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A severe form of lysosomal acid lipase deficiency characterized by rapidly progressive lipid accumulation in organs and tissues that presents in the neonatal or infantile period with massive hepatosplenomegaly, liver failure, diarrhea/steatorrhea and vomiting.
ORPHA:75233Classification level: Subtype of disorder
Approximately 50 cases have been reported in the literature.
The disease can sometimes present in the fetus (hepatomegaly, ascitis, calcified adrenal glands), but onset more typically occurs in the first weeks of life with abdominal distension and major or even massive hepatosplenomegaly (which can occur in the neonatal period) and sometimes ascites. The presence of calcified adrenal glands (as revealed by radiography), is a common and very characteristic sign. . Children present with significant digestive disorders (such as vomiting and diarrhoea with steatorrhoea), which can lead to a sudden arrest of ponderal growth and progressive psychomotor degradation in the absence of specific neurological signs. Later, severe anemia and cachexia become apparent.
The enzymatic deficiency results from severe mutations of the acid lipase gene (LIPAor LAL), localised to 10q24-q25.
The diagnosis can be rapidly confirmed by measuring enzymatic activity in leucocytes or dried blood spots , revealing an almost total deficiency.
Differential diagnosis includes familial hemophagocytic histiocytosis and other phagocytic syndromes, Gaucher disease type II, Niemann-Pick disease type A, and malignancies such as leukemia or neuroblastoma.
Prenatal diagnosis can be performed by measuring enzymatic activity or by mutational analysis of chorionic villi or amniocytes.
The disease follows an autosomal recessive pattern of inheritance.
Management and treatment
Enzyme replacement therapy with sebelipase lipase is available in the US and the European union and has been shown to prolong survival. Very early bone marrow or cord blood transplant has also been used and has provided some benefit in a limited number of cases.
In the absence of definitive therapy, few children survive beyond one year of age. Enzyme replacement therapy, if started in a timely fashion, may prolong survival but the long term impact remains unknown.
- Clinical genetics review
- English (2016)