A complex group of inherited disorders of lipid
metabolism resulting in systemic deposition of triglycerides and, to a
lesser extent, cholesterol.
TSD type III: Wolman Disease; Lysosomal Acid Lipase Deficiency;
Acid Cholesteryl Ester Hydrolase Deficiency, Wolman type; Cholesteryl Ester
TSD with Impaired Long Chain Fatty Acid Oxydation: Ichthyotic
Neutral Lipid Storage Disease; Dorfman-Chanarin Syndrome; Chanarin-Dorfman
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.
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.
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.
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.
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 ...