Short Communication Impact of early enzyme-replacement therapy for mucopolysaccharidosis VI: results of a long-term follow-up of Brazilian siblings.

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive multisystem lysosomal storage disorder, which is characterized by the deficiency of the enzyme arylsulfatase B encoded by the ARSB gene. Treatment of this disease with enzyme-replacement therapy (ERT) improves the clinical status of and generates hope for MPS VI patients. However, only few reports on patients with MPS VI treated before 5 years of age have been published. Thus, the objective of this study was to compare the clinical parameters of two sisters affected by MPS VI who started ERT at different ages (9 years and 1 year 5 months, respectively) and to determine the most relevant clinical impacts of early treatment after 85 months of evaluation. The treatment was well tolerated by both siblings. ERT in the younger sibling resulted in increased growth, an improved 6-minute walk test, less coarse face, slower progression of cardiac valve disease, and the absence of compressive myelopathy compared to that in her older sister. On the other hand, the older sibling had typical MPS VI phenotypic features before the commencement of ERT. Corneal clouding, clawed hands, and progressive skeletal changes were observed in both siblings despite the treatment. Both siblings displayed reduced frequencies of upper respiratory infections and apnea indices. This study emphasizes that early diagnosis and treatment of MPS VI are critical for a better disease outcome and to enhance the quality of life for these patients.

Subclinical left ventricular dysfunction in childhood-onset systemic lupus erythematosus: a two-dimensional speckle-tracking echocardiographic study.

OBJECTIVES: The main purpose of the study was to investigate left ventricular (LV) subclinical systolic and diastolic dysfunction in childhood-onset systemic lupus erythematosus (c-SLE) patients using two-dimensional speckle-tracking (2DST) echocardiography. We also interrogated possible correlations between impairment of myocardial deformation and the SLE Disease Activity Index 2000 (SLEDAI-2K), as well as the presence of traditional and disease-related cardiovascular risk factors (CRFs). METHOD: A total of 50 asymptomatic patients and 50 controls (age 14.74 vs. 14.82 years, p = 0.83) were evaluated by standard and 2DST echocardiography. RESULTS: Despite a normal ejection fraction (EF), there was reduction in all parameters of LV longitudinal and radial deformation in patients compared to controls: peak longitudinal systolic strain (PLSS) [-20.3 (-11 to -26) vs. -22 (-17.8 to -30.4)%, p < 0.0001], PLSS rate [-1.19 ± 0.21 vs. -1.3 ± 0.25 s(-1), p = 0.0005], longitudinal strain rate in early diastole [1.7 (0.99-2.95) vs. 2 (1.08-3.00) s(-1), p = 0.0034], peak radial systolic strain [33.09 ± 8.6 vs. 44.36 ± 8.72%, p < 0.0001], peak radial systolic strain rate [1.98 ± 0.53 vs. 2.49 ± 0.68 s(-1), p < 0.0001], and radial strain rate in early diastole [-2.31 ± 0.88 vs. -2.75 ± 0.97 s(-1), p = 0.02]. Peak circumferential systolic strain [-23.67 ± 3.46 vs. -24.6 ± 2.86%, p = 0.43] and circumferential strain in early diastole [0.37 ± 0.17 vs. 0.41 ± 0.15, p = 0.27] were similar between patients and controls, although peak circumferential systolic strain rate [-1.5 ± 0.3 vs. -1.6 ± 0.3 s(-1), p = 0.036] was reduced in c-SLE. Further analysis of patients revealed a negative correlation between LV PLSS and SLEDAI-2K (r = -0.52, p < 0.0001), and also between LV PLSS and the number of CRFs per patient (r = -0.32, p = 0.024). CONCLUSIONS: 2DST echocardiography has identified subclinical LV deformation impairment in c-SLE patients. Disease activity and cumulative exposure to CRFs contribute to myocardial compromise.

Subclinical right ventricle systolic dysfunction in childhood-onset systemic lupus erythematosus: insights from two-dimensional speckle-tracking echocardiography.

OBJECTIVE: The objective of this article is to evaluate right ventricle strain imaging by two-dimensional speckle-tracking (2DST) in childhood-onset systemic lupus erythematosus (c-SLE). METHODS: Thirty-five c-SLE patients with no signs or symptoms of heart failure and 33 healthy volunteers were evaluated by standard echocardiogram and 2DST. Conventional parameters included tricuspid annular plane systolic excursion (TAPSE), RV tissue-Doppler-derived Tei index and systolic pulmonary artery pressure. Global peak longitudinal systolic strain (PLSS) and strain rate (PLSSR) of RV were obtained by 2DST. Demographic/clinical features, SLEDAI-2K/SLICC/ACR-DI and treatment were also assessed. RESULTS: The median current age was similar in patients and controls (14.75 vs. 14.88 years, p = 0.62). RV PLSS was significantly reduced in c-SLE (-24.5 ± 5.09 vs. -27.62 ± 3.02%, p = 0.003). Similar findings were observed after excluding patients with pulmonary hypertension (-24.62 ± 4.87% vs. -27.62 ± 3.02%, p = 0.0041). RV PLSS was positively correlated with TAPSE (r = +0.49, p = 0.0027) and negatively correlated with Tei index (r = -0.34, p = 0.04) in c-SLE. RV PLSSR was not different comparing patients and controls (-0.65 s(-1 )± 0.47 vs. -1.87 ± 0.49 s(-1), p = 0.07). Further analysis of c-SLE patients revealed higher frequencies of neuropsychiatric manifestations (39% vs. 0%, p = 0.007) and antiphospholipid antibodies (55% vs. 18%, p = 0.035) in those with RV PLSS ≤ -23.7% vs >-23.7%. No differences were evidenced in demographic data, disease activity/damage or treatments (p > 0.05). CONCLUSIONS: The present study, using a new and more sensitive technique, revealed subclinical RV systolic dysfunction in c-SLE patients that may have future prognostic implications. The novel association of asymptomatic RV dysfunction with neuropsychiatric manifestations and antiphospholipid antibodies may suggest common physiopathological pathways.

Report of a Large Brazilian Family With a Very Attenuated Form of Hunter Syndrome (MPS II).

Hunter syndrome, or Mucopolysaccharidosis type II (MPS II), is a rare X-linked recessive disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). The phenotypic spectrum varies from severe to attenuated clinical forms. We report a large Brazilian family with 16 affected individuals exhibiting a very attenuated form of MPS II. Fourteen female carriers were also identified. Twelve affected male patients, whose ages ranged from 1 to 35 years, were examined. Molecular analysis showed a novel missense mutation (p.A77D) in the IDS gene, confirming the diagnosis. Nine of the family members presented some degree of heart damage, though only the proband became symptomatic and required heart transplantation. One 19-year-old adult and 1-year-old twin boys each had a normal echocardiogram. Short stature was found in two adults while macrocephaly was found in one; the remaining adults had anthropometric measures within normal range. All affected adults had normal cognitive development and were able to perform normal daily activities, except one who had mild learning disability. Two patients died due to natural causes beyond 70 years of age. The female carriers did not present any signs of disease. In this large family with a mild form of MPS II and variable degree of clinical manifestations, it is noteworthy that several affected individuals have remained asymptomatic even at advanced age and even without enzyme replacement therapy.