MUCOPOLYSACCHARIDOSIS IN A THREE MONTHS OLD INFANT Clinical and Ultrastructural Studies

A mucopolysaccharidosis is diagnosed in an infant aged 3 months. Clinical and X-ray data are not typical, while biological studies reveal an increased mucopolysacchariduria affecting both heparan and dermatan sulfate. Study of lysosomal hydrolases in the liver discloses a normal activity of β-galactosidase. Hepatic ultrastructure shows, in both parenchymal and Kupffer cells, the presence of clear inclusions analoguous to those found in typical mucopolysaccharidoses, although more numerous and generally smaller.     

Subcortical infarction in a young adult with Hunter syndrome

IntroductionHunter syndrome (mucopolysaccharidosis type II, MPS II) is an X-linked lysosomal storage disease caused by deficiency of iduronate-2-sulfatase. Recently, stroke caused by embolization with Hunter syndrome has been reported. Here, we report the case of a 23-year-old Japanese man with Hunter syndrome who developed subcortical infarction by the mechanism similar to branch atheromatous disease (BAD).Case presentationHe had been treated with idursulfase supplementation. He presented with left-sided weakness and conjugate eye deviation to the right, and was diagnosed with branch atheromatous disease affecting the right corona radiata, based on MRI findings. The patient was treated with argatroban and aspirin. Magnetic resonance angiography demonstrated no evidence of luminal narrowing of the cerebral arteries. T1-sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) imaging revealed thickened middle cerebral artery. The patient had markedly low flow-mediated vasodilation, suggesting impaired vasodilation in response to nitric monoxide.ConclusionThe arterial wall thickening and impaired vasodilation in the cerebral arteries related to subcortical infarction. We should clarify the mechanism of cerebral infarction in Hunter syndrome patients.     

Cerebrospinal fluid shunts in the management of behavioural problems in Sanfilippo syndrome (MPS III)

Severe behavioural disturbance is a very common feature of Sanfilippo syndrome (mucopolysaccharidosis III, MPSIII), and one of the more difficult aspects of the disease to treat. We describe a series of six patients with MPS III who had cerebrospinal shunts inserted in an attempt to ameliorate behaviour that had proved refractory to conventional treatment. Symptoms improved significantly in all six but removal of the shunt was necessitated in one patient due to shunt blockage and infection. Conclusion Our experience suggests cerebrospinal fluid shunting should be formally evaluated as an adjunct to conventional forms of treatment of extreme behavioural disturbance in MPS III. Received: 14 October 1997 / Accepted: 25 February 1998     

Sanfilippo Type C Syndrome in Two Sisters

ABSTRACT. Two sisters are described with mucopolysaccharidosis (MPS) Sanfilippo type C syndrome. This diagnosis is emphasized to be easily overlooked due to subtile clinical and radiological deviations, but should be considered in any case of unspecific progressive mental retardation, especially when sleep disturbance, aggressivity and hyperactivity are prominent symptoms.     

Lysosomal storage of sulfated glycosaminoglycans induced by two bis-aminomethyl anthrachinones

 Several immunomodulatory drugs, all of them symmetrically substituted dicationic amphiphilic compounds, are known to cause lysosomal storage of sulfated glycosaminoglycans (GAGs) in intact animals and cultured fibroblasts. The storage is due to impaired GAG degradation. The standard compound is tilorone (2,7-bis[2-(diethylamino)ethoxy]fluoren-9-one). In the present study two bis-aminomethyl anthrachinones were examined for their ability to induce lysosomal GAG storage in cultured bovine corneal fibroblasts. For reference, a bis-aminoethoxy-anthrachinone compound (RMI-10.024) was included, which is known to be a potent inducer of lysosomal GAG storage. The present morphological, radiochemical, and biochemical results show that the bis-aminomethyl anthrachinone compounds investigated cause lysosomal storage of GAGs, although with significantly lower potencies than the bis-aminoethoxy anthrachinone. Dermatan sulfate contributed approximately 90% to the drug-induced increment of intracellular GAGs. The present results suggest that the length of the side chains, i. e., the distance between the aromatic ring system and the protonizable nitrogen of the side chains, and the position of the side chains relative to the aromatic ring system are important molecular features influencing the potency of inducing lysosomal GAG storage. Received: 14 July 1995 / Accepted: 17 October 1995     

Nocturnal frontal lobe epilepsy in mucopolysaccharidosis

Nocturnal frontal lobe epilepsy (NFLE) is an epileptic syndrome that is primarily characterized by seizures with motor signs occurring almost exclusively during sleep. We describe 2 children with mucopolysaccharidosis (MPS) who were referred for significant sleep disturbance. Long term video-EEG monitoring (LT-VEEGM) demonstrated sleep-related hypermotor seizures consistent with NFLE.     

Restricted joint range of motion in patients with MPS II: correlation with height, age and functional status

Aim: The aims of the study were to assess shoulder range of motion (ROM) in patients with mucopolysaccharidosis type II (MPS II) and to correlate joint mobility with patients’ height, age and functional status. Methods: Passive ROM and Z‐score of height were followed in 29 patients with MPS II (mean age 11.5 years, range 2–29 years) between the years 2005 and 2010. Passive ROM was measured by a goniometer, and height, by a stadiometer. Functional status was assessed by an age‐appropriate health assessment questionnaire (HAQ). Results: (i) A strong correlation was observed between patients’ age and Z‐score of patients’ height (R = 0.78, p < 0.001). (ii) A medium correlation was observed between Z‐score of patients’ height and passive shoulder flexion and abduction (R = 0.697, p < 0.001 and R = 0.63, p < 0.001, respectively). The progression of restriction was slower in attenuated patients. (iii) Restrictions in shoulder flexion and abduction were already observed before the second year of life. (iv) ROM limitations intensified and became more severe with age. (v) Activities of daily living depended on cognitive impairment of patients with MPS II. Conclusion: Range of motion limitations in patients with MPS II correlate with patients’ height, increase with patients’ age and are more pronounced in a severe form of MPS II.     

Structural and clinical implications of amino acid substitutions in N-acetylgalactosamine-4-sulfatase: insight into mucopolysaccharidosis type VI

To elucidate the basis of mucopolysaccharidosis type VI (MPS VI) from the point of view of enzyme structure, we built structural models of mutant N-acetylgalactosamine-4-sulfatase (4S) resulting from 34 missense mutations (17 severe and 17 attenuated), and analyzed the influence of each amino acid replacement on the structure by calculating the number of atoms affected. Then, we calculated the average of solvent-accessible surface area value of the residues for which a substitution was identified in the severe MPS VI group and compared it with that in the attenuated MPS VI group. In the severe MPS VI group, the number of atoms influenced by a mutation was generally larger than that in the attenuated MPS VI group in both the main chain and the side chain, and residues associated with the mutations found in the severe MPS VI group tended to be less solvent-accessible than those in the attenuated MPS VI group. Furthermore, we analyzed the structural changes in 4S caused by six amino acid substitutions, for which the expressed proteins have been characterized, by means of color imaging. The results revealed that R95Q, G144R, H393P, and C521Y cause large structural changes, and that they are associated with the severe phenotype. On the other hand, G137V and Y210C are thought to cause small structural changes in a limited region resulting in the attenuated phenotype. Structural study is useful for elucidating the basis of MPS VI and predicting the influence of amino acid substitutions on clinical outcome, although there are a couple of exceptional cases.