Metachromatic leukodystrophy: pediatric presentation and the challenges of early diagnosis.

Metachromatic leukodystrophy (MLD; OMIM 250100) is an autosomal recessive hereditary disease caused by a deficiency of the Arylsulfatase A (ARSA) enzyme and, more rarely, of Saposin B, which is responsible for the interaction with the sulfatide, allowing the ARSA to degrade it. Therefore, it is classified as a hereditary metabolic disorder that evolves with a reduction of sulfatide degradation. Initially, the disease was known as “diffuse cerebral sclerosis” and, in 1938, it was named “metachromatic leukodystrophy” and classified as a lipidosis in 1958 and 1959, based on the discovery of a high concentration of sulfatídes (3-O-Sulfogalactosylceramide) (Figure 1) demonstrated by Jatzkewitz and Austin1.2. ARSA deficiency causes metachromatic lipids to accumulate on the white matter of the central and peripheral nervous system, which is responsible for causing demyelination and may also affect organs such as the kidneys, gall bladder, spleen, and other visceral ones1-3. There are different variants (leading to different levels of residual enzymatic activity) and variations regarding the age of onset of the first symptoms and speed of disease progression, thus, it has been classified as: infantile (late infantile, 0 to 4 years), juvenile (4 to 15 years), and adult (over 15 years) (Annex 1)3.4. In addition, the diagnosis can be suspected when the patient begins to show signs of loss of intellectual,