Upper airway obstructive disease in mucopolysaccharidoses: polysomnography, computed tomography and nasal endoscopy findings.

In mucopolysaccharidoses, upper airway obstruction has multiple causative factors and progressive respiratory disease may severely affect morbidity and mortality. In a cross-sectional study over 2 years we evaluated upper airway obstructive disease through overnight polysomnography, upper airway computed tomography and nasal endoscopy in 5 children and 6 adults with mucopolysaccharidoses of various types. Measurements of apnoea and apnoea-hypopnoea index, arousal index, and sleep efficiency were obtained through polysomnography. Retropalatal and retroglossal spaces were calculated through computed tomography, and the degree of adenoid hypertrophy was assessed through endoscopy. Apnoea index and apnoea-hypopnoea index were significantly higher in children than in adults with mucopolysaccharidoses (p = 0.03 and p = 0.03, respectively). Compared to healthy controls, retropalatal and retroglossal spaces were significantly smaller in children (p = 0.03 and p = 0.004, respectively) or adults with mucopolysaccharidoses (p = 0.004 and p = 0.004, respectively). All subjects had adenoid hypertrophy causing first-degree (36%) or second-degree (64%) obstruction at endoscopy. Overnight polysomnography, upper airway computed tomography and nasal endoscopy are useful tools for diagnosing obstructive sleep apnoea syndrome in mucopolysaccharidoses, and identifying the site and severity of airway obstruction.

[Fabry nephropathy in a female with superposed IgA glomerulonephritis]. / Nefropatia da malattia di Fabry in donna eterozigote con sovraimposta glomerulonefrite da IgA.

BACKGROUND: In Anderson-Fabry disease (AFd), the kidney is affected in all hemizygous males and in some heterozygous females. Female carriers can present subtle renal abnormalities due to glycosphingolipid (GSL) accumulation within renal cells. Renal biopsy is rarely performed in female Fabry patients because clinical renal manifestations are usually lacking. However, female carriers can accumulate GSL in their renal cells despite the absence of clinically evident kidney disease. CASE REPORT: We performed a kidney biopsy in a 52-year-old female patient, a Fabry disease carrier. The patient showed normal glomerular filtration rate, persistent microhematuria and proteinuria (about 1.7 g/24 hr), cornea "verticillata", and evident left ventricular hypertrophy. The molecular study documented a missense mutation R227Q in exon 5 of the alpha-galactosidase A gene. Optical microscopy showed electron-dense mesangial deposits due IgA glomerulonephritis, as confirmed by immunofluorescence. We decided to start therapy with angiotensin-converting enzyme inhibitors (ACE-I). After 8 months of treatment, the patient demonstrated proteinuria of 0.9 g/24 hr. To decide when to start treatment using enzyme replacement therapy (ERT) with human recombinant GAL A (Fabrazyme), we decided to perform an electron microscopy study of the renal biopsy. The renal ultrastructural findings were typical GSL inclusions in all kinds of glomerular cells, in tubular epithelial cells and in endothelial cells of interstitial capillaries, confirming the hypothesis of Fabry nephropathy. Consequently, Fabrazyme was given at a standard dose of 1 mg/kg every 2 weeks. After 24 months of combined treatment (ACE-I-Fabrazyme), proteinuria decreased to 0.2 g/24 hr. CONCLUSIONS: The importance of performing the ultrastructural examination of the kidney biopsy is stressed, especially in heterozygous Fabry patients to evaluate the need to treat them with ERT and to evaluate the degree of renal involvement.

Enzyme replacement therapy with agalsidase beta improves cardiac involvement in Fabry's disease.

Fabry's disease is an X-linked lysosomal storage disease caused by a deficiency of alpha-galactosidase that results in an accumulation of neutral glycosphingolipids throughout the body, including the cardiovascular system. Fabry cardiomyopathy, characterized by progressive severe concentric left ventricular (LV) hypertrophy, is very frequent and is the most important cause of death in affected patients. Enzyme replacement therapy (ERT) allows a specific treatment for this disease, however, there are very few data on the effectiveness of therapy on cardiac involvement. Nine patients with Fabry cardiac disease were studied on basal condition and after 6 and 12 months of treatment with algasidase beta (Fabrazyme). A complete clinical, electrocardiographic and echocardiographic evaluation was performed in all patients. Interpretable Doppler recordings of transmitral flow and pulmonary flow velocity curves were also acquired. At baseline, the patients with Fabry's disease had increased LV septum and posterior wall thickness, normal LV fractional shortening, LV ejection fraction, normal Doppler parameters of mitral inflow but a duration of pulmonary vein flow velocity wave exceeding that of the mitral wave at atrial systole. ERT did not affect heart rate and arterial pressure. LV internal diameters did not change, there was a slight but not significant decrease in the LV posterior wall thickening and a progressive decrease in the interventricular septum thickening (p < 0.025) and in LV mass (p < 0.001) The difference in duration between pulmonary vein flow velocity wave and mitral wave at atrial systole significantly decreased (p < 0.001). These results suggest that ERT in patients with Fabry cardiomyopathy is able to reduce the LV mass and ameliorate the LV stiffness.

[Anderson-Fabry's disease: diagnostic problems, therapeutic relevance, and clinical experience in the treatment of the disease with enzyme replacement therapy in nephropathic patients]. / Malattia di Anderson-Fabry: problematiche diagnostiche, attualità terapeutiche ed esperienza clinica nel trattamento della malattia con terapia enzimatica sostitutiva in pazienti nefropatici.

Aim of this study was to confirm the initial results of a clinical trial on the treatment of Fabry's disease carried out in 13 Italian Nephrology Units. Fabry's disease is a rare, X-linked inherited disease, characterized by a-galactosidase (a-GAL) deficiency, a lysosomial enzymatic activity that results in the accumulation of neutral glycosphingolipids in the endothelial cells of the whole body, and causes painful crises, acroparesthesiae, angiokeratomas, corneal and lens dystrophy, and progressive damage to kidneys, heart and central nervous system, as well as potentially leading to death. The present availability of the recombinant form of a-GAL allows us to prevent or stop the long-term complications of this disease. A clinical trial, generously supported by Genzyme, was started on February 2001. In this trial 20 patients affected by Fabry's disease were periodically treated with agalsidase-beta, the commercial form of the enzyme. The initial results of the trial have indicated that the drug is capable of reducing both the number and intensity of painful crises, improving the patient's sensation of well-being, thus suggesting that this therapeutic approach might theoretically increase life expectancy in these patients.

Case of Myhre syndrome with autism and peculiar skin histological findings.

Myhre syndrome (MS) (MIM 139210) is a rare disorder characterized by short stature, mental retardation, muscular build, blepharophimosis, and decreased joint mobility. We report on a 14-year-old boy with clinical findings consistent with a diagnosis of Myhre syndrome, associated with autism and peculiar skin histological findings.