Anaesthesia recommendations for Metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by a gene mutation resulting in the reduced production of the enzyme arylsulfatase A (ASA). This deficiency results in the accumulation of sulfatides in the lysosomal deposits in the central and peripheral nervous system, which results in demyelination. It is a rare disease seen in 1-4:100,000. There are three clinical subtypes, based upon age of onset of the first symptoms: late infantile, juvenile and adult forms. The late infantile subtype occurs before 30 months of age, with psychomotor regression resulting in ataxia and areflexia. Peripheral neuropathy can be the initial symptom, before central progression. As it progresses, it leads to dysphagia, drooling and the requirement of a gastrostomy for feeding. Painful spasms and seizures are common and death occurs within a few years. The initial symptoms of adult-onset MLD include memory loss and emotional instability with slower progression to the neurological deficits seen in the juvenile forms. Non-neurological symptoms result from the accumulation of sulfatides in visceral organs. This can lead to gallbladder issues such as gallstones and cholecystitis. Other organs affected include liver, kidney, pancreas and intestines. The diagnosis of MLD is determined by progressing neurological dysfunction, widespread white matter changes in MRI, ASA enzyme deficiency in leucocytes, elevated urinary excretion of sulfatides as well as mutation analysis. There are currently no curative treatment options for symptomatic patients with MLD. Haematopoietic stem-cell transplantation has been tested but results have been inconclusive. Gene therapy is approved for use in presymptomatic or very mildly affected children with the late infantile or early juvenile form of MLD. [ABSTRACT FROM AUTHOR]