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An unusual case of chronic renal failure

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An unusual case of chronic renal failure

Q1: What does the mri scan show (see p 104)?

The MRI scan of the brain shows generalised cerebral and cerebellar atrophy. There is a quite extensive abnormal high signal on the T2-weighted images and fluid attenuated inversion recovery (FLAIR) sequence in both the cerebellar hemispheres, pons, and in the cerebral white matter involving both periventricular and subcortical areas. These appearances are not specific but are likely to be due to widespread ischaemic changes.

Q2: What is shown in fig 3 (see p 104)?

Angiokeratomas. These are vascular lesions of the skin, which usually appear at puberty, increase, with age, and are mainly confined to the bathing trunk area. These occur as a result of ectatic dilatation of the blood vessels weakened by endothelial deposition of ceramide.

Q3: What is the diagnosis?

Fabry's disease.

Q4: What do you expect to see in the electron microscopic examination of the kidney?

Multilamellar bodies (zebra bodies).

Q5: What investigation will you do to confirm the diagnosis?

The α-galactosidase levels should be measured as they are diagnostic. In our patient the α-galactosidase levels were undetectable.

Discussion

Fabry's disease is a rare (1:40 000) X linked recessive disorder in which partial or total deficiency of lysosomal α-galactosidase results in the progressive accumulation of glycolipids in various tissues including the kidneys. The single most debilitating symptom of Fabry's disease is the pain. The painful crises most often begin in childhood and consists of agonising burning pain initially in the palms and soles which often radiates to the proximal extremities and other parts of the body. Cardiac manifestations include anginal chest pain, myocardial ischaemia, and infarction, congestive cardiac failure, and cardiac enlargement. The electrocardiogram may show left ventricular hypertrophy, ST segment changes, and T wave inversion. Short PR intervals have been reported.1 Cerebrovascular manifestations result primarily from multifocal small vessel involvement and may include personality changes, psychotic behaviour, thrombosis, seizures, aphasia, hemiplegia, etc.2 Progressive glycosphingolipid deposition in the kidney results in proteinuria and other signs of renal impairment with gradual deterioration of renal function and developmentof azotaemia in middle age. Ocular involvement is most prominent in the cornea (opacities), lens (cataract), conjunctiva, and retina (vascular lesions). Other clinical features include lymphoedema, episodic diarrhoea, avascular necrosis of the head of femur, delayed puberty, fine facial and body hair, dyspnoea, and wheezing respiration.3 Treatment of patients with regard to cardiac, pulmonary, and central nervous system manifestations remain non-specific and symptomatic. Since renal insufficiency is the most frequent late complication in patients with this disease, chronic haemodialysis and/or renal transplantation have become life saving. At present the most practical and effective therapy is preventive screening of all suspect heterozygotes, genetic counselling, and prenatal diagnostic studies should be made available to all at risk families. Enzyme replacement has been shown to be beneficial over short term in small studies. With recent developments in molecular genetics it is possible to produce the human recombinant enzyme α-galactosidase. In addition the results of a trial of gene therapy in a Fabry's disease gene knocked out mouse appear promising.4

Final diagnosis

Fabry's disease.

References

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