Teaching Case

This mentally retarded patient was referred to the hospital with stable angina pectoris and peripheral oedema.The patient also had carpal tunnel syndrome on the right side and left-sided anacusis.

This mentally retarded patient was referred to the hospital with stable angina pectoris and peripheral oedema.The patient also had carpal tunnel syndrome on the right side and left-sided anacusis. ECG examination revealed signs of left ventricular hypertrophy. After medical treatment, right and left coronary angiography was performed. There was 70% stenosis of the left anterior descending coronary artery and 40% stenosis of the right coronary artery. The patient had previously been diagnosed with Hunter’s syndrome.

A control MRI of the cranium was performed on a 1.5 T MR scanner, in three planes, with SE T1 and FSE T2 sequences. The examination revealed well-marginated foci (cyst- or spindle-like areas) in the subcortical and deep cerebral white matter of the frontoparietal region. These were isointense on all sequences to CSF. The subarachnoid spaces of the right frontoparietal lobes seemed to be widened discordant with the age of the patient.

The mucopolysaccharidoses (MPS) are a group of diseases caused by deficiency of lysosomal enzymes involved in the degeneration of glycosaminoglycans. Undegraded glycosaminoglycans accumulate in lysosomes and affect tissue function. MPS have been divided into seven major types. The classification is based on the deficient enzyme responsible for the disease. These disorders carry such eponyms as Hurler, Scheie, Hurler-Scheie, Hunter, Sanfilippo, Morquio, Maroteux-Lamy and Sly. They share many clinical features, including multiple system involvement, organomegaly, dysostosis multiplex, facial abnormalities, hearing and vision loss, joint involvement, cardiac involvement and central nervous system involvement. Cardiac diseases include myocardial hypertrophy, pulmonary and systemic hypertension, valvular disease, coronary occlusion and myocardial infarction. Congestive heart failure and sudden death are relatively frequent. Profound mental retardation may be found in Hurler, Hunter's and San Filippo syndromes (MPS Types I, II and III), but normal intellect may be retained in other MPS and some mildly affected Hunter patients. Although each type differs clinically, generally, people with mucopolysaccharidoses experience a period of normal development followed by a decline in physical and/or mental function.

In Hunter syndrome the genetic defect is a deficiency of iduronate 2-sulphatase, a lysosomal enzyme which catalyses the breakdown of heparan sulphate (HS) and dermatan sulphate (DS). Incomplete degradation of HS and DS results in accumulation of these products in the CNS and peripheral tissues. The incidence of the disease is 1/100,000. The genetics of Hunter's disease differ from the other mucopolysaccharidoses as the disorder is inherited as an X-linked recessive (all the other types are autosomal recessive disorders).There are two clinical variants: MPS IIA (severe form) and MPS IIB (mild form), which represent the two ends of a wide spectrum of clinical severity. The two forms cannot be distinguished by enzymatic analysis. Signs of the severe form are joint stiffness, mental deterioration, dwarfing, and progressive deafness. Death usually occurs by age 15. Symptoms of the mild form include short stature, limitation of motion, and features such as an enlarged forehead, lips and tongue, and misaligned teeth. Life span may be normal. Diagnosis of the disease is based on elevated HS and DS levels on 24-hour urine collection and decreased iduronate 2-sulphatase activity in leukocytes and cultured skin fibroblasts.

Imaging findings in Hunter's disease include the following. The hands are osteopaenic with short, wide metacarpals and phalanges. The distal radius and ulna are slanted towards each other in a "V" shape. The chest has short, thick clavicles and oar-shaped ribs. Ovoid vertebral bodies are seen in the thoracic spine with an associated thoracolumbar scoliosis. Flared iliac wings and shallow acetabulae are present along with coxa valga and flaring of the femoral metaphyses. An enlarged, elongated calvarium with widened coronal sutures is present and there is a J-shaped deformity of the sella.

Imaging studies of the brain in the MPS demonstrate delayed myelination, atrophy, varying degrees of hydrocephalus and white matter changes. The white matter abnormalities are manifested as diffuse low attenuation within the cerebral hemispheric white matter on CT and as focal and diffuse areas of prolonged T1 and T2 relaxation times on MRI studies. The sharply defined foci are commonly present in the corpus callosum, basal ganglia and cerebral white matter. They are isointense to CSF on all sequences, and are probably enlarged perivascular spaces filled with mucopolysaccharide or CSF. With progression of the disease, the lesions become larger and more diffuse, reflecting the development of infarcts and demyelination. Death is usually due to obstructive airways disease, cardiac failure, and/or neurological complications.