Leukodystrophies are a group of usually inherited disorders characterized by degeneration of the white matter in the brain. The word leukodystrophy comes from the Greek roots leuko, "white", dys, "abnormal" and troph, "growth". The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty insulating covering around nerve fibers. Leukodystrophies may be classified as hypomyelinating or demyelinating diseases, depending on whether the damage is present before birth or occurs after. Other demyelinating diseases are usually not congenital and have a toxic or autoimmune cause.When damage occurs to white matter, immune responses can lead to inflammation in the central nervous system (CNS), along with loss of myelin. The degeneration of white matter can be seen in an MRI scan and used to diagnose leukodystrophy. Leukodystrophy is characterized by specific symptoms including decreased motor function, muscle rigidity, and eventual degeneration of sight and hearing. While the disease is fatal, the age of onset is a key factor, as infants have a typical life expectancy  of 2–8 years, while adults typically live more than a decade after onset. Treatment options are limited, although hematopoietic stem cell transplantations using bone marrow or cord blood seem to help in certain types while further research is being done. The combined incidence of the leukodystrophies is estimated at 1 in 7,600. The majority of types involve the inheritance of an X-linked recessive, or X-linked dominant trait, while others, although involving a defective gene, are the result of spontaneous mutation rather than genetic inheritance.
Metachromatic leukodystrophy
Metachromatic leukodystrophy is the result of genetic defects in the enzymes associated with the cellular compartment the lysosome. MLD is one of two leukodystophies that are also a lysosomal storage disorder. MLD is inherited in an autosomal recessive way and is the result of mutations in three different ARSA alleles that encode the enzyme arylsulfatase A (ASA or sometimes ARSA), also called sulfatide sulfatase. ASA is responsible for the breakdown of sulfatides, sphingolipids present in neuronal membranes as well as in myelin. When there is a mutation in the gene that encodes ASA, the result is it decreases production, which subsequently leads to diminished degradation of sulfatides, thus causing them to accumulate. This accumulation of sulfatides is poisonous to oligodendrocytes, the myelin-producing cells of the CNS, effectively leading to a disturbance in myelin structure followed by demyelination. The pattern of inheritance of the three different alleles affects what type of MLD a person develops. Two null alleles are responsible for the infantile version, and do not allow for any production of ASA. A heterozygous individual (one null allele, one non-null allele) develops the juvenile form and sees some production of ASA, while an individual with two non-null alleles (but still mutated) develops the adult form. Krabbe disease
Like MLD, Krabbe disease is another type of leukodystrophy with autosomal recessive inheritance that is the result of a lysosomal storage disorder. It is due to a deletion in exon 16 of the GALC gene that causes a frameshift mutation leading to a premature stop codon.