Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ GLYCOLIPID STORAGE DISEASES ++ These are hereditary disorders in which one or more tissues become engorged with specific lipids because of deficiencies of the lysosomal enzymes required for hydrolysis of one of the glycosidic bonds. The type of lipid and its tissue distribution have a characteristic pattern in each disorder. In Gaucher disease (the most common disorder) and Niemann-Pick disease, major clinical manifestations result from macrophage accumulation of glucocerebroside and sphingomyelin, respectively, leading to their massive expansion in tissues. +++ GAUCHER DISEASE +++ Etiology and Pathogenesis ++ Result of a hereditary mutation in the GBA gene leading to dysfunction of a lysosomal enzyme, β-glucocerebrosidase, resulting in an accumulation of glucocerebroside. Inheritance is autosomal recessive, with high gene frequency among Ashkenazi Jews. More than 850 different mutations of the GBA gene have been reported. Among those of Ashkenazi Jewish origin, the predominant mutation is N370S, which accounts for approximately 75% of mutant alleles. This mutation occurs in 30% of non-Jewish patients. It usually gives rise to mild disease in the homozygous form. The second most common mutation is L444P, which when homozygous accounts for most patients with neuronopathic disease and is the most prevalent mutation in Asians, Arabs, and Norrbottnians. +++ Clinical Features ++ Three types of Gaucher disease are recognized based on absence (type 1) or presence of neurologic features (types 2 and 3) (Table 37–1). — Type 1 occurs in both children and adults and is primarily caused by an accumulation of glucocerebroside-laden macrophages in the liver, spleen, and marrow. Neurologic manifestations are rare and primarily affect the peripheral nervous system. — Type 2 is exceedingly rare and is characterized by rapid neurologic deterioration and early death. — Type 3, or juvenile Gaucher disease, is a subacute neuropathic disorder with later onset of symptoms and better prognosis than type 2. Patients may be asymptomatic, or symptoms may range from minimal to severe: — Chronic fatigue is common. — Hemorrhage occurs after surgical procedures. — Splenic enlargement may cause positional symptoms. Hepatomegaly is usually asymptomatic. — Skeletal lesions are often painful. “Erlenmeyer flask” deformity of the femur is common (Figure 37–1). ++Table Graphic Jump LocationTABLE 37–1CHARACTERISTICS OF THE THREE TYPES OF GAUCHER DISEASEView Table||Download (.pdf) TABLE 37–1 CHARACTERISTICS OF THE THREE TYPES OF GAUCHER DISEASE Type 1 Type 2 Type 3 Subtype Asymptomatic Symptomatic Neonatal Infantile 3a 3b 3c Common genotype N370S/N370S or two mild mutations N370S/other or two mild mutations Two null or recombinant mutations One null and one severe mutation No mutation L444P/L444P D409H/D409H Ethnic predilection Ashkenazi Jews Ashkenazi Jews None None None Norrbottnians, Asians, Arabs Palestinian Arabs Common presenting features None Hepatosplenomegaly, hypersplenism, bleeding, bone pains Hydrops fetalis; congenital ichthyosis SNGP, strabismus, opisthotonus, trismus SNGP; myoclonic seizures SNGP; hepatosplenomegaly growth retardation SNGP; cardiac valve calcifications Central nervous system involvement None None... Your Access profile is currently affiliated with '[InstitutionA]' and is in the process of switching affiliations to '[InstitutionB]'. Please click ‘Continue’ to continue the affiliation switch, otherwise click ‘Cancel’ to cancel signing in. Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free a profile for additional features.