Are GMI gangliosidosis and Morquio type B two different disorders or part of one phenotypic spectrum?

Abstract

Monosialotetrahexosylganglioside (GMI) gangliosidosis and Morquio type B (MorB) are two lysosomal storage disorders (LSDs) caused by the same enzyme deficiency, β‐galactosidase (βgal). GMI gangliosidosis, associated with GMI ganglioside accumulation, is a neurodegenerative condition characterized by psychomotor regression, visceromegaly, cherry red spot, and facial and skeletal abnormalities. MorB is characterized by prominent and severe skeletal deformities due to keratan sulfate (KS) accumulation. There are only a few reports on intermediate phenotypes between GMI gangliosidosis and MorB. The presentation of two new patients with this rare intermediate phenotype motivated us to review the literature, to study differences and similarities between GMI gangliosidosis and MorB, and to speculate about the possible mechanisms that may contribute to the differences in clinical presentation. In conclusion, we hypothesize that GMI gangliosidosis and MorB are part of one phenotypic spectrum of the same disease and that the classification of LSDs might need to be revised.

Morquio B disease: a case report

“…MBD is a rare autosomal recessive disorder that significantly affects the musculoskeletal system ( 1 , 2 ). As seen in this patient, the diagnosis of MBD is typically made around the age of 4–8 years following the appearance of skeletal abnormalities such as short height and lower extremity weakness ( 1 , 2 ).…”

“…Mucopolysaccharidosis IV type B, or Morquio B disease (MBD), is a rare autosomal recessive lysosomal storage disorder that occurs due to mutations in the genes encoding for β-galactosidase enzyme ( 1 , 2 ). Deficiency in the enzymatic activity of β-galactosidase causes abnormal accumulation of glycosaminoglycans such as keratan sulfate ( 1 , 2 ). This buildup can occur in the cornea, urine, and cartilage, where it causes abnormal endochondral ossification and bone growth.…”

“…Orthopedic treatment provides symptomatic relief; however, it does not halt disease progression, leading to continual skeletal issues and pain for patients. MBD patients are at higher risk for death due to complications arising from valvular heart disease and respiratory failure, as well as spinal cord injury due to spinal cord compression and vertebral instability ( 1 , 2 ).…”

Congenital Heart Malformations Masked by Infantile Gangliosidosis—Case Report and Growing Evidence for Metabolic Disease-Associated Aortopathies

“…In total, two diseases have been linked to GLB1 mutations: Gangliosidosis type I (GM1) and Morquio type B (MBD). The former is caused by monosialotetrahexosylganglioside (GM1) accumulation in the brain and other organs, while the latter is a consequence of glycosamino-glycan (GAG) and keratan sulfate (KS) excess accumulation in bones, cartilage, and cornea [ 3 ]. Besides Morquio type B, gangliosidosis should be differentiated from mucopolysaccharidoses, other sphingolipidoses, and glycoproteinoses [ 4 ] ( Table 1 ).…”

“…Recent research indicates that Morquio type B and GMI are part of the spectrum of the same condition, and that the severity of the manifestations as well as overlapping cases is due to the localization of the GLB1 gene mutation as well as the type of mutation [ 3 ]. The reported incidence for GM1 is 1:100,000–1:200,000 live births.…”