Apart from the abovementioned disorders, there are several other diseases that are associated with mtDNA depletion with multiorgan presentation. [heighpubs.org]

Although Alpers-Huttenlocher syndrome has a restricted neuro-hepatic presentation, mutations in this same gene can result in a broad range of clinical presentations that involve not only the brain and liver, but the rest of the central and peripheral [medlink.com]

The reasons for the difference in presentation onset and severity of disease are unclear. [dovepress.com]

Haplotype data for each patient is presented in Table 2. [journals.plos.org]

Reflexes were present and symmetrical. She was just able to walk with a stick and required 1 person's assistance. Mitochondrial disease was suspected, and she underwent a muscle biopsy. [ng.neurology.org]

• Episodic Abdominal Pain

  abdominal pain and/or distention, and diarrhea), cachexia, ptosis/ophthalmoplegia or ophthal-moparesis, leukoencephalopathy, demyelinating peripheral neuropathy, and symmetric and distal weakness more prominently affecting the lower extremities. [heighpubs.org]

• Recurrent Vomiting

  The most common initial symptoms are generalized tonic-clonic seizures, recurrent headaches, anorexia, and recurrent vomiting. Seizures are often associated with stroke-like episodes of transient hemiparesis or cortical blindness. [heighpubs.org]

• Proximal Muscle Weakness

  CPEO is sometimes complicated by mild proximal muscle weakness and dysphagia, and can be considered to lie on a spectrum of disease from pure CPEO to Kearns-Sayre syndrome phenotype. [heighpubs.org]

• Recurrent Headache

  The most common initial symptoms are generalized tonic-clonic seizures, recurrent headaches, anorexia, and recurrent vomiting. Seizures are often associated with stroke-like episodes of transient hemiparesis or cortical blindness. [heighpubs.org]

• Dysautonomia

  Systemic features include cardiomyopathy, gastrointestinal and bladder dysautonomia, hepatic dysfunction, and gonadal failure and other endocrinopathies (39). [medlink.com]

• Onset at Age <20

  Some individuals with CPEO (<20%) have a pathogenic single-nucleotide variant of mtDNA (e.g., m.3243A>G) [48]. f) Kearns-Sayre syndrome (KSS): A mtDNA deletion syndrome, is a multisystem disorder defined by the triad of onset before age 20 years, pigmentary [heighpubs.org]

Diagnostic workup Genetic testing. Sequencing POLG should be performed if Alpers-Huttenlocher syndrome is suspected. [medlink.com]

• Lymphopenia

  […] involve the heart (hypertrophic cardiomyopathy, congenital heart malformations, arrhythmias), liver (mildly elevated transaminases), eyes (cataract, strabismus, nystagmus, optic atrophy), hearing (sensorineural hearing loss), and bone marrow (neutropenia, lymphopenia [heighpubs.org]

Approaches to treatment. Neurotherapeutics. 2008;5:558–68. [ncbi.nlm.nih.gov]

Management Treatment of manifestations. [medlink.com]

Unfortunately, treatment of AHS is limited to symptom management and supportive care. It is essential to emphasize and address quality-of-life issues and the intensity of treatment modalities. [dovepress.com]

Her seizures were suprarefractory to treatment, despite receiving a combination of phenytoin, levetiracetam, clonazepam, propofol, midazolam, and pulse methylprednisolone. [ng.neurology.org]

The liver disease in Alpers-Huttenlocher syndrome can be brought on or made worse by valproic acid, a common treatment for seizures. Most POLG gene mutations change single protein building blocks (amino acids) in the alpha subunit of pol γ. [medlineplus.gov]

Prognosis and complications The disease progression is variable in both timing and rapidity. [medlink.com]

Her older brother had similar ocular symptoms and carried a diagnosis of neuropathy; both of uncertain etiology too. Before the first visit with us, she had undergone several tests since the symptom onset that we have summarized here. [frontiersin.org]

ACM includes arrhythmogenic right ventricular cardiomyopathy and may overlap with other cardiomyopathy phenotypes.1 Although a genetic etiology is often suspected, causal mutations are not identified in up to 50% of patients with inherited ACM.1 In this [ahajournals.org]

Our patient's initial presentation of a progressive cerebellar ataxia plus other neurologic features including external ophthalmoplegia and myoclonus is highly suggestive of a mitochondrial etiology. [ng.neurology.org]

These data provided the full pathophysiology of the phenotype, including the identification of the genetic etiology and the physiologic changes of reduced mtDNA content inducing mtDNA depletion. [medlink.com]

[…] detectable by assay.9 Then, in 2004 Naviaux and Nguyen described pathological mutations in POLG responsible for the phenotype of AHS.10 These latter studies closed the loop of neuropathological, clinical phenotype, biochemical abnormality, and genetic etiology [dovepress.com]

Epidemiology The true prevalence of Alpers-Huttenlocher syndrome is unknown. Due to high mortality and early death, epidemiology parameters of incidence and prevalence are not informative. [medlink.com]

The pathophysiology of the disorder results from the depletion of mtDNA and is influenced by multiple environmental factors, in particular viral infections and medication exposure. [dovepress.com]

Hints as to the pathophysiology of this disorder did not exist until 1972, when ultrastructural studies showed giant and disorganized mitochondria in neurons from patients with the disorder (67). [medlink.com]

Early recognition of liver dysfunction and discontinuation of valproate may prevent the progression to fulminant liver failure (51; 88). [medlink.com]