scholarly journals The Natural History of Infantile Neuroaxonal Dystrophy

2020 ◽  
Author(s):  
Fadie D Altuame ◽  
Gretchen Foskett ◽  
Paldeep Atwal ◽  
Sarah Endemann ◽  
Mark Midei ◽  
...  
Keyword(s):  
Natural History ◽  
Neurodegenerative Disorder ◽  
Gastrointestinal Disease ◽  
Cerebellar Atrophy ◽  
Neuroaxonal Dystrophy ◽  
Fine Motor ◽  
Speech Impairment ◽  
Infantile Neuroaxonal Dystrophy ◽  
Significant Difference ◽  
History Of

Abstract Background: Infantile neuroaxonal dystrophy (INAD) is a rapidly progressive neurodegenerative disorder of early onset causing premature death. It results from biallelic pathogenic variants in PLA2G6, which encodes a calcium‐independent phospholipase A2. Objective: We aim to outline the natural history of INAD and provide a comprehensive description of its clinical, radiological, laboratory, and molecular findings. Materials and Methods: We comprehensively analyzed the charts of 28 patients: 16 patients from Riyadh, Saudi Arabia, 8 patients from North and South America and 4 patients from Europe with a molecularly confirmed diagnosis of PLA2G6‐associated neurodegeneration (PLAN) and a clinical history consistent with INAD.Results: In our cohort, speech impairment and loss of gross motor milestones were the earliest signs of the disease. As the disease progressed, loss of fine motor milestones and bulbar dysfunction were observed. Temporo-frontal function was among the last of the milestones to be lost. Appendicular spastic hypertonia, axial hypotonia, and hyperreflexia were common neurological findings. Other common clinical findings include nystagmus (60.7%), seizures (42.9%), gastrointestinal disease (42.9%), skeletal deformities (35.7%), and strabismus (28.6%). Cerebellar atrophy and elevations in serum AST and LDH levels were consistent features of INAD. There was a statistically significant difference when comparing patients with non-sense/truncating variants compared with missense/in-frame deletions in the time of initial concern (p = 0.04), initial loss of language (p = 0.001), initial loss of fine motor skills (p = 0.009), and initial loss of bulbar skills (p = 0.007).Conclusion: INAD is an ultra-rare neurodegenerative disorder that presents in early childhood, with a relentlessly progressive clinical course. Knowledge of the natural history of INAD may serve as a resource for healthcare providers to develop a targeted care plan and may facilitate the design of clinical trials to treat this disease.

scholarly journals The Natural History of Infantile Neuroaxonal Dystrophy

2020 ◽  
Author(s):  
Fadie D Altuame ◽  
Gretchen Foskett ◽  
Paldeep Atwal ◽  
Sarah Endemann ◽  
Mark Midei ◽  
...  
Keyword(s):  
Natural History ◽  
Neurodegenerative Disorder ◽  
Gastrointestinal Disease ◽  
Cerebellar Atrophy ◽  
Neuroaxonal Dystrophy ◽  
Fine Motor ◽  
Speech Impairment ◽  
Infantile Neuroaxonal Dystrophy ◽  
Significant Difference ◽  
History Of

Abstract Background Infantile neuroaxonal dystrophy (INAD) is a rapidly progressive neurodegenerative disorder of early onset causing premature death. It results from biallelic pathogenic variants in PLA2G6 , which encodes a calcium‐independent phospholipase A2. Objective We aim to outline the natural history of INAD and provide a comprehensive description of its clinical, radiological, laboratory, and molecular findings. Materials and Methods We comprehensively analyzed the charts of 28 patients: 16 patients from Riyadh, Saudi Arabia, 8 patients from North and South America and 4 patients from Europe with a molecularly confirmed diagnosis of PLA2G6 ‐associated neurodegeneration (PLAN) and a clinical history consistent with INAD. Results In our cohort, speech impairment and loss of gross motor milestones were the earliest signs of the disease. As the disease progressed, loss of fine motor milestones and bulbar dysfunction were observed. Temporo-frontal function was among the last of the milestones to be lost. Appendicular spastic hypertonia, axial hypotonia, and hyperreflexia were common neurological findings. Other common clinical findings include nystagmus (60.7%), seizures (42.9%), gastrointestinal disease (42.9%), skeletal deformities (35.7%), and strabismus (28.6%). Cerebellar atrophy and elevations in serum AST and LDH levels were consistent features of INAD. There was a statistically significant difference when comparing patients with non-sense/truncating variants compared with missense/in-frame deletions in the time of initial concern (p = 0.04), initial loss of language (p = 0.001), initial loss of fine motor skills (p = 0.009), and initial loss of bulbar skills (p = 0.007). Conclusion INAD is an ultra-rare neurodegenerative disorder that presents in early childhood, with a relentlessly progressive clinical course. Knowledge of the natural history of INAD may serve as a resource for healthcare providers to develop a targeted care plan and may facilitate the design of clinical trials to treat this disease.

scholarly journals The natural history of infantile neuroaxonal dystrophy

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Fadie D. Altuame ◽  
Gretchen Foskett ◽  
Paldeep S. Atwal ◽  
Sarah Endemann ◽  
Mark Midei ◽  
...  
Keyword(s):  
Natural History ◽  
Neuroaxonal Dystrophy ◽  
Infantile Neuroaxonal Dystrophy ◽  
History Of

Cardiac transthyretin wild-type amyloidosis (ATTRwt): a prospective study of 400 patients followed at the Italian referral center

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Milani ◽  
L Obici ◽  
R Mussinelli ◽  
M Basset ◽  
G Manfrinato ◽  
...  
Keyword(s):  
Natural History ◽  
Median Survival ◽  
Troponin I ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Wild Type ◽  
Staging Systems ◽  
Significant Difference ◽  
History Of

Abstract Background Cardiac wild type transthyretin (ATTRwt) amyloidosis, formerly known as senile systemic amyloidosis, is an increasingly recognized, progressive, and fatal cardiomyopathy. Two biomarkers staging systems were proposed based on NT-proBNP (in both cases) and troponin or estimated glomerular filtration rate, that are able to predict survival in this population. The availability of novel effective treatments requires large studies to describe the natural history of the disease in different populations. Objective To describe the natural history of the disease in a large, prospective, national series. Methods Starting in 2007, we protocolized data collection in all the patients diagnosed at our center (n=400 up to 7/2019). Results The referrals to our center increased over time: 5 cases (1%) between 2007–2009, 33 (9%) in 2010–2012, 90 (22%) in 2013–2015 and 272 (68%) in 2016–2019. Median age was 76 years [interquartile range (IQR): 71–80 years] and 372 patients (93%) were males. One hundred and seventy-three (43%) had atrial fibrillation, 63 (15%) had a history of ischemic cardiomyopathy and 64 (15%) underwent pacemaker or ICD implantation. NYHA class was I in 58 subjects (16%), II in 225 (63%) and III in 74 (21%). Median NT-proBNP was 3064 ng/L (IQR: 1817–5579 ng/L), troponin I 0.096 ng/mL (IQR: 0.063–0.158 ng/mL), eGFR 62 mL/min (IQR: 50–78 mL/min). Median IVS was 17 mm (IQR: 15–19 mm), PW 16 mm (IQR: 14–18 mm) and EF 53% (IQR: 45–57%). One-hundred and forty-eight subjects (37%) had a concomitant monoclonal component in serum and/or urine and/or an abnormal free light chain ratio. In these patients, the diagnosis was confirmed by immunoelectron microscopy or mass spectrometry. In 252 (63%) the diagnosis was based on bone scintigraphy. DNA analysis for amyloidogenic mutations in transthyretin and apolipoprotein A-I genes was negative in all subjects. The median survival of the whole cohort was 59 months. The Mayo Clinic staging based on NT-proBNP (cutoff: 3000 ng/L) and troponin I (cutoff: 0.1 ng/mL) discriminated 3 different groups [stage I: 131 (35%), stage II: 123 (32%) and stage III: 127 (33%)] with different survival between stage I and II (median 86 vs. 81 months, P=0.04) and between stage II and III (median 81 vs. 62 months, P<0.001). The UK staging system (NT-proBNP 3000 ng/L and eGFR 45 mL/min), discriminated three groups [stage I: 170 (45%), stage II: 165 (43%) and stage III: 45 (12%)] with a significant difference in survival: between stage I and stage II (86 vs. 52 months, P<0.001) and between stage II and stage III (median survival 52 vs. 33 months, P=0.045). Conclusions This is one of the largest series of patients with cardiac ATTRwt reported so far. Referrals and diagnoses increased exponentially in recent years, One-third of patients has a concomitant monoclonal gammopathy and needed tissue typing. Both the current staging systems offered good discrimination of staging and were validated in our independent cohort. Funding Acknowledgement Type of funding source: None

Siblings with Infantile Neuroaxonal Dystrophy

2020 ◽  
Author(s):  
Pulkit Agarwal ◽  
Jyotindra Narayan Goswami
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Febrile Illness ◽  
Neuroaxonal Dystrophy ◽  
Infantile Neuroaxonal Dystrophy ◽  
Motor Delay ◽  
Developmental Regression ◽  
Female Sibling ◽  
History Of

AbstractA 2 years 3 months male toddler with motor delay and his female sibling with history of marked global developmental regression following an intercurrent febrile illness were both noted to have phospholipase A2G6 (PLA2G6) mutation, confirming the diagnosis of infantile neuroaxonal dystrophy (INAD). This case report attempts to familiarize readers with the pleomorphic presentation of INAD and the role of early clinical identification, examination, and prompt genetic testing in establishing a diagnosis.

Su1246 Temporal Trends and Natural History of Eosinophils-Related Gastrointestinal Disease in Asia

2013 ◽  
Vol 144 (5) ◽  
pp. S-438 ◽  
Author(s):  
So Yoon Yoon ◽  
Hye-Kyung Jung ◽  
So-Young Ahn ◽  
Yoon Pyo Lee ◽  
Hye In Kim ◽  
...  
Keyword(s):  
Natural History ◽  
Gastrointestinal Disease ◽  
Temporal Trends ◽  
History Of

Novel Mutation in PLA2G6 Gene in a Patient with Infantile Neuroaxonal Dystrophy

2016 ◽  
Vol 15 (02) ◽  
pp. 073-075 ◽  
Author(s):  
Aravindhan Veerapandiyan ◽  
Amit Chaudhari ◽  
Akilandeswari Aravindhan ◽  
Caroline Hayes-Rosen
Keyword(s):  
Autosomal Recessive ◽  
Novel Mutation ◽  
Cerebellar Atrophy ◽  
Autosomal Recessive Disorder ◽  
Neuroaxonal Dystrophy ◽  
Infantile Neuroaxonal Dystrophy ◽  
Group Vi ◽  
Calcium Independent Phospholipase A2 ◽  
Bulbar Dysfunction ◽  
Spastic Quadriparesis

AbstractInfantile neuroaxonal dystrophy (INAD) is an autosomal recessive disorder that causes psychomotor regression. Clinicopathological features include truncal hypotonia followed by spastic quadriparesis, strabismus, nystagmus, cerebellar ataxia, bulbar dysfunction, and cerebellar atrophy. INAD is associated with a variety of mutations in the PLA2G6 gene that encodes the group VI calcium-independent phospholipase A2 protein which is important in cell membrane homeostasis. Defects in this protein cause axonal dystrophy. We report a 2-year-old boy with INAD who was found to have a novel deletion c.1019_1025del7 leading to a frame shift in the PLA2G6 gene. We suggest that this change may be an addition to the array of mutations causing INAD.

Anesthesia for patients with pantothenate-kinase-associated neurodegeneration (Hallervorden-Spatz disease) – a literature review

2006 ◽  
Vol 18 (3-4) ◽  
pp. 168-172 ◽  
Author(s):  
Jochen Hinkelbein ◽  
Armin Kalenka ◽  
Markus Alb
Keyword(s):  
Neurodegenerative Diseases ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Anesthetic Management ◽  
Neuroaxonal Dystrophy ◽  
Anesthetic Techniques ◽  
Infantile Neuroaxonal Dystrophy ◽  
Pantothenate Kinase ◽  
Anesthetic Complications

Background:Hallervorden-Spatz disease (HSD) is a rare, progressive neurodegenerative disorder; the new and preferred name for HSD is ‘pantothenate-kinase-associated neurodegeneration’ (PKAN). Other suggested names are ‘neurodegeneration with brain iron accumulation type 1’ or ‘infantile neuroaxonal dystrophy’. Patients with PKAN have many complications, which lead to numerous anesthetic management challenges. Reports concerning the anesthetic management of patients with PKAN are very limited.Objective:To determine the anesthetic management and techniques as well as relevant complications for patients with PKAN.Methods:In this study, we review previously published literature regarding the anesthesia-relevant clinical symptoms, the anesthetic management and techniques, and possible complications for this disorder.Results:Only four studies describing the anesthetic management and anesthetic techniques in patients with PKAN were found. Anesthesia-relevant symptoms influence the preanesthetic management (eg difficulties in articulation, dementia), the induction of anesthesia (eg oromandibular rigidity, seizures, dysphagia, aspiration) and the postoperative care (eg respiratory disability).Conclusion:Reports concerning the anesthetic management of patients with PKAN are very limited, possibly as a result of the rareness of the disorder. Like many other patients with neurodegenerative diseases, patients with PKAN have many anesthesia-relevant symptoms, leading to numerous anesthetic management challenges. In general, the anesthetic complications associated with PKAN are usually no different from those associated with other neurodegenerative diseases, and the management of these are usually concordant.

scholarly journals Effect of COVID-19 on the clinical course of diabetic ketoacidosis (DKA) in people with type 1 and type 2 diabetes

2021 ◽  
Vol 10 (4) ◽  
pp. 371-377
Author(s):  
Punith Kempegowda ◽  
Eka Melson ◽  
Agnes Johnson ◽  
Lucy Wallett ◽  
Lucretia Thomas ◽  
...  
Keyword(s):  
Natural History ◽  
Clinical Course ◽  
External Control ◽  
Multi Centre Study ◽  
Significant Difference ◽  
History Of ◽  
Using Data ◽  
Worse Prognosis

Objective COVID-19 in people with diabetes is associated with a disproportionately worse prognosis. DKA is an acute complication of diabetes with a mortality rate of approximately 0.67%. Little is known about the natural history of DKA in the presence of COVID-19. This study aimed to explore the effects of COVID-19 on presentation, clinical course and outcome in patients presenting with DKA. Design Retrospective cohort study. Methods All patients treated for DKA between 1 March 2020 and 30 May 2020 were included. Patients were categorised as COVID-positive or COVID-negative based on the swab test. A pre-COVID group was established using data from 01 March 2019 to 30 May 2019 as external control. Data regarding demographics, diabetes type, pH, bicarbonate, lactate, glucose, DKA duration, complications and outcome were collected. Results A total of 88 DKA episodes were included in this study. There was no significant difference in the severity or duration of DKA between the three groups. COVID-positive T1DM were more hyperglycaemic on admission compared to COVID-negative and pre-COVID patients. There was an over representation of T2DM in COVID-positive patients with DKA than in pre-COVID or COVID-negative groups. Conclusion COVID-19 appears to influence the natural history of DKA differently in T1DM and T2DM. Patients with T1DM and COVID-19 presented with more hyperglycaemia (60 mmol/L (35.9–60.0) vs 31.4 mmol/L (28.0–39.1) vs 24 mmol/L (20.2–33.75), respectively). Patients with T2DM were unusually presenting in DKA when infected with COVID-19 with greater ICU need and higher mortality rates. A collaborative, multi-centre study is needed to provide more definitive results.

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