Neuronal ceroid lipofuscinosis infantile type. Santavuori-Haltia-Hagberg disease
Incidence
It is a rare autosomal recessive disorder with a wide spread geographical distribution but strongly centered in Finland with an incidence of one in 20,000. The gene is located in the short arm of chromosome 1.
Clinical Characteristics
The most striking feature is the rapidity by which leads to a widespread destruction of neurons very rarely seen in other metabolic encephalopathies. Neurological deterioration results in myoclonus, ataxia, visual failure, progressive brain atrophy and early loss of electrocortical activity. Before the end of the third year, the child becomes completely unresponsive. The onset is usually between 12 and 18 months with arrest and then regression of all psychomotor acquisitions. Some children look already retarded by eight months of age. Children may look initially apathetic, dull, with diminished activity. Some children display autistic behavior with complete loss of contact with their surrounding but maintaining gestural stereotypes particularly knitting movements. Simultaneously or later, other neurological signs rapidly appear and progress. Incoordination of limbs make impossible for patient to walk or stand. There is generalized hypotonia with normal or exaggerated deep tendon reflexes. Myoclonic jerks appear soon and are a constant feature always before the end of the second year. Occasionally they may be generalized seizures or akinetic seizures. Failure of vision comes rapidly and abnormality of the retina is seen early in the disease. The retina shows hypopigmentation with narrowing vessels and brownish decoloration of the macular region followed by optic atrophy. The ERG is always abolished despite patients may have apparent normal fundi. Head circumference is initially normal but becomes microcephalic by the second year. Successive CT or MRI reveal a very rapid progressive cerebral and cerebellar atrophy which is the major feature of the disease. MRI may show hypointense areas of the thalami and questionable hyperintense signals in the periventricular white matter. The EEG is very characteristic showing early and generalized diminution of wave amplitude progressing into an almost isoelectric flattening in the tracing in one or two years. Photostimulation is unremarkable. CSF is normal but occasionally may have an oligoclonal type of gammaglobulin. In peripheral blood azurophilic hypergranulation of neutrophils is present in many patients but there are no vacuolated lymphocytes. Bone marrow is normal. EMG and nerve conduction velocity is normal. By the third year, children are completely vegetative with severe spasticity and exaggerated reflexes. Children usually die by or before seven years of age. Diagnosis is usually made by the combination of rapid progressive flattening of the EEG followed by neuroradiologic imaging which expose progressive brain atrophy and EM evaluation of skin or conjunctival biopsy that reveals typical fine granular osmiophilic lysosomal bodies. Also DNA test studies make the diagnosis. For infantile (CLN1) and classic late-infantile (CLN2) there are now available white cell lysosomal enzyme assays which are both more sensitive and specific for these NCL variants. Also less invasive than a biopsy.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
Diagnosis is usually made by the combination of rapid progressive flattening of the EEG followed by neuroradiologic imaging which expose progressive brain atrophy and EM evaluation of skin or conjunctival biopsy that reveals typical fine granular osmiophilic lysosomal bodies. Also DNA test studies make the diagnosis. In peripheral blood azurophilic hypergranulation of neutrophils is present in many patients but there are no vacuolated lymphocytes. Bone marrow is normal. The EEG is very characteristic showing early and generalized diminution of wave amplitude progressing into an almost isoelectric flattening in the tracing in one or two years. CSF is normal but occasionally may have an oligoclonal type of gammaglobulin. For infantile (CLN1) and classic late-infantile (CLN2) there are now available white
cell lysosomal enzyme assays which are both more sensitive and specific for these
NCL variants. Also less invasive than a biopsy.