Gangliosidosis (GM1) Type I

Lysosomal storage disease. Affected patients have clinical features resembling those of mucopolysaccharidoses types I and VI but without mucopolysacchariduria. Clinical features include joint stiffness, scoliosis, and skeletal dystrophy. Valvular heart diseases are present, of which aortic insufficiency is the most common. Obstructive sleep apnea is frequent, and 50% of reported cases have mild mental retardation.

Caffey Pseudo-Hurler Syndrome; Caffey Syndrome; Hurler-Like Syndrome; Landing Syndrome; Norman-Landing Syndrome; Beta-Galactosidase-1 (GLB 1) Deficiency; Cerebral GM1 Gangliosidosis; Familial Neurovisceral Lipidosis; Generalized Gangliosidosis GM1, Type I; Generalized Infantile Gangliosidosis.

Three forms of gangliosidosis have been described:

• Infantile form: Classic infantile subtype combines the features of a neurolipidosis (i.e., neurodegeneration, macular cherry-red spots) with those of a mucopolysaccharidosis (i.e., visceromegaly, dysostosis multiplex, coarsened facial features). It most frequently presents in early infancy and may be evident at birth.
• Juvenile form: Juvenile subtype is marked by a slightly later age of onset and clinical variability in the classic physical features.
• Adult form: Adult subtype is marked by normal early neurologic development with no physical stigmata and subsequent development of a slowly progressive dementia with parkinsonian features, extrapyramidal disease, and dystonia.

Incidence is estimated at 1:3700 live births in the population of Malta. The incidence in the international general population is unknown.

Autosomal recessive, the gene has been mapped to chromosome 3p21-33.

Ganglioside storage disorder caused by beta-galactosidase deficiency resulting in abnormal accumulation of GM1 ganglioside in the lysosomes of neurons and of oligosaccharides in hepatic, splenic, and other histiocytes and in renal glomerular cells.

Vacuolated lymphocytes in peripheral blood and foam cells in bone marrow; Hurler-like radiographic bone anomalies in infantile form; measurement of enzymatic activity in peripheral leukocytes or fibroblasts.

Infantile form: Symptoms appear shortly after birth and include hypotonia, slow psychomotor development, failure to thrive, feeding difficulty, startle reaction to sounds, and hepatosplenomegaly. Coarse facies with macrocephaly, frontal bossing, full cheeks, and mandibular prognathism. Puffy eyelids, cherry-red macular spots in 50% of patients and occasional corneal opacity. Depressed nasal bridge and prominent philtrum. Macroglossia and enlarged alveolar process. Wide ribs. Hypoplastic ilia and pelvic trabeculation. Short and stubby hands with bullet-shaped phalanges. Flexion contractures of joints and faulty tubulation of long bones. Kyphoscoliosis and short vertebrae in their anteroposterior diameter with convex endplates and hook-like deformities at the thoracolumbar junctions. Cardiomyopathy and paroxysmal supraventricular tachycardia have been described. Severe cerebral degeneration follows, with death in the first 2 years of life, usually as a result of bronchopneumonia. Affected infants often are blind, deaf, and quadriplegic.

Juvenile form: Onset during the second year of life; progressive loss of skills, autistic behavior, ataxia, epilepsy, and spastic paresis develop progressively. Dysostosis multiplex on bone radiograph. Death by around 10 years of age.

Adult-onset form: Onset during childhood or adolescence. Presents as an extrapyramidal disorder with dystonia, dysarthria, and ataxia. No ocular or skeletal anomalies. Dementia may be severe.

Cardiac function should be assessed in light of cardiomyopathic potential. Epileptic history and control factors, including seizure termination, should be ascertained and medications continued where possible. Respiratory function should be checked by chest radiographs and preoperative physiotherapy. Blood tests are necessary because of bone marrow and histiocyte involvement.

Vascular access will likely be difficult because of short, misshapen limbs and contractures with/ without spasticity. In the infantile form, airway management likely will be difficult as in Hurler syndrome: have laryngeal mask airway and nasopharyngeal airway ready for use. Expect face-mask ventilation, direct laryngoscopy, and tracheal intubation to be very difficult; odontoid hypoplasia with possibility of an unstable neck; thickened tracheal wall, necessitating a smaller endotracheal tube than predicted; valvular heart disease. Obstructive sleep apnea. Ventilation could be problematic because of kyphoscoliosis (causing a stiff ribcage), visceromegaly, and bronchopneumonia. The child may be blind, deaf, quadriplegic, and profoundly mentally handicapped, making handling of a difficult anesthetic case even more of a challenge. Choice of anesthetic agents should take the patient's epileptic status into account.

High probability of interaction with epilepsy medications. Avoid anesthetic agents with intrinsic ability to trigger seizure activity.