Many metabolic diseases involving white and gray matter show a neurodegenerative clinical course.
• Sphingolipidoses
GM 1/2 ganliosidosis
Krabbe disease
metachromatic leukodystrophy
• Neuronal ceroid lipofuscinosis (most common)
• Adrenoleukodystrophy
• Sialidosis
• Others; Pelizaeus-Merzbacher disease (X recessive-myelin disorder-Nystagmus-optic atrophy-dysarthria), Alexander disease, Canavan spongy degeneration, Kinky hair disease, Rett syndrome, and subacute sclerosing panencephalitis
The most important symptoms of neurodegenerative diseases are; Speech, vision, hearing or movement loss and neurological dysfunction are often accompanied by seizures, feeding difficulties and mental retardation.
Upper motor neuron findings and progressive spasticity are observed in white matter involvement, and convulsion, intellectual and visual impairment are observed in the early stages of gray matter involvement.
Neuronal Ceroid Lipofusinosis
Neuronal ceroid lipofuscinosis is an inherited neurodegenerative lysosomal storage disease. The disease takes its name from the ceroid and lipofuscin accumulated in the cell. It is characterized by vision loss, progressive dementia, seizures, impaired motor function, and early death.
Neuronal ceroid lipofuscinoses are the most common neurodegenerative disease group in children.
It consists of three autosomal recessive diseases.
Infantile Type (Haltia-Santavuori); Myoclonic seizures, which usually begin at age 1 (6-24 months), begin with intellectual deterioration and blindness. Retinal examination reveals optic atrophy and brownish discoloration of the macula, and cerebellar ataxia is evident. Death occurs at about 10 years old. It occurs as a result of a recessive mutation in the CLN1 gene, which is involved in the synthesis of the lysosomal enzyme Palmitoyl-protein thioesterase-1 (PPT-1). Enzyme tests can be done for diagnosis.
Late Infantile Type (Jansky-Bielschowsky); The initial sign is myoclonic seizures, which begin between 2 and 4 years of age in a previously normal child. Tripeptidyl peptidase-1 (TPP-1) enzyme defect occurs as a result of CLN2 mutation. Dementia and ataxia are associated with progressive loss of visual acuity and microcephaly. Retinal examination reveals optic atrophy and brownish discoloration of the macula. Electron microscopic examination of skin or conjunctival biopsy material typically shows "curvilinear bodies" caused by stored material.
Juvenile Type (Spielmeyer-Vogt); It is the most common type of neuronal ceroid lipofuscinosis. It is caused by an autosomal recessive mutation in the CLN3 gene. The patient shows normal development for the first 5 years and is healthy. It is characterized by progressive vision loss and intellectual impairment beginning between the ages of 5 and 10 years. Retinal examination reveals optic atrophy and brownish discoloration of the macula. Patients die in their late 20's and early 30's. In tissue biopsy, deposits are seen as "fingerprint profiles" with electron microscopy. Vacuoles can be seen in lymphocytes on light microscopy.
Alexander's Disease
• It is a rare disease with progressive macrocephaly and leukodystrophy.
• GFAP (Glial fibrillary acidic protein) gene has OD mutation.
• He has a disease of the white matter and has astrocyte dysfunction. It mostly involves the frontal region.
• It may show infantile, juvenile or adult onset.
• In its infantile form, it results in progressive megaloencephaly, psychomotor retardation, optic atrophy, spasticity, resistant convulsions and death (usually 5 years of age).
• Brain biopsy shows eosinophilic Rosental fibers.
Rett Syndrome
• It is a disease mainly seen in girls, in which regression in brain growth and associated microcephaly, slowdown in development and regression occur after a normal neonatal period and generally after the first year of age.
• Brain weight (60-80% of normal), number of synapses, dentin length and branching are decreased.
• The disease occurs as a result of the MeCP2 mutation. It occurs de novo in almost all cases (99%). In addition, the mutation is thought to be of paternal origin. It is fatal in men.
• Regression and ataxic gait in tongue and motor steps, fine tremor in hand movements are observed.
• Most children experience strange breathing with sighing, intermittent apnea and accompanying cyanosis.
• The finding unique to Rett syndrome is repetitive hand flapping and loss of purposeful and spontaneous use of the hands.
• Autistic behaviors seen in all patients are a typical finding. Generalized tonic-clonic convulsions are present in most of them.
• Cardiac arrhythmias and sudden death are more common than in the general population. Girls usually reach adulthood.
• Atypical Rett syndrome is a condition characterized by severe myoclonic seizures, developmental arrest and regression in the infant period and in which an X-linked inherited CDKLS mutation is seen.
Menkes Kinky Hair Syndrome
• It is a disease characterized by impaired absorption and transport of copper and dysfunction of copper-containing enzymes.
• X-linked recessive inheritance.
xq21. Mutation of the ATP7 A gene located in region 1 is responsible.
It is very rare in girls and symptoms are milder.
• Cytochrome oxidase c (mitochondrial), superoxide dismutase, dopamine hydroxylase, tyrosinase, lysyl oxidase and monoaminoxidase are deficient.
• Defects in energy production, tendency to infections, structural disorders in the skin and vessels, and neurotransmitter imbalance are observed.
• Neuronal decrease in cortex and cerebellum, demyelination in white matter are detected.
• Symptoms begin in the first few months of life. Pallor, hypothermia, convulsions, hypotonia, feeding difficulties, optic atrophy, severe mental retardation can be seen in the clinic.
• In the diagnosis, microscopic examination of the hair and fractures (trichorrhexis nodosa) in the shafts of the hair follicles and pili torti, low ceruloplasmin and copper in the blood are important.
• Untreated cases die at the age of 3 years.
• Progressive loss of cerebral tissue, degeneration of gray matter and cerebellum are seen in brain biopsy.
• Copper-histidine injection is applied in the treatment. It should be started within the first 10 days of life.
• Occipital Horn syndrome: It is a disease that occurs with different mutations in the same gene as Menkes disease, has a milder course, and also causes skeletal dysplasias.
Canavan's Disease
• It is a disease characterized by spongy changes in the brain.
• OR indicates transition.
• N acetylaspartic acid accumulates in tissues due to aspartoacylase deficiency. Increased excretion of N-acetyl aspartic acid in the urine.
• The infantile form is characterized by megaloencephaly, hypotonia and developmental arrest in the first month of life.
• Spasticity increases, death occurs at 3-4 years of age as a result of extensor posture, blindness and autonomic failure.
• The juvenile form is characterized by ataxia, dementia, tremor and spasticity, optic atrophy and blindness after 5 years of age.
• Only supportive treatment is applied.
