The application of clinical genetics
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Idiopathic pulmonary fibrosis (IPF) is a group of common and lethal forms of idiopathic interstitial pulmonary disease. IPF is characterized by a progressive decline in lung function with a median survival of 2-3 years after diagnosis. Although the pathogenesis of the disease remains unknown, genetic predisposition could play a causal role in IPF. ⋯ Genome-wide association studies and whole-genome sequencing continue to reveal the genetic loci associated with IPF risk. In this review, we describe candidate genes on the basis of their functions and aim to gain a better understanding of the genetic basis of IPF. The discovered candidate genes may help to clarify pivotal aspects in the diagnosis, prognosis, and therapies of IPF.
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Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a fatal clinical disorder characterized by extracellular deposition of abnormal fibrils derived from misfolded, normally soluble transthyretin (TTR) molecules. The disease is most commonly caused by a point mutation within the TTR gene inherited in an autosomal dominant fashion. Over 100 of such mutations have been identified, leading to destabilization of the physiological TTR tetramer. ⋯ Recently, orally administered tafamidis meglumine has been approved by European authorities for treatment of FAP. The substance has been shown to stabilize the TTR tetramer, thereby improving the outcome of patients with TTR-FAP. Various other strategies have been studied in vitro to prevent TTR amyloidosis, including gene therapy, immunization, dissolution of TTR aggregates, and free radical scavengers, but none of them is ready for clinical use so far.
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Acute hyperammonemia is a medical emergency requiring rapid recognition and treatment to prevent devastating neurologic sequelae. Its varying etiologies include primary hepatic failure, drug toxicity, infection, and inherited disorders of metabolism. ⋯ Early recognition and management of metabolic encephalopathy is crucial to avoid neurologic damage, and may require hemodialysis for rapid removal of ammonia, with adjunctive medications and dietary modifications to decrease endogenous nitrogen production and activate alternate pathways of nitrogen excretion. We present the case of an adult patient with partial OTC deficiency who presented with encephalopathy, coma, and seizures, accompanied by hyperammonemia and treated acutely with hemodialysis.