A severe and fatal form of metachromatic leukodystrophy, a lysosomal storage disease, that begins around the age of 18 months.
Leukodystrophy Metachromatic; Arylsulfatase A Deficiency; Greenfield Syndrome; Henneberg Disease; Scholz 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 (2-4 years after diagnosis). Clinical features are dominated by neurological anomalies (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. Intravenous enzyme replacement therapy is able to control mostly the damage of visceral organs but cannot prevent nervous impairment.
Precautions before anesthesia
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 ...