09-02-2004, 05:03 AM
gogi
Sphingolipidoses
1. Tay-Sachs Disease
Presentation is usually at six months of age when affected infants, who previously have appeared normal and passed their early milestones, become lethargic, floppy and poor feeders. They show an abnormal accentuated startle response to sudden noises. There is usually a macular cherry-red spot. Motor development becomes progressively retarded and as the disease progresses blindness, spasticity and decerebrate rigidity occur. Feeding becomes increasingly difficult and death usually occurs by 3 years following pulmonary infection. Later onset forms of the disease with juvenile or adult presentation and sub-acute or chronic courses also occur. In these there may be survival into adolescence, or longer survival with normal intelligence but slowly progressive spinocerebellar degeneration.
Enzyme Test: b-Hexosaminidase A is measured for diagnosis of this disease.
2. Sandhoff Disease
The clinical course of Sandhoff disease is almost identical to that of Tay-Sachs disease except that there may be some extra neurological involvement such as organomegaly and skeletal involvement in the former.
Enzyme Test: b-hexosaminidase (total) is measured for diagnosis of this disease.
3.GM1-Gangliosidosis
GM1-gangliosidosis type I (generalised GM1-gangliosidosis) typically presents within weeks or months of birth with apathy, laboured breathing, feeding difficulties and delay in motor development. Hepatosplenomegaly, a coarse facies and, in some cases, dorsolumbar kyphosis and macular cherry-red spots occur. There is a progressive deteriorating course similar to that in Tay-Sachs disease , with death usually occurring within two years. In the juvenile and adult variants there is a later onset, slower course and less skeletal and visceral involvement.
Enzyme Tests:
Deficiency of lysosomal b -galactosidase activity is the primary defect in GM1-gangliosidosis.
4. Gaucher Disease
This disease is classified into three main types. Type 1 (non-neuronopathic, chronic or adult type) is highly variable in severity, progression and age of onset, which has been reported in the first year and late adult life. Features include splenomegaly, pancytopaenia due to hypersplenism, hepatomegaly and skeletal involvement which may cause mild to severe bone pain, usually in the long bones, and occasionally also pathological fractures. Radiologically there is often aseptic necrosis of the femoral heads, and erosion of the long bones. Pulmonary hypertension and a yellowish-coloured skin occurs in some affected adults. Neurological involvement is typically absent but has been reported in a few cases. Type 2 (acute neuronopathic or infantile type) is a rapidly progressive neurovisceral disease with onset at about six months, severe hepatosplenomegaly and early death before two years. Type 3 (sub-acute neuronopathic or juvenile type) is less rapidly progressive and is characterised by ataxia, myoclonus, seizures and hepatosplenomegaly.
ENZYME TESTS: Deficiency of lysosomal a-glucosidase (glucocerebrosidase) activity is the primary defect. Assay of chitotriosidase is used as an additional test.
5. Krabbe Disease
This disease (also called globoid cell leucodystrophy) has an onset of 3-6 months with vague signs of irritability, hypersensitivity to slight stimuli and some joint stiffness. There is then rapid neurological degeneration with hypertonicity and, later, hypotonicity, blindness and deafness. A peripheral neuropathy is usually present. Symptoms are confined to the nervous system, there being no visceromegaly or skeletal changes. Patients with the classical presentation rarely survive beyond two years, but later onset cases with a more prolonged course are not uncommon.
ENZYME TESTS: Deficiency of galactocerebrosidase is the primary defect
6. Metachromatic Leucodystrophy
This disorder is usually classified into late infantile, juvenile and adult forms. In late infantile MLD the first signs are loss o
Sphingolipidoses
1. Tay-Sachs Disease
Presentation is usually at six months of age when affected infants, who previously have appeared normal and passed their early milestones, become lethargic, floppy and poor feeders. They show an abnormal accentuated startle response to sudden noises. There is usually a macular cherry-red spot. Motor development becomes progressively retarded and as the disease progresses blindness, spasticity and decerebrate rigidity occur. Feeding becomes increasingly difficult and death usually occurs by 3 years following pulmonary infection. Later onset forms of the disease with juvenile or adult presentation and sub-acute or chronic courses also occur. In these there may be survival into adolescence, or longer survival with normal intelligence but slowly progressive spinocerebellar degeneration.
Enzyme Test: b-Hexosaminidase A is measured for diagnosis of this disease.
2. Sandhoff Disease
The clinical course of Sandhoff disease is almost identical to that of Tay-Sachs disease except that there may be some extra neurological involvement such as organomegaly and skeletal involvement in the former.
Enzyme Test: b-hexosaminidase (total) is measured for diagnosis of this disease.
3.GM1-Gangliosidosis
GM1-gangliosidosis type I (generalised GM1-gangliosidosis) typically presents within weeks or months of birth with apathy, laboured breathing, feeding difficulties and delay in motor development. Hepatosplenomegaly, a coarse facies and, in some cases, dorsolumbar kyphosis and macular cherry-red spots occur. There is a progressive deteriorating course similar to that in Tay-Sachs disease , with death usually occurring within two years. In the juvenile and adult variants there is a later onset, slower course and less skeletal and visceral involvement.
Enzyme Tests:
Deficiency of lysosomal b -galactosidase activity is the primary defect in GM1-gangliosidosis.
4. Gaucher Disease
This disease is classified into three main types. Type 1 (non-neuronopathic, chronic or adult type) is highly variable in severity, progression and age of onset, which has been reported in the first year and late adult life. Features include splenomegaly, pancytopaenia due to hypersplenism, hepatomegaly and skeletal involvement which may cause mild to severe bone pain, usually in the long bones, and occasionally also pathological fractures. Radiologically there is often aseptic necrosis of the femoral heads, and erosion of the long bones. Pulmonary hypertension and a yellowish-coloured skin occurs in some affected adults. Neurological involvement is typically absent but has been reported in a few cases. Type 2 (acute neuronopathic or infantile type) is a rapidly progressive neurovisceral disease with onset at about six months, severe hepatosplenomegaly and early death before two years. Type 3 (sub-acute neuronopathic or juvenile type) is less rapidly progressive and is characterised by ataxia, myoclonus, seizures and hepatosplenomegaly.
ENZYME TESTS: Deficiency of lysosomal a-glucosidase (glucocerebrosidase) activity is the primary defect. Assay of chitotriosidase is used as an additional test.
5. Krabbe Disease
This disease (also called globoid cell leucodystrophy) has an onset of 3-6 months with vague signs of irritability, hypersensitivity to slight stimuli and some joint stiffness. There is then rapid neurological degeneration with hypertonicity and, later, hypotonicity, blindness and deafness. A peripheral neuropathy is usually present. Symptoms are confined to the nervous system, there being no visceromegaly or skeletal changes. Patients with the classical presentation rarely survive beyond two years, but later onset cases with a more prolonged course are not uncommon.
ENZYME TESTS: Deficiency of galactocerebrosidase is the primary defect
6. Metachromatic Leucodystrophy
This disorder is usually classified into late infantile, juvenile and adult forms. In late infantile MLD the first signs are loss o