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 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.

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 Age‐related ventricular expansion is not spatially concordant with MR‐visible periventricular white matter disease

2021 ◽  
Vol 17 (S1) ◽  
Author(s):  
Daniel L Schwartz ◽  
Caela Hung ◽  
David Lahna ◽  
Natalie E Roese ◽  
Randy L Woltjer ◽  
...  
Keyword(s):  
White Matter ◽  
Periventricular White Matter ◽  
White Matter Disease ◽  
Age Related ◽  
Mr Visible

scholarly journals Postural Complexity Influences Development in Infants Born Preterm With Brain Injury: Relating Perception-Action Theory to 3 Cases

2014 ◽  
Vol 94 (10) ◽  
pp. 1508-1516 ◽  
Author(s):  
Stacey C. Dusing ◽  
Theresa Izzo ◽  
Leroy R. Thacker ◽  
James Cole Galloway
Keyword(s):  
White Matter ◽  
Postural Control ◽  
Developmental Delays ◽  
Action Theory ◽  
Center Of Pressure ◽  
Case Series ◽  
White Matter Injury ◽  
Periventricular White Matter ◽  
Postural Control System ◽  
Perception Action

Background and Purpose Perception-action theory suggests a cyclical relationship between movement and perceptual information. In this case series, changes in postural complexity were used to quantify an infant's action and perception during the development of early motor behaviors. Case Description Three infants born preterm with periventricular white matter injury were included. Outcomes Longitudinal changes in postural complexity (approximate entropy of the center of pressure), head control, reaching, and global development, measured with the Test of Infant Motor Performance and the Bayley Scales of Infant and Toddler Development, were assessed every 0.5 to 3 months during the first year of life. All 3 infants demonstrated altered postural complexity and developmental delays. However, the timing of the altered postural complexity and the type of delays varied among the infants. For infant 1, reduced postural complexity or limited action while learning to control her head in the midline position may have contributed to her motor delay. However, her ability to adapt her postural complexity eventually may have supported her ability to learn from her environment, as reflected in her relative cognitive strength. For infant 2, limited early postural complexity may have negatively affected his learning through action, resulting in cognitive delay. For infant 3, an increase in postural complexity above typical levels was associated with declining neurological status. Discussion Postural complexity is proposed as a measure of perception and action in the postural control system during the development of early behaviors. An optimal, intermediate level of postural complexity supports the use of a variety of postural control strategies and enhances the perception-action cycle. Either excessive or reduced postural complexity may contribute to developmental delays in infants born preterm with white matter injury.

scholarly journals Elevated Cerebellar Glucose Metabolism in Microvascular White Matter Disease: Normal Aging and Alzheimer's Disease

1988 ◽  
Vol 8 (3) ◽  
pp. 433-435 ◽  
Author(s):  
A. Klinger ◽  
M. J. de Leon ◽  
A. E. George ◽  
J. D. Miller ◽  
A. P. Wolf
Keyword(s):  
Computed Tomography ◽  
Positron Emission Tomography ◽  
White Matter ◽  
White Matter Lesions ◽  
Emission Tomography ◽  
Periventricular White Matter ◽  
White Matter Disease ◽  
Metabolic Rates ◽  
Positron Emission ◽  
Periventricular White Matter Lesions

Young normal, elderly, and clinically diagnosed Alzheimer disease subjects who had undergone positron emission tomography (PET) and computed tomography (CT) examinations were studied to determine the effect of periventricular white matter lesions on cerebellar glucose metabolic rates. PET-determined cerebellar metabolic rates were elevated in subjects with periventricular white matter lesions. These results suggest the cautious use of cortical-to-cerebellar ratios in future PET or single-photonemission CT (SPECT) studies.

Novel homozygousDEAF1variant suspected in causing white matter disease, intellectual disability, and microcephaly

2014 ◽  
Vol 164 (6) ◽  
pp. 1565-1570 ◽  
Author(s):  
Eissa A. Faqeih ◽  
Mohammed Al-Owain ◽  
Dilek Colak ◽  
Rosan Kenana ◽  
Yusra Al-Yafee ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
White Matter ◽  
White Matter Disease

scholarly journals Galactosialidosis in a newborn with a novel mutation in the CTSA gene presenting with transient hyperparathyroidism

2017 ◽  
Vol 20 (2) ◽  
pp. 95-97
Author(s):  
E Okulu ◽  
G Tunc ◽  
T Eminoglu ◽  
O Erdeve ◽  
B Atasay ◽  
...  
Keyword(s):  
Lysosomal Storage Disease ◽  
Autosomal Recessive ◽  
Storage Disease ◽  
Age Of Onset ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Inherited Disease ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Infantile Form

Abstract Galactosialidosis is a lysosomal storage disease caused by deficiency of protective protein that is encoded by the cathepsin A (CTSA) gene localized on chromosome 20q13.1. Mutations of this gene are the cause of galactosialidosis that result in loss of function of protective protein. Galactosialidosis is an autosomal recessive inherited disease and has been divided into three subtypes based on age of onset and the severity of clinical manifestations. We report an early infantile form of galactosialidosis in a newborn with a novel mutation on the CTSA gene.

scholarly journals Compound heterozygous mutations of two eIF2B genes in early childhood onset form of vanishing white matter disease

2020 ◽  
Author(s):  
Chunmei Wang ◽  
Fang Yuan ◽  
Shengnan Wu ◽  
Zhao Liu ◽  
Simei Wang ◽  
...  
Keyword(s):  
Protein Structure ◽  
White Matter ◽  
Missense Mutation ◽  
Novel Mutation ◽  
Compound Heterozygous ◽  
White Matter Disease ◽  
The Novel ◽  
Compound Heterozygous Mutations ◽  
Vanishing White Matter Disease ◽  
Vanishing White Matter

Abstract Background Diagnoses of vanishing white matter disease (VWMD) were difficult due to variable clinical features, severity, age of onset and wide range of mutations in eIF2G genes which cause VWMD. This study reported two novel mutations in eIF2B genes associated with VWMD to and expand our understanding of VWMD. Case presentation Relevant data from clinical diagnoses and genetic mutational analyses in two Chinese female patients with sporad­ic VWMD were collected and analyzed. Protein structure/function was predicted. The identity of biological parents was confirmed based on variants called from the next-generation sequencing (NGS) data. Compound heterozygous mutations, c.254 T>A (p.Val85Glu), and c.597+2delT in the EIF2B2 gene, c.545C>T(p.Thr182Met) and c.1340C>T(p.Ser447Leu) in the EIF2B5 gene were detected in the two patients. Further phenotype investigation of both patients enables the diagnosis of the vanishing white matter disease .Three missense mutation c.254 T>A (p.Val85Glu) in the EIF2B2 gene, c.545C>T(p.Thr182Met) and c.1340C>T(p.Ser447Leu) in the EIF2B5 gene have been found and predicted to be deleterious. All the three mutation causes hydrophobicity and stability changes of proteins, and all the mutations were localized in conserved sequences. One novel mutation of c.1340C>T(p.Ser447Leu) in the EIF2B5 gene ,and two other known mutations. The iterative threading assembly refinement (I-TASSER) server generated three-dimensional (3D) atomic models based on protein sequences from the novel missense mutation of c.1340C>T(p.Ser447Leu) in the EIF2B5 gene, which showed that the protein structure changed . The novel mutation c.597+2delT in the EIF2B2 gene may cause the splice site to disappear. We also analyzed mutations in missense mutations that cause VWMD and found that most of the t Pathogenic sites are localized in conserved NT and I-patch homology regions and the catalytic domain of EIF2Bε. Conclusions This study expands the spectrum of genotypes and phenotypes of VWMD and provides new insights into the molecular mechanism of VWMD and aide the acute diagnosis and treatment of VWMD.

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