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At a glance

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

Synonyms

Wolman Disease; Lysosomal Acid Lipase Deficiency; Acid Cholesteryl Ester Hydrolase Deficiency, Wolman Type; Cholesteryl Ester Storage Disease; Ichthyotic Neutral Lipid Storage Disease; Dorfman-Chanarin Syndrome; Chanarin-Dorfman Syndrome.

History

Chanarin-Dorfman Syndrome was first described in 1974 in Jerusalem. Since, more than 128 patients have been reported worldwide, especially in the Mediterranean and Middle East area.

Incidence

Extremely rare. Prevalence less than 1:1,000,000.

Classification

Three types of Triglyceride Storage Disease (TSD) are recognized:

  • TSD Type I: A paradoxical combination of triglyceride storage in peripheral adipose tissue and gross emaciation.

  • TSD Type II: Beta-adrenergic receptors, adenyl cyclase, and cyclic AMP are normally present in tissues. However, under beta stimulation, cyclic AMP does not activate triglyceride-lipase and produce glycerol.

  • TSD Type III (Wolman Disease; Lysosomal Acid Lipase Deficiency; Acid Cholesteryl Ester Hydrolase Deficiency, Wolman Type; Cholesteryl Ester Storage Disease): This medical condition also includes the TSD with impaired Long Chain Fatty Acid, also known as Ichthyotic Neutral Lipid Storage Disease; Dorfman-Chanarin Syndrome; and Chanarin-Dorfman Syndrome.

Genetic inheritance

TSD Type I, unknown. TSD Type II, autosomal dominant. TSD Type III (Wolman Disease), autosomal recessive with a mutation of the LIPA or LAL genes on 10q24-q25. TSD with impaired long-chain fatty acid oxidation have an autosomal recessive mutation in the ABHD5 gene (ABHydrolase Domain containing 5 on 3p21), which encodes an activating protein of the ATL (Adipose Triglyceride Lipase) enzyme.

Pathophysiology

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.

Diagnosis

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.

Clinical aspects

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 ...

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