Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary mitochondrial disorders are a group of clinically variable and heterogeneous inborn errors of metabolism (IEMs), resulting from defects in cellular energy, and can affect every organ system of the body. Clinical presentations vary and may include symptoms of fatigue, skeletal muscle weakness, exercise intolerance, short stature, failure to thrive, blindness, ptosis and ophthalmoplegia, nystagmus, hearing loss, hypoglycemia, diabetes mellitus, learning difficulties, intellectual disability, seizures, stroke-like episodes, spasticity, dystonia, hypotonia, pain, neuropsychiatric symptoms, gastrointestinal reflux, dysmotility, gastrointestinal pseudo-obstruction, cardiomyopathy, cardiac conduction defects, and other endocrine, renal, cardiac, and liver problems. Most phenotypic manifestations are multi-systemic, with presentations varying at different age of onset and may show great variability within members of the same family; making these truly complex IEMs. Most primary mitochondrial diseases are autosomal recessive (AR); but maternally-inherited [from mitochondrial (mt) DNA], autosomal dominant and X-linked inheritance are also known. Mitochondria are unique energy-generating cellular organelles, geared for survival and contain their own unique genetic coding material, a circular piece of mtDNA about 16,000 base pairs in size. Additional nuclear (n)DNA encoded genes maintain mitochondrial biogenesis by supervising mtDNA replication, repair and synthesis, which is modified during increased energy demands or physiological stress. Despite our growing knowledge of the hundreds of genetic etiologies for this group of disorders, diagnosis can also remain elusive due to unique aspects of mitochondrial genetics. Though cure and FDA-approved therapies currently elude these IEMs, and current suggested therapies which include nutritional supplements and vitamins are of questionable efficacy; multi-center, international clinical trials are in progress for primary mitochondrial disorders.
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PMID:Mitochondrial disorders. 3074 Apr 6

Succinic semialdehyde dehydrogenase (SSADH) deficiency is an autosomal recessive disorder of gamma-aminobutyric acid metabolism. Children with SSADH deficiency usually manifest with developmental delay, behavioral symptoms, language dysfunction, seizures, hypotonia, extrapyramidal symptoms, and ataxia. Diagnosis of SSADH deficiency is established by an abnormal urine organic acid pattern, including increased excretion of 4-hydroxybutyric acid and the identification of biallelic pathogenic variants in aldehyde dehydrogenase 5 family, member A 1 (ALDH5A1) gene. Here, we describe a 15-month-old girl with SSADH deficiency presenting with developmental delay, language deficits, and acute-onset right hemiparesis, following recovery from a diarrheal illness. Brain magnetic resonance imaging revealed hyperintense signal changes involving the left globus pallidus in T2-weighted images with restriction of diffusion in the diffusion-weighted images. Increased excretion of 4-hydroxybutyric acid, threo-4,5-dihydroxyhexanoic acid lactone and erythro-4,5-dihydroxyhexanoic acid lactone was detected by urine organic acid analysis and a diagnosis of SSADH deficiency was confirmed by the identification of homozygous pathogenic variant in ALDH5A1. Stroke mimic is a novel presentation in our patient with SSADH deficiency. She was initiated on treatment with vigabatrin and has shown developmental gains with the recovery of right hemiparesis. Follow-up neuroimaging shows near complete resolution of signal changes in the left globus pallidus, while there was subtle hyperintensity in the right globus pallidus. The phenotypic spectrum of SSADH deficiency is widely expanding, and this disorder should be considered in the differential diagnosis of children with metabolic stroke.
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PMID:Metabolic Stroke: A Novel Presentation in a Child with Succinic Semialdehyde Dehydrogenase Deficiency. 3205 32


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