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
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
- 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
Incidence is estimated at 1:3700 live births in the
population of Malta. The incidence in the international general population
Autosomal recessive, the gene has been mapped to
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
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
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 ...