Neuroaxonal dystrophy. Infantile form. Seitelberger disease.
Incidence
This condition is an autosomal recessive disorder of unknown origin with no ethnic prevalence.
Clinical Characteristics
Symptoms begin in the second year of life with progressive difficulties in walking but may start earlier in the second semester of the first year with psychomotor regression. Hypotonia may be striking. Pyramidal signs, loss of deep tendon reflexes with an EMG showing partial denervation atrophy and normal nerve conduction velocity is characteristic, associated with progressive optic atrophy, normal CSF and cerebellar atrophy revealed by MRI. Pathologically is characterized by multiple widespread swelling of axons and presynaptic terminals with typical ultrastructural features and degeneration of neurons in the pallidum and cerebellum. The detection of typical ultrastructural changes in peripheral nerve biopsy is necessary for diagnosis. Age of onset is usually between 14 and 18 months, rarely up to 3 to 4 years. Sometimes as early as six months. Development of CNS is normal at first or delayed. Most children never achieve complete independent locomotion. The first reliable sign is a slowly increasing difficulty in walking. There is a tendency to fall and occasionally unsteadiness of gait. With earlier onset, children exhibit gradual regression of all motor functions including standing and sitting and lack of spontaneous activity. Hypotonia in this cases is very obvious. Physical examination show lower limbs either spastic or hypotonic, sometimes suggesting neuromuscular disorder. Later pyramidal signs are present. Deep tendon reflexes may be exaggerated but usually are unobtainable on the beginning especially in cases of early onset. If present, they become absent as the disease progress. Sometimes, diminish sensibility to pain in lower extremities has been reported. EMG show denervation potentials distally but motor and sensory nerve conduction velocities are normal. Blindness with optic atrophy is practically a constant finding. The interval between the onset of disease and optic atrophy varies from ten months to two years. Pendular nystagmus and non-paralytic squint may precede evident failure of vision and may start early. Athetosis and other extrapyramidal signs are not part of the clinical picture but involuntary movements of face and hands occasionally are seen late in the disease. Seizures are rare. EEG show high amplitude fast activity. There is progressive mental deterioration together with the beginning of the motor signs. Speech is never obtained or is very limited. Spinal fluid is normal. The head circumference is normal or mildly reduced. Duration of the disease range from three to eight years. There is no known biochemical abnormalities. The most valuable diagnostic test is the finding of typical ultrastructural axonal alteration in biopsies of skin or conjunctiva. The typical pathological findings are large (50 microns) eosinophilic spheroids often of concentric pattern. They are seen in both central and peripheral nervous system. They represent axonal swellings. Under the electron microscopy, the spheroids and the eosinophilic bodies are composed of aggregates of smooth membrane in tubules which are characteristic. There are abnormal visual and somatosensory evoked potentials and cerebellar atrophy on MRI. Abnormal EMG with denervation atrophy but normal motor and sensory nerve conduction velocity and normal CSF. Definite diagnosis rest in the demonstration of EM typical intraaxonal membranous aggregates in the distal part of peripheral nerves or at the neuromuscular junction in biopsy specimens of the sural nerve. DNA analysis is not available yet.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
The detection of typical ultrastructural changes in peripheral nerve biopsy is necessary for diagnosis. There is no known biochemical abnormalities. The most valuable diagnostic test is the finding of typical ultrastructural axonal alteration in biopsies of skin or conjunctiva. The typical pathological findings are large (50 microns) eosinophilic spheroids often of concentric pattern. They are seen in both central and peripheral nervous system. They represent axonal swellings. Under the electron microscopy, the spheroids and the eosinophilic bodies are composed of aggregates of smooth membrane in tubules which are characteristic. There are abnormal visual and somatosensory evoked potentials and cerebellar atrophy on MRI. Definite diagnosis rest in the demonstration of EM typical intraaxonal membranous aggregates in the distal part of peripheral nerves or at the neuromuscular junction in biopsy specimens of the sural nerve. DNA analysis is not available yet.