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At a glance

Gangliosidosis is a subcategory of sphingolipidosis defined by the storage of two different types of lipid leading to the accumulation of lipids known as gangliosides. Lysosomal storage disease. There are two distinct genetic causes (Types I and II) of the disease. Both are autosomal recessive and affect males and females equally. Affected patients have clinical features resembling those of mucopolysaccharidoses Type I (Hurler Syndrome, Scheie Syndrome, and Hurler-Scheie Syndrome) and VI (Maroteaux-Lamy Syndrome), however 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.

Synonyms

Caffey Pseudo-Hurler Syndrome; Caffey Syndrome; Hurler-Like Syndrome; Landing Syndrome; Norman-Landing Syndrome; Beta-Galactosidase-1 (GLB1) Deficiency; Cerebral GM1 Gangliosidosis; Familial Neurovisceral Lipidosis; Generalized Gangliosidosis GM1, Type I; Generalized Infantile Gangliosidosis.

Classification

Three forms of gangliosidosis have been described:

  • Infantile Form: Classic infantile subtype combines the features of a neurolipidosis (ie, neurodegeneration, macular cherry-red spots) with those of a mucopolysaccharidosis (ie, 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

Incidence is estimated at 1:3,700 live births in the population of Malta. The incidence in the international general population is unknown.

Genetic inheritance

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

Pathophysiology

Ganglioside storage disorder caused by betagalactosidase 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.

Diagnosis

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.

Clinical aspects

  • 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. Physical characteristics include puffy eyelid, cherry-red macular spots in 50% of patients, occasional corneal opacity, depressed nasal bridge, and prominent philtrum. Macroglossia and enlarged alveolar process can also be present. Wide ribs, hypoplastic ilia and pelvic trabeculation, short and stubby hands with bullet-shaped phalanges are present. Flexion contractures of joints and faulty tubulation of long bones, kyphoscoliosis and short vertebrae ...

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