A4-month-old boy presents with painful progressive joint deformity (particularly the ankles, knees, elbows, and wrists), hoarse crying, and granulomatous lesions of the epiglottis and larynx leading to feeding and breathing difficulty. Biopsy of the liver indicates an accumulation of ceramides. The observed symptoms and the results of the liver biopsy are indicative of which disease?
(A) Farber lipogranulomatosis
© Gaucher disease
(D) metachromic leukodystrophy
(E) Sandhoff-Jatzkewitz disease
(A) Farber lipogranulomatosis is characterized by painful and progressively deformed joints and progressive hoarseness due to involvement of the larynx. Subcutaneous nodules form near the joints and over pressure points. Granulomatous lesions form in these tissues and there is an accumulation of lipid-laden macrophages. Significant accumulation of ceramide and gangliosides is observed, particularly in the liver. If these compounds accumulate in nervous tissue there may be moderate nervous dysfunction. The illness often leads to death within the first few years of life, although milder forms of the disease have been identified. Fucosidosis (choice B) is characterized by the accumulation and excretion of glycoproteins, glycolipids, and oligosaccharides-containing fucoside moieties. Symptoms of fucosidosis include psychomotor retardation, dystosis multiplex (a term referring to multiple skeletal abnormalities), growth retardation, and coarse facial features. Gaucher disease (choice C) is characterized by an accumulation of glucosylceramide (glucocerebroside). Several forms of the disease have been identified and vary in severity. Typical symptoms include hepatosplenomegaly, bone lesions, and CNS involvement. Occasionally, the lungs and other organs may be involved. Metachromic leukodystrophy (choice D) is a disorder of myelin metabolism. It is characterized by the accumulation of galactosyl sulfatide (cerebroside sulfate). Symptoms may appear at any age and include mental regression, urinary incontinence, blindness, loss of speech, peripheral neuropathy, and seizures. SandhoffJatzkewitz disease (choice E) is a disorder related to Tay-Sachs disease. It is characterized by a defect in the degradation of GM2 gangliosides with symptoms of severe mental retardation, blindness, and early mortality.