Inherited Metabolic Causes of Stroke in Children: Mechanisms, Types, and Management

Tabarki, Brahim; Hakami, Wejdan; Alkhuraish, Nader; Graies-Tlili, Kalthoum; Nashabat, Marwan; Alfadhel, Majid

doi:10.3389/fneur.2021.633119

Cited by 10 publications

(12 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Clinical features include a tall slender habitus, muscle weakness, and abnormalities of the eyes (lens dislocations), skeletal system (scoliosis, genu varus, pectus excavatum), nervous system (mental retardation), and vascular system (arteriopathies and fibrosis of arteries). 2 Homocystinuria with an initial clinical presentation of stroke in childhood, as reported in this case, is very rare. 1…”

Section: Introductionmentioning

confidence: 68%

Angiopathy and Stroke Associated with Homocystinuria in Childhood

Demartini

Neves

Carmo

et al. 2022

Vasc Endovascular Surg

View full text Add to dashboard Cite

A previously healthy 13 year-old boy presented with acute-onset headaches, aphasia and right-sided hemiparesis. Imaging showed cerebral ischemic infarction due to bilateral carotid occlusion, and investigation for stroke etiology diagnosed homocystinuria. Homocystinuria is an autosomal recessive condition that affects the metabolism of the amino acid methionine due to an enzyme deficiency. This disorder involves multiple organs systems, and complications include thromboembolic events, ectopia lentis, mental retardation, and skeletal abnormalities. The early diagnosis and treatment of hyperhomocystinemia can significantly improve outcomes. Therefore, metabolic screening for homocystinuria is strongly recommended for children presenting with stroke.

show abstract

Section: Introductionmentioning

confidence: 68%

Angiopathy and Stroke Associated with Homocystinuria in Childhood

Demartini

Neves

Carmo

et al. 2022

Vasc Endovascular Surg

View full text Add to dashboard Cite

show abstract

“…Often the first symptom is myoclonus. Additionally, we observed generalized epilepsy, ataxia, weakness, exercise intolerance and dementia [ 34 , 35 , 36 , 37 ]. Onset can occur from childhood and adulthood.…”

Section: Resultsmentioning

confidence: 99%

“…Common signs are ptosis, hearing loss, optic atrophy, cardiomyopathy, Wolff–Parkinson–White (WPW) syndrome and peripheral neuropathy. Pigmentary retinopathy and optic nerve neuropathy can also occur [ 34 , 35 , 36 , 37 ]. Most cases have the common mutation m8344A > G in the MTTK gene, but MERRF has also been linked to other mtDNA point mutations [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

“…The features of various neurometabolic disorders characterized by the occurrence of SLEs include genetic and molecular basis, clinical manifestations, MRI and EEG results, onset and prevalence and treatment methods ( Table 1 ) [ 2 , 3 , 4 , 7 , 8 , 9 , 11 , 13 , 14 , 15 , 16 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , …”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Stroke-like Episodes in Inherited Neurometabolic Disorders

2022

View full text Add to dashboard Cite

Stroke-like episodes (SLEs) are significant clinical manifestations of metabolic disorders affecting the central nervous system. Morphological equivalents presented in neuroimaging procedures are described as stroke-like lesions (SLLs). It is crucial to distinguish SLEs from cerebral infarction or intracerebral hemorrhage, mainly due to the variety in management. Another significant issue to underline is the meaning of the main pathogenetic hypotheses in the development of SLEs. The diagnostic process is based on the patient’s medical history, physical and neurological examination, neuroimaging techniques and laboratory and genetic testing. Implementation of treatment is generally symptomatic and includes L-arginine supplementation and adequate antiepileptic management. The main aim of the current review was to summarize the basic and actual knowledge about the occurrence of SLEs in various inherited neurometabolic disorders, discuss the possible pathomechanism of their development, underline the role of neuroimaging in the detection of SLLs and identification of the electroencephalographic patterns as well as histological abnormalities in inherited disorders of metabolism.

show abstract

“…In about four out of five patients, MELAS syndrome is connected with a point mutation in the MTTL1 gene that encodes tRNA-Leu (m.3243A>G). Other individuals that are diagnosed with a MELAS have other variants of MTTL1 or mutations in some other mitochondrial genes [97]. Considering potential therapeutic options, the administration of L-arginine and L-citrulline could elevate nitric oxide (NO) production, thus having favorable benefits for patient care with MELAS [98,99].…”

Section: Mitochondrial Inheritancementioning

confidence: 99%

The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options

Janković

Petrović²,

Novaković

et al. 2022

IJMS

View full text Add to dashboard Cite

Strokes within pediatric populations are considered to be the 10th leading cause of death in the United States of America, with over half of such events occurring in children younger than one year of life. The multifactorial etiopathology that has an influence on stroke development and occurrence signify the importance of the timely recognition of both modifiable and non-modifiable factors for adequate diagnostic and treatment approaches. The early recognition of a stroke and stroke risk in children has the potential to advance the application of neuroprotective, thrombolytic, and antithrombotic interventions and rehabilitation strategies to the earliest possible timepoints after the onset of a stroke, improving the outcomes and quality of life for affected children and their families. The recent development of molecular genetic methods has greatly facilitated the analysis and diagnosis of single-gene disorders. In this review, the most significant single gene disorders associated with pediatric stroke are presented, along with specific therapeutic options whenever they exist. Besides monogenic disorders that may present with stroke as a first symptom, genetic polymorphisms may contribute to the risk of pediatric and perinatal stroke. The most frequently studied genetic risk factors are several common polymorphisms in genes associated with thrombophilia; these genes code for proteins that are part of the coagulation cascade, fibrolysis, homocystein metabolism, lipid metabolism, or platelets. Single polymorphism frequencies may not be sufficient to completely explain the stroke causality and an analysis of several genotype combinations is a more promising approach. The recent steps forward in our understanding of the disorders underlying strokes has given us a next generation of therapeutics and therapeutic targets by which to improve stroke survival, protect or rebuild neuronal connections in the brain, and enhance neural function. Advances in DNA sequencing and the development of new tools to correct human gene mutations have brought genetic analysis and gene therapy into the focus of investigations for new therapeutic options for stroke patients.

show abstract

Inherited Metabolic Causes of Stroke in Children: Mechanisms, Types, and Management

Cited by 10 publications

References 42 publications

Angiopathy and Stroke Associated with Homocystinuria in Childhood

Angiopathy and Stroke Associated with Homocystinuria in Childhood

Stroke-like Episodes in Inherited Neurometabolic Disorders

The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options

Contact Info

Product

Resources

About