NeurometPlus

Incidence

It is an autosomal recessive multisystem disease. Some 250 patients have been reported, usually from Northern Europe and Japan. There are abnormal carbohydrate deficient glycoproteins, particularly transferine. The gene is located in chromosome #16.

Clinical Characteristics

This condition usually manifests in the first year of life with marked developmental delay with failure to thrive, hypotonia, feeding problems. There is poor or absent ocular fixation. Non paralytic strabismus is present frequently. Unexplained depression of consciousness sometimes preceded by fever. Rhythmic head movements and respiratory difficulty has been reported. There are fat pads and areas of atrophic skin on buttocks and arms and often there are inverted nipples but not always present. Moderate hepatomegaly and elevated liver enzymes occur. Cardiac insufficiency with pericardial effusion is reported. Most patients survive infancy. Patients almost never walk despite reaching adolescence. There is atrophy and weakness of lower extremities with peripheral neuropathy (absent DTR's and decreased NCV), cerebellar ataxia, pigmentary degeneration of the retina, severe mental retardation with IQ's between 40 and 60. This IQ is usually static. There are no behavioral problems. Scoliosis and thoracic deformities are noted with FTT. There may be a peculiar face with a large nose and ears. Hypogonadism is present in adulthood. The patient's symptoms are usually of an acute encephalopathy or a stroke like episodes that usually fully recover. There are alternating areas of lipohyperplasia and lipoatrophy may occur in the thighs. The liver and heart problems resolve in the first three to four years but central nervous system problems remains, mainly gross motor disability with ataxia, dyskinesia, seizures. With age, there is progressive flexion contractures. CSF protein tends to be high. Osteoporosis tends to occur late. MRI shows striking cerebellar atrophy with atrophy of the pons (oligopontocerebellar atrophy). CT scan may show diffuse calcification of white matter. The intermittent crisis of depression of consciousness and stroke-like symptoms are infection-triggered. Patient may have chronic diarrhea. Diagnosis is made by low levels of thyroxine-binding protein. There is abnormal proportion of disialotransferin and asialotransferin, replacing the normal tetrasialotransferin in serum and CSF. It may be low levels of sialic acid, galactose and N-acetylglucosamine.

Precipitants

Infections may trigger the acute episode of depression of consciousness and stroke-like syndrome.

Provocation Tests

no

Diagnostic Procedures

Diagnosis is made by low levels of thyroxine-binding protein. There is abnormal proportion of disialotransferin and asialotransferin, replacing the normal tetrasialotransferin in serum and CSF. It may be low levels of sialic acid, galactose and N-acetylglucosamine.