TY  - JOUR
A1  - Lorenz, Delia
A1  - Musacchio, Thomas
A1  - Kunstmann, Erdmute
A1  - Grauer, Eva
A1  - Pluta, Natalie
A1  - Stock, Annika
A1  - Speer, Christian P.
A1  - Hebestreit, Helge
T1  - A case report of Sanfilippo syndrome - the long way to diagnosis
JF  - BMC Neurology
N2  - Background
Mucopolysaccharidosis type III (Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in the heparan-N-sulfatase enzyme involved in the catabolism of the glycosaminoglycan heparan sulfate. It is characterized by early nonspecific neuropsychiatric symptoms, followed by progressive neurocognitive impairment in combination with only mild somatic features. In this patient group with a broad clinical spectrum a significant genotype-phenotype correlation with some mutations leading to a slower progressive, attenuated course has been demonstrated.
Case presentation
Our patient had complications in the neonatal period and was diagnosed with Mucopolysaccharidosis IIIa only at the age of 28 years. He was compound heterozygous for the variants p.R245H and p.S298P, the latter having been shown to lead to a significantly milder phenotype.
Conclusions
The diagnostic delay is even more prolonged in this patient population with comorbidities and a slowly progressive course of the disease.
KW  - Mucopolysaccharidosis IIIa
KW  - diagnostic delay
KW  - genotype-phenotype correlation
KW  - p.S298P
KW  - p.R245H
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300465
VL  - 22
IS  - 1
ER  - 
TY  - JOUR
A1  - Wagenhäuser, Laura
A1  - Rickert, Vanessa
A1  - Sommer, Claudia
A1  - Wanner, Christoph
A1  - Nordbeck, Peter
A1  - Rost, Simone
A1  - Üçeyler, Nurcan
T1  - X-chromosomal inactivation patterns in women with Fabry disease
JF  - Molecular Genetics & Genomic Medicine
N2  - Background

Although Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA), women may develop severe symptoms. We investigated X-chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women.
Patients and Methods

We included 95 women with mutations in GLA (n = 18 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation status of the androgen receptor gene. The mutated X-chromosome was identified by comparison of samples from relatives. Patients underwent genotype categorization and deep clinical phenotyping of symptom severity.
Results

43/95 (45%) women carried mutations categorized as classic. The XCI pattern was skewed (i.e., ≥75:25% distribution) in 6/87 (7%) mouth epithelial cell samples, 31/88 (35%) blood samples, and 9/27 (33%) skin fibroblast samples. Clinical phenotype, α-galactosidase A (GAL) activity, and lyso-Gb3 levels did not show intergroup differences when stratified for X-chromosomal skewing and activity status of the mutated X-chromosome.
Conclusions

X-inactivation patterns alone do not reliably reflect the clinical phenotype of women with FD when investigated in biomaterial not directly affected by FD. However, while XCI patterns may vary between tissues, blood frequently shows skewing of XCI patterns.
KW  - Fabry disease
KW  - Fabry genotype
KW  - Fabry phenotype
KW  - female Fabry patients
KW  - X-chromosomal inactivation
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312795
VL  - 10
IS  - 9
ER  -