Professional Documents
Culture Documents
Neurodegenerative Disorders of Childhood
Neurodegenerative Disorders of Childhood
Outcome
Fatal
Correct diagnosis
Genetic counselling
Neurodegenerative disorders of childhood
For all conditions in which the spesific enzyme
defect is known
Prevention by prenatal diagnosis ( chorionic vilus
sampling or amniocentesis) is possible
The inherited neurodegenerative disorders
Sphingolipidosis
Neuronal ceroid lipofuscinosis
Adrenoleukodystrophy
Sialidosis
Sphingolipidosis
Niemann-Pick disease
Gaucher disease
GM1 gangliosidosis
GM2 gangliosidosis
Krabbe disease
Metachromatic leukodystrophy
Niemann-Pick disease
Fatal disorder of infancy characterized by
Failure to thrive, hepatosplenomegaly and/or rapidly
progressive neurodegenerative course that leads to
death by 2-3 years of age
Six subtypes are described
Autosomal recessive
Deficient activity of sphingomyelinase (encoded by a
gene located on chromosome 11)
Pathologic accumulation of sphingomyelin and other
lipids in monocyte-macrophage system
Gaucher disease
Multisystemic lipidosis characterized by
Hematologic problems( trombocytopenia, anemia
Organomegaly
Skelatal involvement (bone pain, pathologic fractures)
3 clinical subtypes
Type 1: adult, non-neuropathic form
Type 2: infantile, acute neuropathic form
Type 3: juvenile
Gaucher disease
Autosomal recessive
Deficient activity of acid -glucosidase (encoded
by a gene on chromosome 1)
Accumulation of glycolipid substances,
particularly glucosyl ceramide in the cells of RES
Onset from early childhood to late adulthood
The pathologic hallmark
Gaucher cell in RES especially in bone marrow
Gangliosidoses
Gangliosides
Glycosphingolipids
Normal constituents of the neuronal and synaptic
membranes
Abnormalities in catabolism
An accumulation of the ganglioside within the cell
GM1 gangliosidosis
GM2 gangliosidosis
Gangliosidoses
GM1 gangliosidoses
Infantile : Type 1
Juvenile: Type 2
Adult : Type 3
Autosomal recessive
Deficiency of acid -galactosidase
Prenatal diagnosis is possible by measurement of
acid -galactosidase in cultured amniotic cells
Gangliosidoses
Infantile
Presents at birth or during the neonatal period
Anorexia, poor sucking, inadequate weight gain, generalized
seizures
Facial features are coarse
Macroglossia, prominent forehead, hepatosplenomegaly
Neurologic examination
Apathy, progressive blindness, deafness, spastic quadriplegia,
decerebrate rigidity
Cherry red spot in the macular region is visualized in 50% of cases
Juvenile GM2
g.
Adult GM2 g.
GM2 gangliosidosis
Tay-Sachs Disease
Affected infants appear normal until 6 months of age
Except startle reaction to noise soon after birth
Early hypotonia
Progressive spasticity
Juvenile
Progressive visual loss and intellectual impairment
between 5-10 years of age
Adrenoleukodystrophy
Often associated with adrenal cortical
insufficiency
X-linked recessive
Classic adrenoleukodystrophy (ALD)
5-15 years of age
Academic deterioration
Behavioral disturbances
Gait abnormalities
Generalized seizures
Spastic quadriplegia
Hypoadrenalism (%50)
Adrenoleukodystrophy
Adrenomyeloneuropathy
Slowly progressive
Spastic paraparesis, urinary incontinance and onset of impotance
during the 3rd or 4th decade
One of the most difficult problems in the management of X-linked
ALD is the common observation that affected individuals in the same
family may have quite different clinical coarses
Neonatal ALD
Marked hypotonia
Early onset of seizures
AR
Adrenal atrophy is evident post mortem
Correction of adrenal insufficiency is ineffective in halting neurological
deterioration
Sialidosis
AR
Accumulation of a sialic acid oligosaccharide complex secondary to
a deficiency in the lysosomal enzyme neuraminidase
Urinary excretion of sialic acid containing oligosaccharides is increased
Sialydosis type 1
Cherry red spot-myoclonus syndrome
Visual deterioration
Myoclonus
Sialydosis type 2
Infantile
Juvenile
Cherry red spots, myoclonus, somatic involvement, coarse facial features
Lymphocytes show vacuoles in the cytoplasm
Liver biopsy
Cytoplasmic vacuoles
Miscellaneous disorders
Multiple sclerosis (MS)
Multiple white lesions in the CNS
Rare in the pediatric population
Cause is unknown
Genetic, immunologic, infectious factors
Pathology
Demyelination with the formation of plaques
Miscellaneous disorders
Subacute Sclerosing Panencephalitis
Personality changes
Aggressive behaviour
Impaired cognitive function
Myoclonic seizures
Diagnosis
Measles Ab in CSF
EEG
Typical histological findings in the brain
Congenital abnormalities of Central
Nervous System (1)
The incidence of malformations is higher in children with
IUGR and multiple pregnancies
The same anomaly may occur as a result of genetic or
environmental causes
Etiology
Genetic factors
Forms of microcephaly inherited as AR
Sex-linked variety of hydrocephalus
Hereditary congenital facial paralysis AD
Some anomalies have a high risk of recurrence within families
Some anomalies are associated wiyh inborn errors of metabolism
Cytogenetic abnormalities
Most important group are the trisomies( e.g Down Syndrome)
Translocations, deletions
Maternal age
Maternal infections (rubella, CMV)
Congenital abnormalities of Central
Nervous System (2)
Neural tube defects
Anencephaly
Complete absence of the cerebral hemispheres
Females>males
Semilobar
Lobar
Anomalies of cell migration and abnormal surface
configurations of the brain (3)
Holoprosencephaly
In the most severe form there is an anterior holosphere
with no interhemispheric fissure and a single ventricle
The brain is often smaller than normal and olfactory
bulbs and tracts are absent
Optic nerves are absent and gyri are broad and have an
abnormal pattern
Brain stem and cranial nerve structures may be normal
Microcephaly
Small brain usually associated with a small head
Megalencephaly
Proportionate enlargement of the whole brain, usually
associated with the presence of a variable mental
aberration
Primary
Secondary
Agenesis of corpus callosum
May be part of a complex malformation or be
totally or partially absent in an otherwise normal
brain
It develops between the 12 and 22 weeks of
gestation
Mental retardation, mild to moderate, epilepsy
and cerebral palsy are common
Dignosis can be confirmed with a CT or MRI
Corpus callosum agenesis
Neurocutaneous
Tuberous sclerosis
syndromes
AD
The characteristic brain lesions conssist of tubers
Undergo calcification