The Medical clinics of North America
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Med. Clin. North Am. · Jan 2024
ReviewAttaining Diagnostic Excellence: How the Structure and Function of a Rare Disease Service Contribute to Ending the Diagnostic Odyssey.
Patients with rare or otherwise undiagnosed disorders frequently find themselves on a diagnostic odyssey, the often-prolonged journey toward diagnosis that can be characterized by significant physical, emotional, and financial hardship, as well as by diagnostic errors and delays. The wider availability of clinical exome sequencing has helped end many diagnostic odysseys, though diagnostic success rates of around 35% for exome sequencing leave many patients undiagnosed. ⋯ Diagnostic centers of excellence can improve outcomes for patients on a diagnostic odyssey by providing a process and environment that address shortfalls in diagnostic access while providing high-quality phenotyping. Features of successful undiagnosed and rare disease evaluation teams are discussed and an illustrative case is provided.
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Med. Clin. North Am. · Jan 2024
ReviewHemophagocytic Lymphohistiocytosis in Adolescents and Young Adults: Genetic Predisposition and Secondary Disease.
Hemophagocytic lymphohistiocytosis (HLH) is a disorder of impaired immune regulation resulting in hyperinflammation that is ultimately fatal if not treated. HLH is categorized into familial disease, caused by genetic mutations affecting the function of cytotoxic T lymphocytes and natural killer cells, and secondary disease, triggered by infections, malignancies, rheumatologic disorders, or immune deficiency. Adolescent and young adults with HLH represent a unique population with specific diagnostic challenges. Here we review the diagnostic criteria, possible etiologies, pathophysiology, and management of HLH with focus on the adolescent population.
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Heart failure in adolescents can manifest due to a multitude of causes. Presentation is often quite variable ranging from asymptomatic to decompensated heart failure or sudden cardiac death. ⋯ Identifying and addressing reversible pathologies often leads to functional cardiac recovery. Some disease states are irreversible and progressive, requiring chronic heart failure management and potentially advanced therapies such as transplantation.
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Common variable immunodeficiency (CVID) is the most common primary immune deficiency characterized by impaired production of specific immunoglobulin. The clinical manifestations are heterogeneous including acquisition of recurrent bacterial infections after a period of wellness, lymphoproliferation, autoimmunity, pulmonary disease, liver disease, enteropathy, granulomas, and an increased risk of malignancy. The etiology of CVID is largely unknown, with a considerable number of patients having an underlying genetic defect causing immune dysregulation. The antibody deficiency found in CVID is treated with lifelong immunoglobulin therapy, which is preventative of the majority of infections when given regularly.
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Pediatric adolescent muscle weakness can be from a variety of causes. Methodical diagnostic evaluation can lead to the category of diseases whereby phenotypic overlap requires either specialized care or broad testing patterns. However, having the ultimate diagnosis is important for prognostication.