undertaken and holds some promise.54 Mucopolysaccharidosis Type VI (MaroteauxLamy Syndrome) Deficiency of arylsulfatase b results in an inability to hydrolyze the sulfate groups in dermatan sulfate The clinical picture is similar to that of Hurler syndrome, but normal intelligence is usual Although severe in its classical form, milder variations exist Affected infants can present acutely with cardiomyopathy.55 The mitral and aortic valves are frequently involved and the disease is typically progressive Regurgitation is the primary valve disorder, but stenosis or a combination or stenosis and regurgitation will become more common over time Valvar dysfunction severe enough to necessitate replacement has been noted in young adults.56 Left ventricular aneurysm has also been reported.57 Death usually occurs in the third decade The condition is inherited in an autosomal recessive fashion, although some cases have been presumed to be X-linked.58 Enzyme replacement therapy with human recombinant arylsulfatase b has been studied and found to be effective in terms of arresting the progression of cardiac valve disease when started late in life, but it is postulated that it may have even better efficacy if started in early infancy.59,60 Mucopolysaccharidosis Type VII (Sly Syndrome) Deficiency of β-glucuronidase results in a clinical syndrome of extremely variable severity Included in the features are coarse facies, corneal clouding, abdominal and inguinal hernias, puffy hands and feet, hepatosplenomegaly, and a small thoracolumbar hump Cardiovascular manifestations include hypertension, aortic aneurysm, valve thickening, aortic regurgitation, obstructive arterial disease including coronary involvement, and cardiomyopathy.61–63 Fetal hydrops has also been reported.64 This extremely rare condition is inherited in autosomal recessive fashion Duration of survival varies widely and depends on the severity of the disease Death as early as 30 months has occurred in one child with severe disease Animal studies involving enzyme replacement therapy have been performed and are encouraging in terms of improving the cardiovascular changes associated with this disease.65 Mucolipidoses The mucolipidoses present with clinical features similar to the mucopolysaccharidoses but are biochemically distinct Leroy and Demars66 observed inclusions in cultured fibroblasts that occupied the whole cytoplasmic space apart from the Golgi apparatus It was because of this that the name inclusion-cell, or i-cell, disease was coined The cause of the lysosomal storage defect is deficiency of several acid hydrolases in the lysosome, but this is not the primary problem, since the plasma abounds in these acid hydrolases (albeit in unstable forms) The problem is failure to locate the hydrolases within the lysosome Failure of phosphorylation of mannose residues of the hydrolases is the primary defect Hydrolases without mannose 6-phosphate components are then not recognized by the lysosome and are not transported across the lysosomal membrane, particularly in connective tissue In this way, inclusioncell disease and pseudo-Hurler polydystrophy differ from sialidosis (previously called mucolipidosis type I), where there is a single lysosomal enzyme defect Mucolipidoses types II (inclusion-cell disease) and III (pseudo-Hurler polydystrophy) result from a deficiency of uridine diphosphate (udp)-nacetylglucosamine:lysosomal enzyme n-acetylglucosamine-1phosphotransferase The degree to which this enzyme is deficient determines the ultimate phenotype Diagnosis is suggested by clinical features resembling mucopolysaccharidoses but without their biochemical abnormalities Findings of high serum levels of β-hexosaminidases, iduronate sulfatase, and arylsulfatase are diagnostic The characteristic enzymatic deficiencies in fibroblasts can be identified in cultured cells Mucolipidosis Type II (Inclusion-Cell Disease, ICell Disease) Inclusion-cell disease is an autosomal recessive condition that results from a severe deficiency of the phosphotransferase enzyme due to specific gene mutations that result in a marked reduction in enzyme activity Various defects in the gene encoding this enzyme have been discovered in patients with this disorder.67 Patients with inclusion-cell disease present with clinical features very similar to those of Hurler syndrome Hepatosplenomegaly is not so obvious, whereas striking gingival hypertrophy is a feature not encountered in Hurler syndrome Furthermore, the disease becomes evident earlier than does Hurler syndrome Corneal clouding is the rule The skeletal and joint abnormalities, together with myocardial infiltration, usually lead to death by the age of 5 years either from respiratory causes or cardiac failure All children have cardiac involvement, frequently with thickening and insufficiency of the mitral valve and, less frequently, the aortic valve.68 Asymmetric septal hypertrophy has been reported.69 Treatment of the cardiac manifestations is usually supportive, although surgical management of valve involvement has been reported.70 Also, success with allogeneic stem cell transplantation in terms of disease progression has been reported in a small number of cases.71 Mucolipidosis Type III (Pseudo-Hurler Polydystrophy) Mucolipidosis type III is an autosomal recessive condition that is less severe, and also less common, than type II and is due to a deficiency of the same phosphotransferase enzyme However, in this type the enzyme activity is less severely reduced and the manifestations are less severe There is significant variability in the clinical severity of this disease.72 This is likely due to various genetic defects leading to different levels of enzyme activity Patients are usually spared the joint manifestations early in life (unlike those with inclusion-cell disease) and often present with joint stiffness at the age of 4 or 5 years Growth is moderately retarded and corneal clouding is present by the age of 7 or 8 years The patients are disabled by carpal tunnel syndrome and destruction of the hip joints Cardiac involvement, typically gradual thickening and eventual regurgitation of the mitral and aortic valves, does occur but is usually not sufficiently severe to cause clinical problems Patients with pseudo-Hurler polydystrophy generally survive into the fourth decade More recently, with advances in understanding of the genetics of the disease, mucolipidosis has been subcategorized into type III α/β and type III gamma as the deficient enzyme is the product of two genes The first encodes the α and β subunits and the second encodes the gamma subunit Despite this, the two subtypes have similar manifestations.73,74 Disorders of Glycoprotein Degradation Specific lysosomal enzymatic deficiencies result in failure of degradation of