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A complex group of inherited disorders of lipid metabolism resulting in systemic deposition of triglycerides and, to a lesser extent, cholesterol.

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TSD type I

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TSD type II

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TSD type III: Wolman Disease; Lysosomal Acid Lipase Deficiency; Acid Cholesteryl Ester Hydrolase Deficiency, Wolman type; Cholesteryl Ester Storage Disease.

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TSD with Impaired Long Chain Fatty Acid Oxydation: Ichthyotic Neutral Lipid Storage Disease; Dorfman-Chanarin Syndrome; Chanarin-Dorfman Syndrome.

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TSD type I, unknown. TSD type II, autosomal dominant. TSD type III (Wolman disease), autosomal recessive. TSD with impaired long-chain fatty acid oxidation, autosomal recessive.

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Normal mobilization of lipids from peripheral tissues requires catecholamine-induced activation of adenyl-cyclase and cAMP, which activate protein kinase. Activated protein kinase, in turn, activates triglyceride lipase, releasing free fatty acids and glycerol from the cell. In type I TSD, a defect of the adenyl-cyclase or catecholamine receptor is postulated. In type II TSD, abnormality of protein kinase is proposed. In type III TSD, a defect of the triglyceride lipase is proposed. Lipogenesis appears normal in all these conditions. The inability or impaired ability to mobilize lipids results in widespread lipid deposition. Classification into myocardial and skin types has been suggested to reflect the predominant tissues of triglyceride deposition, although it is important to note that TSD is a multisystem disorder.

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Clinical history and examination. Laboratory findings include vacuolated granulocytes (Jordan anomaly) and histological evidence of excess triglyceride in adipose tissue. In vitro study of response of tissue adenyl-cyclase to catecholamines may be undertaken.

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The presentation is variable between and within the subtypes of TSD. Type I TSD presents with failure to thrive and emaciation and type II presents with obesity. Type II TSD patients are able to mobilize lipids independently of the hormone-sensitive lipase pathway. Type III TSD (Wolman Disease) presents in the neonatal period and carries a poor prognosis (death by age 6 months), although less-aggressive forms of type III TSD are described. Signs and symptoms can include cutaneous lipid deposition, ichthyosis, vomiting, diarrhea, steatorrhea, malabsorption, portal hypertension, hepatosplenomegaly, adrenal calcification, and widespread xanthomata. Central nervous system involvement can include developmental delay (especially type III TSD), ptosis, cataracts, nystagmus, ataxia, areflexia, and cranial nerve palsies. Muscle infiltration results in a skeletal myopathy, and cardiac involvement results in a dilated cardiomyopathy. Cardiomyopathy was a common finding in one Japanese cohort. Pulmonary hypertension has been described in one patient with type III TSD. Treatment includes lipid-lowering drugs and careful control of lipid intake.

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Careful clinical examination for clinical signs of impaired cardiorespiratory reserve, examine for evidence of muscle hypotonia. Cardiovascular assessment. Twelve-lead ECG must be obtained to exclude conduction abnormalities; low threshold for echocardiography must be performed to exclude dilated cardiomyopathy. Chest radiography is indicated if ventricular failure is suspected. Laboratory investigations: check electrolytes and renal function and correct any abnormalities; full blood count; liver function tests including coagulation studies. Consider possibility ...

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