A severe and fatal form of metachromatic
leukodystrophy that begins around the age of 18 months.
Leukodystrophy Metachromatic; Arylsulfatase A Deficiency;
Greenfield Syndrome; Henneberg Disease; Scholtz Disease;
Scholz-Bielschowsky-Henneberg Syndrome; Greenfield Disease.
Metachromatic Leukodystrophy has a global incidence in
general population of 1:100,000; Scholz-Greenfield syndrome represents
60% of all Metachromatic Leukodystrophy.
Autosomal recessive; arylsulfatase A (ARSA)
gene located at 22q13.31-qter.
Arylsulfatase A is a lysosomal enzyme that
catalyzes the hydrolysis of the 3-O-sulfate linkages of cerebroside sulfate
to form galactocerebroside. The deficiency of this enzyme involves
accumulation of sulfatides, which results in the progressive breakdown of
membranes of the myelin sheath. A small concentration of sulfatide is stored
in the kidneys, gallbladder, and other visceral organs.
Characterized by normal infancy followed by locomotive
disorders between the ages of 12 and 18 months (never walk or difficulty in
walking, hypotonia, weakness, and loss of reflexes). Diagnosis is confirmed
by deficiency of arylsulfatase A activity in leukocytes and cultured skin
fibroblasts. Antenatal diagnosis is possible and a deficiency of enzyme
activity in cultured chorionic villi or amniocytes can be measured.
Death occurs within the first decade of life (2
to 4 years after diagnosis). Clinical features are dominated by neurological
ones (ataxia, spasticity, progressive hypotonia and motor weakness, absent
deep tendon reflexes, peripheral neuropathy with decreased conduction speed,
dysarthria and aphasia, mental regression, dysphagia with bulbar and
pseudobulbar palsies, and myoclonic seizures). Other clinical features concern the
eyes (nystagmus and optic atrophy), digestive organs (gastroesophageal
reflux, excessive salivation, megacolon, undernutrition, gallbladder
dysfunction), orthopedics (frequent genu recurvatum and possibility of hip
dislocation), and muscle anomalies.
Evaluate neurological status
(clinical, full history, MRI, electromyography, EEG, somatosensory evoked potentials) and
digestive function (clinical, pH-metry).
Careful intraoperative positioning is
needed because of nervous and orthopedic impairment. Reflux, dysphagia, and
hypersalivation increase the patient's risk of pulmonary aspiration and require
postoperative care and survey. Particular attention has to be given to
postoperative pain relief because of the potential trigger effect of pain on
seizures. Regional anesthesia is not contraindicated, but nervous
pathological lesion can lead to difficult predictable effects. Benefit has
to be evaluated and explained to patient (if possible) and family.
Antiepileptic treatment must be
maintained until the morning of surgery and interaction with anesthetic drugs must be
considered. Use of preoperative atropine should be recommended to dry
excessive oral secretions. Succinylcholine should probably be avoided
because of muscle anomalies and the risk of hyperkalemic response to the presence of nerve
Nyssen-Van Bogaert Syndrome (van Bogaert-Nyssen-Pfeiffer
Adult form with similar clinical features and the psychiatric presentation of presenile dementia.
Greenfield JGA: A form of progressive cerebral sclerosis in infants
associated with primary degeneration of the interfascicular glia. J Neurol Psychopathol (London) 13:289,
Quader MA, Healy TE: Muscle fibrillation following thiopentone and
pancuronium bromide. An ...