What are Leukodystrophies?

Leukodystrophies are inherited, progressive disorders that affect the brain, spinal cord and peripheral nerves. The myelin sheath, the main component of the white matter is extremely complex. Myelin is the protective covering of the nerve cells and acts like insulation surrounding an electric wire. Myelin is made up of thousands of chemicals, each of which affects the myelin sheath in some way. Various leukodystrophies are caused by a deficiency of one of these chemical substances. Fifteen members of the family of leukodystrophies have been discovered to date:

18q Syndrome with deficiency of myelin basic protein
Acute disseminated encephalomyeolitis (ADEM)
Acute Disseminated Leukoencephalitis
Acute Hemorrhagic Leukoencephalopathy
Adrenoleukodystrophy (ALD)
Adrenomyeloneuropathy (AMN)
Aicardi-Goutieres Syndrome
Alexander Disease
Adult-onset Autosomal Dominant Leukodystrophy (ADLD)
Autosomal Dominant Diffure Leukoencephalopathy with neuroaxonal spheroids
Autosomal Dominant late-onset leukoencephalopathy
Childhood Ataxia with diffuse CNS Hypomyelination (CACH or Vanishing White Matter Disease)
Canavan Disease
Cerebral Autosomal Dominant Arteropathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
Cerebrtendinous Xanthomatosis (CTX)
Craniometaphysical dysplasia with leukoencephalopathy
Extensive Cerebral White Matter abnormality without clinical symptoms
Familial adult-onset leukodystrophy manifesting as cerebellar ataxia and dementia
Familial leukodystrophy with adult onset dementia and abnormal glycolipid storage
Globoid Cell Leukodystrophy (Krabbe Disease)
Hereditary adult onset leukodystrophy simulating chronic progressive multiple sclerosis
Lipomembranous osteodysplasia with leukodystrophy (Nasu Disease)
Metachromatic Leukodystrophy (MLD)
Megalencephalic leukodystrophy with subcortical cysts (MLC)
Neuroaxonal leukoencephalopathy with axonal spheroids
Oculodetatoldigital Dysplasia with cerebral white matter abnormalities
Orthochormatic leukodystrophy with pigmented glia
Ovarioleukodystrophy Syndrome
Pelizaeus Merzbacher Disease (X-linked spastic paraplegia)
Refsum Disease

Retinal Vasculopathy with Cerebral Leukodystrophy
Sjogren-Larssen Syndrome
Sudanophilic Leukodystrophy
Van der Knaap Syndrome (Vacuolating Leukodystrophy with Subcortical Cysts or MLC)
Vanishing White Matter Disease (Childhood ataxia with diffuse central nervous system hypomyelination, or CACH)
X-linked Adrenoleukodystrophy (X-ALD)
Zellweger Spectrum: Zellweger Syndrome
Neonatal Adrenoleukodystrophy
Infantile Refsum Disease

What are Lysosomal Storage Disorders?

Our bodies are made up of billions of cells. Lysosomes are each cell's recycling and detoxifying center. Their role is to break down complex material into simple products for recycling so that the cell can build new complex material. Storage within the lysosome occurs when the recycling process fails.

A deficiency in specific proteins (enzymes) is the usual cause of this failure. Over time, the amount of storage in the lysosome increases and leads to cell damage and severe physical symptoms as the material accumulates throughout the body. Lysosomal Storage Disorders are a group of more than 40 different genetic disorders that affect 1 in every 5000 persons, including both children and adults.

The severity of these diseases is variable. Some patients have a milder form of the disease and are not diagnosed until adolescence or adulthood. The clinical course is hard to predict. Babies with Lysosomal storage disorders usually appear normal at birth, but progressively develop symptoms in the first few months or years of life.

What is the Connection Between Lysosomal Storage Disease and Globoid Cell Leukodystrophy?

Children who have Krabbe Disease lack activity of the lysosomal enzyme galactosylceramidase (GALC). This enzyme deficiency produces inclusions of cerebroside and accumulation of psychosine, causing myelin loss and death of the cells responsible for nerve myelination. Demyelination causes central and peripheral nervous system degeneration and neurological symptoms.