Batten Diseases and Lipidoses
Disorders of lysosomes result from a lack of enzymes or critical proteins involved in lysosomal function. The lysosomes act as the recycle and incinerator systems of our cells. The lack of an enzyme or critical protein can lead to disturbed cellular function resulting from accumulation of substrate (cellular garbage or accumulation of aberrant protein) or from altered cellular metabolism. These usually lead to cell death, but the timing differs depending on the disease. The Batten diseases, neuronal ceroid lipofuscinoses, are perhaps the most extreme of these disorders leading to early cell death and degeneration of the central nervous system (CNS). The fact that the CNS is predominately affected by these disorders probably reflects the lack of regenerative capability in this organ.
BATTEN DISEASES: NEURONAL CEROID LUPOFUSCINOSES
The neuronal ceroid lipofuscinoses (NCL) are a group of recessively inherited degenerative CNS disorders that are accompanied by the accumulation of a lipid protein complex in the neuronal and retinal lysosome. This lipid protein complex stains brown under certain conditions (thus the name lipofuscin; they also autofluoresce) within the neuronal and retinal lysosomes. These disorders are actually multisystemic, and inclusions can be seen in many tissues. NCLs result from deficits in lysosomal proteins; some are enzymes, and others are membrane-associated proteins of unknown function. The diseases manifest at different ages, have variable disease progression, and have different genetic causes. Table 564-1 provides a description of various forms of NCL.
TABLE 564-1NEURONAL CEROID LIPOFUSCINOSIS (NCL) BY AGE OF ONSET AND CLINICAL PRESENTATION |Favorite Table|Download (.pdf) TABLE 564-1NEURONAL CEROID LIPOFUSCINOSIS (NCL) BY AGE OF ONSET AND CLINICAL PRESENTATION
|Disorder ||Gene ||Protein ||Age of Onset ||Lysosomal Inclusions ||Seizure Type ||Degeneration |
|Congenital NCL ||CLN10 ||Cathepsin D ||Birth to teen ||Osmophilic granular ||Seizures present in the congenital form ||Rapid to slow with vision loss |
|Infantile NCL ||CLN1 ||Palmitoyl-protein thioesterase ||First or second year ||Osmophilic granular ||Myoclonic ||Rapid |
|Late infantile NCL ||CLN2 ||Tripeptidyl peptidase 1 ||Second or third year ||Curvilinear multilamellar ||Generalized tonic-clonic, absence, drop attacks, late: nonepileptic myoclonus ||Over 2–3 years, vision loss late |
|Other late infantile NCLs ||CLN5, CLN6, CLN7 ||Membrane-bound lysosomal proteins ||Second or third year ||Granular, curvilinear, and osmophilic ||Generalized tonic-clonic, absence, drop attacks ||Rapid to 2–3 years, vision loss |
|Juvenile NCL (Batten disease) ||CLN3 ||Membrane-bound lysosomal protein ||First decade (around age 5 years) ||Lipofuscin, fluorescent lipoprotein ||Generalized tonic-clonic, absence ||Slowly progressive over decades, prominent early vision loss |
|Progressive epilepsy with intellectual disability (also known as northern epilepsy) ||CLN8 ||Membrane-bound lysosomal and endoplasmic reticulum protein ||First decade (5–10 years) ||Lipofuscin, fluorescent lipoprotein, fingerprint curvilinear ||Generalized tonic-clonic ||Very slowly progressive over many decades, death in middle age |
|SCAR7 ||CLN2 ||Tripeptidyl peptidase 1 ||Adolescence ||Unknown ||No seizures ||Progressive ataxia |
These were first described by Dr. Frederick Batten, a British pediatrician, and although juvenile NCL is named after ...