MPS-like disease presumably caused by VPS16-associated impairment of intracellular trafficking
Jan-Christoph Schoene-Bake, Tobias Haack, Eva Bueltmann, Anibh Martin Das, Hans Hartmann
Objectives Disorders of intracellular trafficking are rare and frequently result in multisystem-involvement depending on the affected pathways. Few patients with clinical features of mucopolysaccharidosis (MPS) due to genetic variants affecting intracellular trafficking pathways such as HOPS, CORVET, CHEVI have been described. Recently, four patients with MPS-like phenotype due to variants in the VPS16 gene have been published.
Case Report The now 15-year-old adolescent was born SGA. Anemia was observed at the age of 6 months and global developmental delay noted in the first year of life. Coarse facial features and short stature suggested the diagnosis of MPS. Metabolic testing showed an increased excretion of glycosaminoglycans, mucopolysaccharides and neuraminic acid in urine, however enzyme-analysis was unrevealing. Further genetic analyses (chromosomes, ArrayCGH, RASopathy genes) were normal. In the second decade, the boy showed a neurodegenerative phenotype with loss of ambulation and expressive language and developed neuropathy. Neutropenia was noted and GCSF treatment started at 13 years. 3T-MRI of the brain revealed a reduced white matter volume and iron accumulation in the basalganglia. Using Trio Exome sequencing, the missense variant of unknown significance c.540G>T; p.Trp180Cys in the VPS16 gene was found, further functional analyses are under way.
Conclusion We report the up to now oldest patient with an MPS-like phenotype presumably due to changes in the VPS16 gene extending the differential diagnoses of MPS. This case highlights the need for further diagnostics such as whole exome or genome sequencing in patients with clinical and laboratory signs but normal enzyme activities for MPS.
Keywords: MPS, intracellular traficking, VPS16, mucopolysaccharidosis
Jan-Christoph Schoene-Bake
Medizinische Hochschule Hannover
Germany
Tobias Haack
University of Tuebingen
Germany
Eva Bueltmann
Medizinische Hochschule Hannover
Germany
Anibh Martin Das
Medizinische Hochschule Hannover
Germany
Hans Hartmann
Medizinische Hochschule Hannover
Germany
Objectives Disorders of intracellular trafficking are rare and frequently result in multisystem-involvement depending on the affected pathways. Few patients with clinical features of mucopolysaccharidosis (MPS) due to genetic variants affecting intracellular trafficking pathways such as HOPS, CORVET, CHEVI have been described. Recently, four patients with MPS-like phenotype due to variants in the VPS16 gene have been published.
Case Report The now 15-year-old adolescent was born SGA. Anemia was observed at the age of 6 months and global developmental delay noted in the first year of life. Coarse facial features and short stature suggested the diagnosis of MPS. Metabolic testing showed an increased excretion of glycosaminoglycans, mucopolysaccharides and neuraminic acid in urine, however enzyme-analysis was unrevealing. Further genetic analyses (chromosomes, ArrayCGH, RASopathy genes) were normal. In the second decade, the boy showed a neurodegenerative phenotype with loss of ambulation and expressive language and developed neuropathy. Neutropenia was noted and GCSF treatment started at 13 years. 3T-MRI of the brain revealed a reduced white matter volume and iron accumulation in the basalganglia. Using Trio Exome sequencing, the missense variant of unknown significance c.540G>T; p.Trp180Cys in the VPS16 gene was found, further functional analyses are under way.
Conclusion We report the up to now oldest patient with an MPS-like phenotype presumably due to changes in the VPS16 gene extending the differential diagnoses of MPS. This case highlights the need for further diagnostics such as whole exome or genome sequencing in patients with clinical and laboratory signs but normal enzyme activities for MPS.
Keywords: MPS, intracellular traficking, VPS16, mucopolysaccharidosis
Jan-Christoph Schoene-Bake
Medizinische Hochschule Hannover
Germany
Tobias Haack
University of Tuebingen
Germany
Eva Bueltmann
Medizinische Hochschule Hannover
Germany
Anibh Martin Das
Medizinische Hochschule Hannover
Germany
Hans Hartmann
Medizinische Hochschule Hannover
Germany
Jan-Christoph Schoene-Bake
Medizinische Hochschule Hannover Germany
Medizinische Hochschule Hannover Germany