NeurometPlus

Incidence

This is an autosomal recessive disorder. There is accumulation of GM1 gangliosides in nerve cells and galactosyl- oligosacharides and keratan sulfate degradation products in other tissues.

Clinical Characteristics

This is a disease that is observed since the newborn period, manifesting with diminished spontaneous activity and hypotonia since first weeks of life. Head control may be acquired but sitting posture is never obtained. The main features of this condition are: severe cerebral degeneration leading to death within the first two years of life. Also, the presence of skeletal deformities resembling Hurler disease. The main clinical characteristic of these patients are dwarfism and death in infancy, hypertrichosis on the skin, coarse facies, full forehead and flat nose, wide spaced eyes, clear cornea and cherry red spots in half of the patients. Many infants have facial and peripheral edema in the first weeks of life. After a few months, visual failure appear frequently showing a pendular nystagmus. Macular cherry red spots is observed in 60 % of cases and often is not seen until age 6 months. Seizures may occur generally during the late stages of the disease. With time, hypotonia gives way to spasticity with tonic spasms and pyramidal signs. Head size is initially normal but later it become small or microcephalic. There are gingival hyperplasia, short neck, hepatomegaly and splenomegaly with inguinal hernia. Kyphosis and scoliosis, thick ribs, joint stiffness, mental retardation and cerebral degeneration, angiokeratoma corporis diffusum on skin. X-rays shows hypoplastic vertebrae bodies with beaked vertebral bodies. Clinically, the disease is expressed by early psychomotor deterioration, macular cherry red spots, facial dysmorphism, bone deformities, and hepatomegaly. Vacuolated lymphocytes are found in blood and foamy histiocytes in bone marrow smears. Galactose-containing oligosacharides and keratan sulfate are excreted in the urine. There is accumulation of gangliosides in neurons and in hepatic, splenic and other histiocytes and in renal glomerular epithelium. Sometimes, the developmental delay neurologically becomes evident somewhat later during the third to sixth months of life. This is associated almost always with feeding difficulties and failure to thrive. Peripheral nerves are normal. Spinal fluid is normal. If child survives above twelve months, they behave with decerebrate rigidity. They usually die by the age of two years due to pneumonia. The clinical characteristic that suggests this condition are usually non neurologic. These patients have special facial features, skeletal changes, hematologic abnormalities and oligosachariduria. Hepatomegaly and later splenomegaly are usually present after six months. Dysmorphic features may be striking. They may already be present at birth but become more apparent with time. The dysmorphism include wide depressed nasal bridge, frontal bossing, epicantal folds, elongated upper lip, gingival hypertrophy or thickenned alveolar ridge, puffy eyelids, moderate macroglossia, low set ears and short jaw. There is limited mobility with flexion contractures at the joints and after a few months, lumbodorsal kypho-scoliosis may develop. The most important radiologic signs are in the long bones and spine and they are constant and necessary for the clinical diagnosis. There is marked subperiosteal bone formation as an early sign and it may be present since birth. Later there is widening of the diaphyses of bones and other bone changes. Hypoplasia and beaking of one or more vertebrae at the thoracolumbar junction is characteristic but become evident after six months of age. These deformities are similar to the mucopolysacharidosis (dysostosis multiplex). From 10 to 80 % of lymphocytes in blood are vacuolated. Also, there is a finely vacuolated foamy histiocytes in bone marrow with glomerular epithelial citoplasmic vacuolization, galactose-containing oligosacharides and moderate increase in keratan sulfate is found in urine. Occasionally the heart may be enlarged and heart failure has been reported due to endocardial fibroelastosis and thickening of the valves. Occasionally, corneal opacity and exagerated acousticomotor response has been seen in some patients. The diagnosis is made by measurement of acid beta-galactosidase activity in leukocytes and cultured fibroblasts. Urine oligosacharides analysis is helpful. Neurons in the central and autonomic nervous system are packed with intracitoplasmic granular material that on the EM are shown to be intralysosomal membranous cytoplasmic bodies resembling those seen in Tay-Sachs histiocytes and many viscera and many other cells are distended with large lysosomes. There is no treatment available, only symptomatic treatment. Laboratory testing: there is no mucopolisacariduria, there are vacuolar lymphocytes and there is beta-galactosidase deficiency.

Precipitants

no

Provocation Tests

no

Diagnostic Procedures

EB-W, EB-F. Galactose-containing oligosacharides and keratan sulfate are excreted in the urine. From 10 to 80 % of lymphocytes in blood are vacuolated. Also, there is a finely vacuolated foamy histiocytes in bone marrow with glomerular epithelial citoplasmic vacuolization, galactose-containing oligosacharides and moderate increase in keratan sulfate is found in urine.The diagnosis is made by measurement of acid beta-galactosidase activity in leukocytes and cultured fibroblasts. Urine oligosacharides analysis is helpful.