ABSTRACT
BACKGROUND: Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is an X-linked recessive lysosomal storage disorder resulting from deficient activity of iduronate 2-sulfatase (IDS) and the progressive lysosomal accumulation of sulfated glycosaminoglycans (GAGs). METHODS: A diagnosis of MPS II or Hunter syndrome was performed based on the following approach after a clinical and paraclinical suspicion. Two biochemical and molecular tests were carried out separately and according to the availability of the biological material. RESULTS: All patients in this cohort presented the most common MPS II clinical features. Electrophoresis of GAGs on a cellulose acetate plate in the presence of a high concentration of heparane sulfate showed an abnormal dermatan sulfate band in the patients compared with that in a control case. Furthermore, leukocyte IDS activity ranged from 0.00 to 0.75 nmol/h/mg of leukocyte protein in patients. Five previously reported mutations were identified in this study patients: one splice site mutation, c.240 + 1G > A; two missense mutations, p.R88P and p.G94D; a large deletion of exon 1 to exon 7; and one nonsense mutation, p.Q396*. In addition, two novel alterations were identified in the MPS II patients: one frame shift mutation, p.D450Nfs*95 and one nonsense mutation, p.Q204*. Additionally, five known IDS polymorphisms were identified in the patients: c.419-16 delT, c.641C > T (p.T214M), c.438 C > T (p.T146T), c.709-87G > A, and c.1006 + 38 T > C. CONCLUSIONS: The high level of urine GAGs and the deficiency of iduronate 2-sulfatase activity was associated with the phenotype expression of Hunter syndrome. Molecular testing was useful for the patients' phenotypic classification and the detection of carriers.
Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , Glycoproteins/genetics , Mucopolysaccharidosis II/diagnosis , Mucopolysaccharidosis II/genetics , Mutation , Adolescent , Adult , Child , Child, Preschool , DNA Mutational Analysis , Enzyme Activation , Female , Genetic Association Studies/methods , Glycosaminoglycans/metabolism , Glycosaminoglycans/urine , Humans , Infant , Male , Mucopolysaccharidosis II/epidemiology , Mucopolysaccharidosis II/metabolism , Phenotype , Tunisia/epidemiology , Young AdultABSTRACT
PURPOSE: To describe the management of infants with epileptic spasms (ESs) in a low-income country and identify factors predictive of their prognosis. MATERIAL AND METHODS: We conducted a retrospective study in a university hospital in Tunis, Tunisia, over a period of 10 years. We included infants with recurrent ESs. RESULTS: Thirty-eight patients were included. The median age at onset of ESs was 5 months. Typical hypsarrhythmia was found in 21 patients (55%). Brain MRI was done in 32 patients (84%) and metabolic work-up in 34 patients (89%). ESs were categorized as symptomatic in 58% of the patients. Vigabatrin was prescribed as the first-line drug in almost half of the patients. At the last follow-up, 63% of the patients were seizure-free and 82% had a psychomotor delay. The presence of other types of seizures was associated with uncontrolled epilepsy at the last follow-up (P=0.020). The persistence of spasms after the first-line treatment was associated with abnormal final psychomotor development (P=0.047). CONCLUSIONS: Investigation practices and final outcomes of our patients were comparable to data from high-income countries. Treatment practices have been standardized to be in line with international guidelines.