scholarly journals Acute Gaucher Disease-Like Condition in an Indian Infant with a Novel Biallelic Mutation in the Prosaposin Gene

2018 ◽  
Vol 08 (02) ◽  
pp. 081-085 ◽  
Author(s):  
Akella Radha Rama Devi ◽  
Srilatha Kadali ◽  
Ananthaneni Radhika ◽  
Vineeta Singh ◽  
M. Kumar ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Stop Codon ◽  
Normal Activity ◽  
Acid Sphingomyelinase ◽  
Biallelic Mutation ◽  
Saposin C ◽  
Cherry Red Spot ◽  
Clonic Seizures ◽  
Refractory Seizures ◽  
Indian Infant

AbstractThis is the first reported case of prosaposin (PSAP) mutation from India manifesting as an acute neuronal Gaucher disease-like condition. A 2-month-old male baby presented with encephalopathy, resistant tonic–clonic seizures, moderate hepatosplenomegaly, hypotonia, and cherry red spot in the retinae. The child had anemia, thrombocytopenia, elevated chitotriosidase, and normal activity of acid sphingomyelinase and low normal activity of β-glucosidase 1 (β-glucocerebrosidase 1, GBA). The child succumbed in the fourth month of life due to persistent respiratory distress and refractory seizures. The clinical phenotype, cherry red spots, elevated chitotriosidase, and lysosomal assays led to the suspicion of Gaucher disease. Exome sequencing revealed a homozygous stop codon mutation in the PSAP gene (c.G1228T, p.Glu410ter). Prenatal diagnosis in the next pregnancy revealed a carrier fetus, who was unaffected postnatally. The diagnosis of specific activator deficiency such as saposin C and saposin D deficiency (in the current study) should be considered and tested for when Gaucher disease is suspected in an infant with partially deficient or near normal GBA activity.

Non-neuronopathic Gaucher disease due to saposin C deficiency

2007 ◽  
Vol 72 (6) ◽  
pp. 538-542 ◽  
Author(s):  
A Tylki-Szymańska ◽  
B Czartoryska ◽  
M-T Vanier ◽  
BJMH Poorthuis ◽  
JAE Groener ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Saposin C

Prevalence of Gaucher Disease (GD) in Patients with Unknown Cause of Splenomegaly and/or Thrombocytopenia in Saudi Arabia: A Multicenter Cross-sectional Study Protocol (Preprint)

2021 ◽  
Author(s):  
Abdulelah Qadi ◽  
Aly Ezzat ◽  
Ayman Al Hejazi ◽  
Fahad Al Abbas ◽  
Ghaleb Elyamany ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Gaucher Disease ◽  
Cross Sectional Study ◽  
Primary Objective ◽  
High Risk Group ◽  
Acid Sphingomyelinase ◽  
Lysosomal Storage ◽  
Sectional Study ◽  
Eligibility Criteria ◽  
Cross Sectional

UNSTRUCTURED Background: Gaucher disease (GD) is the commonest form of Lysosomal storage disorders that are characterized by the accumulation of glucosylceramide within the lysosomes of cells that are ordinarily degraded to glucose and lipid components. The primary objective of this study is to determine the prevalence of Gaucher Disease in a high-risk group (defined as patients with splenomegaly and/or thrombocytopenia of unknown cause). Methods: The present multicenter, cross-sectional, study will include patients presenting with signs of splenomegaly and/or thrombocytopenia over a period of 12 months with no definitive cause. Eligible patients will be assessed for acid β-glucosidase and acid sphingomyelinase enzymes activity using dried blood spot (DBS) samples. A total of 400 patients from Saudi Arabia who fulfill the eligibility criteria will be enrolled in the study. Discussion: Saudi Arabia is the largest country in the Arabian Peninsula, with a population of more than 28 million. Despite healthcare being free to Saudi citizens, a number of potential barriers to healthcare access and individual healthcare-seeking have been reported. While Gaucher disease is a rare disease, its incidence in Saudi Arabia appears to be higher than other parts of the world. Nevertheless, no previous nationwide study was conducted to provide reliable data regarding the incidence and characteristics of Saudi patients with Gaucher Disease. There is a scarcity in the published literature regarding the treatment patterns and outcomes of Gaucher Disease in Saudi Arabia as well.

scholarly journals A Guided Tour of the Structural Biology of Gaucher Disease: Acid-β-Glucosidase and Saposin C

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Raquel L. Lieberman
Keyword(s):  
Crystal Structures ◽  
Structural Biology ◽  
Gaucher Disease ◽  
Lysosomal Storage ◽  
The Past ◽  
Current State ◽  
Saposin C ◽  
Prevalent Disease ◽  
Guided Tour ◽  
Insight Into

Mutations in both acid-β-glucosidase (GCase) and saposin C lead to Gaucher disease, the most common lysosomal storage disorder. The past several years have seen an explosion of structural and biochemical information for these proteins, which have provided new insight into the biology and pathogenesis of Gaucher disease, as well as opportunities for new therapeutic directions. Nearly 20 crystal structures of GCase are now available, from different heterologous sources, complexed with different ligands in the active site, in different glycosylation states, as well as one that harbors a prevalent disease-causing mutation, N370S. For saposin C, two NMR and 3 crystal structures have been solved, each with its unique snapshot. This review focuses on the details of these structures to highlight salient common and disparate features that contribute to our current state of knowledge of this complex orphan disease.

scholarly journals Gaucher disease due to saposin C deficiency is an inherited lysosomal disease caused by rapidly degraded mutant proteins

2014 ◽  
Vol 23 (21) ◽  
pp. 5814-5826 ◽  
Author(s):  
Marialetizia Motta ◽  
Serena Camerini ◽  
Massimo Tatti ◽  
Marialuisa Casella ◽  
Paola Torreri ◽  
...  
Keyword(s):  
Gaucher Disease ◽  
Lysosomal Disease ◽  
Mutant Proteins ◽  
Saposin C

scholarly journals A child with global neuroregression with refractory epilepsy

2014 ◽  
Vol 01 (02) ◽  
pp. 092-093
Author(s):  
Rachana Dubey ◽  
Biswaroop Chakrabarty ◽  
Sheffali Gulati ◽  
Atin Kumar
Keyword(s):  
White Matter ◽  
Refractory Epilepsy ◽  
Wide Spectrum ◽  
Global Developmental Delay ◽  
Mri Brain ◽  
Insidious Onset ◽  
Hexosaminidase A ◽  
Cherry Red Spot ◽  
Radiological Changes ◽  
Refractory Seizures

AbstractHypomyelinating disorders have wide spectrum of clinical and radiological manifestations. A 17-month-old girl presented with baseline global developmental delay with insidious onset global neuroregression with refractory seizures from 1 year of age. Her birth and family history were noncontributory. Salient features on examination were central hypotonia and retinal cherry red spot. MRI Brain revealed characteristic white matter and basal ganglia changes. Her serum hexosaminidase A levels were undetectable. Identification of these radiological changes is crucial in directing appropriate enzyme and mutation testing in these patients.

scholarly journals Saposin C mutations in Gaucher disease patients resulting in lysosomal lipid accumulation, saposin C deficiency, but normal prosaposin processing and sorting

2010 ◽  
Vol 19 (15) ◽  
pp. 2987-2997 ◽  
Author(s):  
A. M. Vaccaro ◽  
M. Motta ◽  
M. Tatti ◽  
S. Scarpa ◽  
L. Masuelli ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Gaucher Disease ◽  
Saposin C

scholarly journals Autophagy in Gaucher disease due to saposin C deficiency

Autophagy ◽  
2011 ◽  
Vol 7 (1) ◽  
pp. 94-95 ◽  
Author(s):  
Massimo Tatti ◽  
Marialetizia Motta ◽  
Rosa Salvioli
Keyword(s):  
Gaucher Disease ◽  
Saposin C

scholarly journals Dexamethasone as Abortive Treatment for Refractory Seizures or Status Epilepticus in the Inpatient Setting

2019 ◽  
Vol 7 ◽  
pp. 232470961984881 ◽  
Author(s):  
Alexander B. Ramos ◽  
Roberto A. Cruz ◽  
Nicole R. Villemarette-Pittman ◽  
Piotr W. Olejniczak ◽  
Edward C. Mader
Keyword(s):  
Status Epilepticus ◽  
Cost Of Care ◽  
Nonconvulsive Status Epilepticus ◽  
Inpatient Setting ◽  
Left Frontal Lobe ◽  
Epilepsia Partialis Continua ◽  
Line Therapy ◽  
History Of ◽  
Clonic Seizures ◽  
Refractory Seizures

Refractory seizures or status epilepticus (RS/SE) continues to be a challenge in the inpatient setting. Failure to abort a seizure with antiepileptic drugs (AEDs) may lead to intubation and treatment with general anesthesia exposing patients to complications, extending hospitalization, and increasing the cost of care. Studies have shown a key role of inflammatory mediators in seizure generation and termination. We describe 4 patients with RS/SE that was aborted when dexamethasone was added to conventional AEDs: a 61-year-old female with temporal lobe epilepsy who presented with delirium, nonconvulsive status epilepticus, and oculomyoclonic status; a 56-year-old female with history of traumatic left frontal lobe hemorrhage who developed right face and hand epilepsia partialis continua followed by refractory focal clonic seizures; a 51-year-old male with history of traumatic intracranial hemorrhage who exhibited left-sided epilepsia partialis continua; and a 75-year-old female with history of breast cancer who manifested nonconvulsive status epilepticus and refractory focal clonic seizures. All patients continued experiencing RS/SE despite first- and second-line therapy, and one patient continued to experience RS/SE despite third-line therapy. Failure to abort RS/SE with conventional therapy motivated us to administer intravenous dexamethasone. A 10-mg load was given (except in one patient) followed by 4.0- 5.2 mg q6h. All clinical and electrographic seizures stopped 3-4 days after starting dexamethasone. When dexamethasone was discontinued 1-3 days after seizures stopped, all patients remained seizure-free on 2-3 AEDs. The cessation of RS/SE when dexamethasone was added to conventional antiseizure therapy suggests that inflammatory processes are involved in the pathogenesis of RS/SE.

scholarly journals A Novel Mutation in theCYP11B1Gene Causes Steroid 11β-Hydroxylase Deficient Congenital Adrenal Hyperplasia with Reversible Cardiomyopathy

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Mohammad A. Alqahtani ◽  
Ayed A. Shati ◽  
Minjing Zou ◽  
Ali M. Alsuheel ◽  
Abdullah A. Alhayani ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Stop Codon ◽  
Novel Mutation ◽  
Skin Pigmentation ◽  
Premature Stop Codon ◽  
Molecular Defect ◽  
Sequencing Analysis ◽  
Adrenal Hyperplasia ◽  
Biallelic Mutation ◽  
Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) due to steroid 11β-hydroxylase deficiency is the second most common form of CAH, resulting from a mutation in theCYP11B1gene. Steroid 11β-hydroxylase deficiency results in excessive mineralcorticoids and androgen production leading to hypertension, precocious puberty with acne, enlarged penis, and hyperpigmentation of scrotum of genetically male infants. In the present study, we reported 3 male cases from a Saudi family who presented with penile enlargement, progressive darkness of skin, hypertension, and cardiomyopathy. The elder patient died due to heart failure and his younger brothers were treated with hydrocortisone and antihypertensive medications. Six months following treatment, cardiomyopathy disappeared with normal blood pressure and improvement in the skin pigmentation. The underlying molecular defect was investigated by PCR-sequencing analysis of all coding exons and intron-exon boundary of theCYP11B1gene. A novel biallelic mutation c.780 G>A in exon 4 of theCYP11B1gene was found in the patients. The mutation created a premature stop codon at amino acid 260 (p.W260∗), resulting in a truncated protein devoid of 11β-hydroxylase activity. Interestingly, a somatic mutation at the same codon (c.779 G>A,p.W260∗) was reported in a patient with papillary thyroid cancer (COSMIC database). In conclusion, we have identified a novel nonsense mutation in theCYP11B1gene that causes classic steroid 11β-hydroxylase deficient CAH. Cardiomyopathy and cardiac failure can be reversed by early diagnosis and treatment.

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