scholarly journals Multiple Sulfatase Deficiency: A Disease Comprising Mucopolysaccharidosis, Sphingolipidosis, and More Caused by a Defect in Posttranslational Modification

2020 ◽  
Vol 21 (10) ◽  
pp. 3448 ◽  
Author(s):  
Lars Schlotawa ◽  
Laura A. Adang ◽  
Karthikeyan Radhakrishnan ◽  
Rebecca C. Ahrens-Nicklas
Keyword(s):  
Catalytic Activity ◽  
Disease Severity ◽  
Clinical Features ◽  
Age Of Onset ◽  
Systemic Disease ◽  
Clinical Aspects ◽  
Lysosomal Storage ◽  
Multiple Sulfatase Deficiency ◽  
Detection Of Mutations ◽  
Cellular Pathology

Multiple sulfatase deficiency (MSD, MIM #272200) is an ultra-rare disease comprising pathophysiology and clinical features of mucopolysaccharidosis, sphingolipidosis and other sulfatase deficiencies. MSD is caused by impaired posttranslational activation of sulfatases through the formylglycine generating enzyme (FGE) encoded by the sulfatase modifying factor 1 (SUMF1) gene, which is mutated in MSD. FGE is a highly conserved, non-redundant ER protein that activates all cellular sulfatases by oxidizing a conserved cysteine in the active site of sulfatases that is necessary for full catalytic activity. SUMF1 mutations result in unstable, degradation-prone FGE that demonstrates reduced or absent catalytic activity, leading to decreased activity of all sulfatases. As the majority of sulfatases are localized to the lysosome, loss of sulfatase activity induces lysosomal storage of glycosaminoglycans and sulfatides and subsequent cellular pathology. MSD patients combine clinical features of all single sulfatase deficiencies in a systemic disease. Disease severity classifications distinguish cases based on age of onset and disease progression. A genotype- phenotype correlation has been proposed, biomarkers like excreted storage material and residual sulfatase activities do not correlate well with disease severity. The diagnosis of MSD is based on reduced sulfatase activities and detection of mutations in SUMF1. No therapy exists for MSD yet. This review summarizes the unique FGE/ sulfatase physiology, pathophysiology and clinical aspects in patients and their care and outlines future perspectives in MSD.

scholarly journals Late infantile form of multiple sulfatase deficiency

2020 ◽  
Vol 2020 ◽  
Author(s):  
Nami Mohammadian Khonsari ◽  
Benyamin Hakak-Zargar ◽  
Tessa Voth ◽  
Shahab Noorian
Keyword(s):  
Age Of Onset ◽  
Signs And Symptoms ◽  
List Type ◽  
Lysosomal Storage ◽  
Skin Changes ◽  
Multiple Sulfatase Deficiency ◽  
Developmental Regression ◽  
Function Impairment ◽  
Health Complications ◽  
Learning Points

Summary Multiple sulfatase deficiency (MSD) is a lysosomal storage disorder (LSD) that results in the accumulation of sulfate esters which go on to cause neurological deterioration and mental delay, skin changes, and dysmorphism. The disease can be categorized into three subtypes based on the age of onset: neonatal, late infantile, or juvenile. Our patient is a 2.5-year-old girl, the only child of a healthy couple. Prior to the presentation of the disease, she had not been noted to have any previous health complications. The condition began at the age of 6 months with developmental regression and global hypotonia. Following thorough evaluation and testing, the patient was diagnosed with severe late infantile MSD, although some features, such as minimal mental deterioration, minimal dysmorphic facial features, and minimal organ enlargement, did not fully correlate with the diagnosis, since in cases of severe forms of the condition these features are almost always quite marked. The unexpected minimalism of some of the patient’s MSD signs in spite of the severity of her MSD condition made her case worth further studying. Learning points: Treating dermatologic signs and symptoms greatly eased our patient’s discomfort. We would suggest the use of appropriate supportive treatment for symptom management regardless of the life expectancy of the patient. As regards the diagnosis of MLD, given that in some cases the patient may present with irregular features of the condition, a genetic evaluation may be useful for accurate diagnosis. If motor function impairment is followed by dermatologic involvement, as seen in our patient and in many cases in the literature, MSD must be considered, and additional tests should be done to rule it out.

Multiple Sulfatase Deficiency: A Case Series With a Novel Mutation

2018 ◽  
Vol 33 (13) ◽  
pp. 820-824 ◽  
Author(s):  
Leen Hijazi ◽  
Amna Kashgari ◽  
Majid Alfadhel
Keyword(s):  
Intellectual Disability ◽  
White Matter ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Case Series ◽  
Periventricular White Matter ◽  
White Matter Disease ◽  
Lysosomal Storage ◽  
Multiple Sulfatase Deficiency ◽  
Developmental Regression

Multiple sulfatase deficiency is an autosomal recessive lysosomal storage disorder due to a deficiency in formylglycine-generating enzyme, which is encoded by the Sulfatase Modifying Factor 1 ( SUMF1) gene. Clinically, the disorder is variable. The most common characteristics are developmental regression, intellectual disability, ichthyosis, and periventricular white matter disease. Herein, we report 6 Saudi patients with multiple sulfatase deficiency caused by a novel homozygous missense mutation in the SUMF1 gene (NM_182760.3; c.785A>G [p.Gln262Arg]). The patients are 2 females and 4 males between 5 and 13 years of age, with an age of onset of 1 to 3 years. All patients are consanguineous and suffer from developmental regression, intellectual disability, ichthyosis, and periventricular white matter disease. This cohort differs from previous cohorts because of the absence of organomegaly and skeletal abnormalities.

scholarly journals Clinical features and treatment with botulinum toxin in blepharospasm: a 17-year experience

2012 ◽  
Vol 70 (9) ◽  
pp. 662-666 ◽  
Author(s):  
Camila Catherine Aquino ◽  
Andre C. Felício ◽  
Pollyanna Celso Felipe de Castro ◽  
Ricardo Araujo Oliveira ◽  
Sonia Maria Cesar Azevedo Silva ◽  
...  
Keyword(s):  
Botulinum Toxin ◽  
Clinical Features ◽  
Age Of Onset ◽  
Smoking History ◽  
Clinical Aspects ◽  
Lower Face ◽  
Therapeutic Outcomes ◽  
History Of ◽  
Botulinum Toxin Treatment ◽  
The Mean

OBJECTIVE: It was to analyze clinical aspects of patients with blepharospasm, including outcomes of botulinum toxin treatment. Additionally, clinical characteristics of isolated blepharospasm were compared to those of blepharospasm plus other movement disorders. METHODS: Clinical data recorded during 17 years were reviewed. The variables included age, gender, age of onset, past medical history, head trauma, smoking history, family history of dystonia, severity, duration of botulinum toxin relief and adverse effects. RESULTS: A total of 125 patients were included and 75.2% were female. The mean age of onset was 54.3 years; 89.6% of the individuals started with contractions in eye region, and 39.2% of them spread to lower face or neck. Isolated blepharospasm group was compared with blepharospasm-plus group for demographic and clinical features, and therapeutic outcomes, without significant differences. Botulinum toxin treatment improved the severity of contractions (p=0.01) with low rate of side effects (14%). CONCLUSIONS: Both groups - isolated blepharospasm and blepharospasm-plus - shared similar results concerning epidemiology, clinical features and therapeutic response to botulinum toxin.

Saudi Variant of Multiple Sulfatase Deficiency

1992 ◽  
Vol 7 (1_suppl) ◽  
pp. S12-S21 ◽  
Author(s):  
A. Al Aqeel ◽  
P.T. Ozand ◽  
J. Brismar ◽  
G.G. Gascon ◽  
G. Brismar ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Lysosomal Storage Diseases ◽  
Cord Compression ◽  
Cervical Cord ◽  
Lysosomal Storage ◽  
Childhood Onset ◽  
Inborn Errors ◽  
Juvenile Form ◽  
Multiple Sulfatase Deficiency ◽  
Sulfatase Activity

We describe eight patients with multiple sulfatase deficiency (MSD, or Austin's disease) who differ phenotypically from classic neonatal-, childhood-, or juvenile-onset MSD. The age of onset was in childhood. The patients presented with somatic and facial features of mucopolysaccharidosis reminiscent of Maroteaux-Lamy and Morquio syndromes. They differed from classic MSD by the presence of corneal cloudiness, macrocephaly, severe dysostosis multiplex, and gibbus and the absence of ichthyosis, retinal degeneration, severe deafness, severe mental retardation, and dementia. The main neurologic presentation was cervical cord compression due to axis abnormalities. Despite neuroradiologic evidence of white-matter changes, neurologic presentation was not like metachromatic leukodystrophy. The sulfatase deficiencies were more marked than in the classic juvenile form of MSD, but less marked than in the classic childhood-onset form of MSD. Steroid sulfatase activity was spared except in one patient. This Saudi variant of MSD accounts for 5% of all lysosomal storage diseases in the Cell Repository Registry of our Inborn Errors of Metabolism Laboratory. (J Child Neurol 1992;7(Suppl):S12-S21.)

scholarly journals AB0442 CLINICAL FEATURES OF POLYMYOSITIS AND DERMATOMYOSITIS PATIENTS WITH SEVERE DYSPHAGIA

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1249.1-1249
Author(s):  
Y. Hayashi ◽  
K. Izumi ◽  
S. Hama ◽  
M. Higashida-Konishi ◽  
M. Ushikubo ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
Clinical Features ◽  
Clinical Characteristics ◽  
Age Of Onset ◽  
Inflammatory Diseases ◽  
Medical Center ◽  
Hospital Organization ◽  
Initial Examination ◽  
Severe Dysphagia ◽  
Frequent Complication

Background:Polymyositis (PM) and dermatomyositis (DM) are autoimmune inflammatory diseases characterized by proximal myositis. Dysphagia has been reported to develop in 35 to 62% of PM/DM patients and known as poor prognosis factor.Objectives:The purpose of this study is to determine the clinical characteristics of PM/DM patients who present with deglutition disorder.Methods:Consecutive patients with PM/DM who visited National Hospital Organization Tokyo Medical Center between April 2010 and January 2021 are included in this study. We compared clinical features between the patients with and without dysphagia. The diagnosis of dysphagia was based on videofluorography swallow study, and dysphagia requiring gastrostomy was defined as severe dysphagia. The clinical characteristics compared in this study were following: age of onset, levels of serum creatine kinase (CK) and lactate dehydrogenase(LDH), sense of dysphagia, manual muscle test (MMT) score, and complication of malignancy or interstitial pneumonia.Results:A total of 73 patients with PM/DM were identified. Among them, 12 patients were diagnosed with dysphagia, and 5 patients developed severe dysphagia. Patients with dysphagia had the following characteristics compared to patients without dysphagia: higher levels of serum LDH (833.7 ± 500.1 U/L vs 471.9 ± 321.0 U/L, p = 0.0088), higher levels of serum CK at initial examination (6070.3 ± 7184.8 IU/L vs 1534.7 ± 2978.8 IU/L, p = 0.0086) and more frequent sense of dysphagia (90.9% vs 10.6%, p< 0.0001), lower MMT score(3.18 ± 1.07 vs 4.31 ± 0.75, p = 0.0017). In addition to those, patients with severe dysphagia presented older age of onset (mean age 69.4 ± 12.0 vs 51.7 ± 14.8, p = 0.014), more frequent complication of malignancy (80.0% vs 14.8%, p= 0.0048) and less frequent complication of interstitial pneumonia (0.0% vs 55.5%, p= 0.023).Conclusion:These results indicate that dysphagia develops frequently in PM/DM patients with higher levels of serum LDH or CK, sense of dysphagia and low MMT score. Among them, patients with elderly onset or malignancy are at risk for sever dysphagia, and should be treated carefully.Disclosure of Interests:None declared.

Clinical Features of Epistaxis in Dogs: A Retrospective Study of 35 Cases (1999–2002)

2005 ◽  
Vol 41 (3) ◽  
pp. 179-184 ◽  
Author(s):  
Jennifer L. Strasser ◽  
Eleanor C. Hawkins
Keyword(s):  
Retrospective Study ◽  
Cell Volume ◽  
Clinical Features ◽  
Packed Cell Volume ◽  
Systemic Disease ◽  
Facial Deformity

Epistaxis was retrospectively evaluated in 35 dogs. Systemic disease was diagnosed in seven dogs and intranasal disease in 29. Nineteen dogs with intranasal disease had neoplasia. Dogs with neoplasia were older (mean 10.0 years) than dogs with nonneoplastic intranasal disease (mean 5.6 years). Signs persisting for &gt;1 month occurred more often in dogs with intranasal than systemic disease. Unilateral epistaxis did not distinguish intranasal from systemic disease. Only dogs with intranasal disease had facial deformity, decreased airflow, or regional sub-mandibular lymphadenopathy. Dogs with systemic disease had a lower packed cell volume (mean 31.8%) than dogs with intranasal disease (mean 42.7%).

scholarly journals Focus on localized laryngeal amyloidosis: management of five cases

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 327-332
Author(s):  
Massimo Mesolella ◽  
Gerardo Petruzzi ◽  
Sarah Buono ◽  
Grazia Salerno ◽  
Francesco Antonio Salzano ◽  
...  
Keyword(s):  
Systemic Disease ◽  
Clinical Aspects ◽  
Benign Tumors ◽  
Local Form ◽  
Systemic Involvement ◽  
Clinical Syndromes ◽  
Laryngeal Amyloidosis ◽  
And Control ◽  
Localized Laryngeal Amyloidosis

AbstractAmyloidosis is a group of idiopathic clinical syndromes caused by the deposition of insoluble fibrillar proteins (amyloid) in the extracellular matrix of organs and tissues. These deposits disrupt the function of the target organ. Amyloidosis can manifest as a systemic disease or a single-organ involvement (local form). Its etiology still remains unclear. Deposits of amyloid in the larynx are rare, accounting for between 0.2 and 1.2% of benign tumors of the larynx. In this retrospective study, we report the clinical aspects, diagnosis, treatment and follow-up of five female patients with localized laryngeal amyloidosis without systemic involvement. The patients were all treated successfully using microlaryngoscopy with CO2 laser or cold instruments. Prognosis is excellent; however, appropriate follow-up is an important part of the long-term management of this disease in order to prevent and control the possibility of local recurrence.

Mucolipidosis Type IV: Clinical Spectrum and Natural History

PEDIATRICS ◽  
1987 ◽  
Vol 79 (6) ◽  
pp. 953-959
Author(s):  
Naomi Amir ◽  
Joel Zlotogora ◽  
Gideon Bach
Keyword(s):  
Age Of Onset ◽  
Clinical Manifestations ◽  
Psychomotor Retardation ◽  
Clinical Spectrum ◽  
Lysosomal Storage ◽  
Mucolipidosis Type Iv ◽  
Type Iv ◽  
First Year Of Life ◽  
Developmental Features ◽  
Mucolipidosis Type

The clinical spectrum and developmental features of mucolipidosis type IV, a recessive lysosomal storage disorder, are presented. The evaluation was based on information from the clinical charts and information obtained from the families of 20 patients between the ages of 2 to 17 years. The clinical manifestations of the disease, profound psychomotor retardation and visual impairment, appear during the first year of life. Definitive diagnosis is made by electron microscopy which reveals storage organelles typical of the mucolipidoses. This study details, for the first time, the heterogeneity of the ophthalmologic features, specifically as pertains to the age of onset, degree and clinical course of the corneal opacities, and the retinal involvement. Although the top developmental level was found to be 12 to 15 months in language and motor function, the course of the disease is protracted for some children, who show only a slight improvement, and others, little if any deterioration despite the early infantile onset of the disease. This presentation provides guidelines for the clinical diagnosis of mucolipidosis type IV.

scholarly journals Small–molecule therapeutics for the treatment of glycolipid lysosomal storage disorders

2003 ◽  
Vol 358 (1433) ◽  
pp. 927-945 ◽  
Author(s):  
Terry D. Butters ◽  
Howard R. Mellor ◽  
Keishi Narita ◽  
Raymond A. Dwek ◽  
Frances M. Platt
Keyword(s):  
Catalytic Activity ◽  
Lysosomal Storage Disorders ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
Substrate Reduction ◽  
Treatment Demand ◽  
Small Molecule Therapeutics ◽  
Storage Disorders

Glycosphingolipid (GSL) lysosomal storage disorders are a small but challenging group of human diseases to treat. Although these disorders appear to be monogenic in origin, where the catalytic activity of enzymes in GSL catabolism is impaired, the clinical presentation and severity of disease are heterogeneous. Present attitudes to treatment demand individual therapeutics designed to match the specific disease–related gene defect; this is an acceptable approach for those diseases with high frequency, but it lacks viability for extremely rare conditions. An alternative therapeutic approach termed ‘substrate deprivation’ or ‘substrate reduction therapy’ (SRT) aims to balance cellular GSL biosynthesis with the impairment in catalytic activity seen in lysosomal storage disorders. The development of N–alkylated iminosugars that have inhibitory activity against the first enzyme in the pathway for glucosylating sphingolipid in eukaryotic cells, ceramide–specific glucosyltransferase, offers a generic therapeutic for the treatment of all glucosphingolipidoses. The successful use of N–alkylated iminosugars to establish SRT as an alternative therapeutic strategy has been demonstrated in in vitro , in vivo and in clinical trials for type 1 Gaucher disease. The implications of these studies and the prospects of improvement to the design of iminosugar compounds for treating Gaucher and other GSL lysosomal storage disorders will be discussed.

scholarly journals Clinical Features and Echocardiographic Findings in Children with Hypertrophic Cardiomyopathy

2013 ◽  
Vol 59 (6) ◽  
pp. 285-288
Author(s):  
Blesneac Cristina ◽  
Benedek Theodora ◽  
Togănel Rodica ◽  
Benedek I
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Age Of Onset ◽  
Adult Population ◽  
Systemic Disease ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Septal Myectomy ◽  
Sarcomeric Protein ◽  
Asymptomatic Patients ◽  
Left Ventricular Outflow

Abstract Background: Hypertrophic cardiomyopathy, one of the most common inherited cardiomyopathies, is a heterogeneous disease resulting from sarcomeric protein mutations, with an incidence in the adult population of 1:500. Current information on the epidemiology and outcomes of this disease in children is limited. Methods: Thirty-four children diagnosed with hypertrophic cardiomyopathy in the Pediatric Cardiology Department from Tîrgu Mureș were evaluated concerning familial and personal history, clinical, paraclinical and therapeutic aspects. Hypertrophic cardiomyopathy was defined by the presence of a hypertrophied, non-dilated ventricle, in the absence of a cardiac or systemic disease that could produce ventricular hypertrophy. Results: The youngest diagnosed child was a neonate, a total of 10 patients being diagnosed until 1 year of age. In 6 cases a positive familial history was found. Noonan syndrome was found in 2 cases. Only 21 patients were symptomatic, the predominant symptoms being shortness of breath on exertion with exercise limitations. Left ventricular outflow tract obstruction was present in 21 cases (61.7%). Twenty-four patients were on β-blocking therapy, while 4 patients underwent septal myectomy. Conclusions: Hypertrophic cardiomyopathy is a heterogeneous disorder in terms of evolution, age of onset, type and extent of hypertrophy, and the risk of sudden death. It can affect children of any age. There is a need for a complex evaluation, including familial and personal anamnesis, clinical examination, electrocardiogram and echocardiography of all patients. It is highly important to develop screening strategies, including genetic testing, for an early diagnosis, especially in asymptomatic patients with a positive familial background

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