate nutrition is necessary for optimal growth and immune function, little is known about nutritional intakes in IEI, and best practice nutrition guidelines are limited. This review aimed to synthesize current evidence on the dietary intakes, anthropometry and nutritional biochemistry in individuals with an IEI.

Methods: A systematic review of literature published from database inception to March 2023 was conducted in accordance with the PRISMA guidelines. Articles eligible for inclusion reported anthropometric, biochemical, or dietary intake-related measures in pediatric or adult patients with a diagnosed IEI. Identified articles were screened for eligibility; data was synthesized descriptively.

Results: A total of 4488 studies were retrieved of which 34 were included. Across studies, 2894 IEI individuals were included (age range 4 weeks to 83y), predominantly focusing on ataxia telangiectasia (AT) and common variable immunodeficiency (CVID). A significant association between inadequate energy intakes and IEI was identified (n=6 studies); however, there was significant variability in adequacy of macro- and micronutrients across studies. Patients with IEI were at risk of malnutrition (range 30% to 70%); although anthropometric assessment measures were not consistent across studies. Biochemical assessments found patients were also at risk of micronutrient deficiencies including vitamin D.

Discussion: This review identified few studies assessing dietary intakes, anthropometry and nutritional biochemistry in patients with IEI, with considerable heterogeneity across studies. Future longitudinal studies using consistent validated dietary assessment tools and anthropometric measures in diverse IEI patient populations are needed. This review reinforces the need for dietetic input in people with an IEI and the development evidence-based clinical practice guidelines for people with an IEI.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412365.

Ataxia telangiectasia (AT), Louis-Bar syndrome, is a rare neurodegenerative disorder caused by autosomal recessive biallelic mutations within the ataxia telangiectasia mutated (ATM) gene. Currently, there are no curative therapies available for this disorder. This review provides an overview of the latest advances in treatment methods including 1- Acetyl-DL-leucine, 2- Bone Marrow Transplantation, 3- Gene Therapy, 4- Dexamethasone, and finally 5- Red Blood Cells (RBCs) as a carrier for dexamethasone (encapsulation of dexamethasone sodium phosphate into autologous erythrocytes, known as EryDex). Most of the treatments under investigation are in the early stages, except for the EryDex System. It appears that the EryDex system and N-Acetyl-DL-Leucine may hold promise as potential treatment options.

Genomic instability disorders are characterized by DNA or chromosomal instability, resulting in various clinical manifestations, including developmental anomalies, immunodeficiency, and increased risk of developing cancers beginning in childhood. Many of these genomic instability disorders also present with exquisite sensitivity to anticancer treatments such as ionizing radiation and chemotherapy, which may further increase the risk of second cancers. In July 2023, the American Association for Cancer Research held the second Childhood Cancer Predisposition Workshop, where multidisciplinary international experts discussed, reviewed, and updated recommendations for children with cancer predisposition syndromes. This article discusses childhood cancer risks and surveillance recommendations for the group of genomic instability disorders with predominantly recessive inheritance, including the DNA repair disorders ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi anemia, xeroderma pigmentosum, Bloom syndrome, and Rothmund-Thomson syndrome, as well as the telomere biology disorders and mosaic variegated aneuploidy. Recognition of children with genomic instability disorders is important in order to make the proper diagnosis, enable genetic counseling, and inform cancer screening, cancer risk reduction, and choice of anticancer therapy.

Ataxiatelangiectasia (A-T) is an infrequent genetic neurodegenerative disorder inherited autosomal recessively. It is mainly characterized by early-onset progressive cerebellar ataxia and dilated capillaries in the oculocutaneous regions especially conjunctivae so-called telangiectasia. A-T is a multisystem disorder and requires multi-disciplinary approach to management. Diagnosis is difficult in some cases because presentation is not in the same manner and showing a phenotypic spectrum. In atypical cases serum immunoglobulins and alfa fetoprotein are normal and telangiectasia is absent. We present a 5.5-year-old boy with progressive cerebellar ataxia and history of repeated sino-pulmonary infections that was homozygote for ataxia-telangiectasia mutated gene and had a giant arachnoid cyst in left hemisphere. It is important to keep in mind those cases with ataxia and repeated sino-pulmonary infections may be ataxia telangectasia patients. Genetic study is helpful and confirms the diagnosis by showing ataxia-telangiectasia mutated gene.

Hereditary ataxia (HA) is a diverse group of rare inherited neurological disorders characterised by cerebellar impairment and the progressive degeneration of spinocerebellar tracts and the spinal cord. These conditions manifest predominantly as unsteady gait, speech difficulties, dysphagia and motor skill impairment. The complex genetic causes and varied disease mechanisms underlying HA contribute to the multi-systemic symptoms which pose challenges in developing targeted effective treatments. Currently, available options for HA primarily focus on symptomatic management, highlighting a critical need for complementary therapeutic strategies, such as dietary and lifestyle interventions. This review explains recent findings on dietary and nutraceutical interventions, as well as lifestyle modifications such as exercise and rehabilitation programs for HA. It outlines common types of HA, including Friedreich ataxia, spinocerebellar ataxias, ataxia with vitamin E deficiency, ataxia-telangiectasia, and studies on a mixed cohort of patients with HA. The current management options, therapeutic implications of findings from pre-clinical and clinical data and future directions to advance the treatment of HA will also be discussed. The integration of nutraceuticals and rehabilitation programs with current methods of symptomatic management is encouraged for the holistic treatment of HA. These interventions will complement the use of various technological aids with the support of a multidisciplinary health and medical team to improve monitoring of the health status and disease progression of affected individuals; thus facilitating early treatment and an optimised clinical outcome.