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Succinic semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric aciduria or gamma-hydroxybutyric aciduria, is a rare autosomal recessive disorder of the degradation pathway of the inhibitory neurotransmitter γ-aminobutyric acid, or GABA. The disorder has been identified in approximately 350 families, with a significant proportion being consanguineous families. The first case was identified in 1981 and published in a Dutch clinical chemistry journal that highlighted a patient that suffered from a number of neurological conditions such as delayed intellectual, motor, speech, and language as the most common manifestations. Later cases reported in the early 1990s began to show that hypotonia, hyporeflexia, seizures, and a nonprogressive ataxia were frequent clinical features as well. SSADH deficiency is caused by an enzyme deficiency in GABA degradation. Under normal conditions, SSADH works with the enzyme GABA transaminase to convert GABA to succinic acid. Succinic acid can then be utilized for energy production via the Krebs cycle. However, because of the deficiency, the final intermediate of the GABA degradation pathway, succinic semialdehyde, accumulates and cannot be oxidized to succinic acid and is therefore reduced to gamma-hydroxybutyric acid (GHB) by gamma-hydroxybutyric dehydrogenase. This causes elevations in GHB and is believed to be the trademark of this disorder and cause for the neurological manifestations seen.〔 == Signs and symptoms == The symptoms of SSADH deficiency fall into three primary categories: neurological, psychiatric, and ocular. The most constant features seen are developmental delay, hypotonia, and mental retardation. Nearly half of patients seen manifest ataxia, behavior problems, seizures, and hyporeflexia.〔 The age of onset ranges from newborn period to 25 years. Problems unique to neonates can include prematurity, lethargy, decreased sucking, respiratory difficulty and hypoglycemia. Gastrointestinal symptoms have been seen primarily in this population and are usually related to increased feeding. Ocular problems related to the disorder include strabismus, nystagmus, retinitis, disc pallor, and oculomotor apraxia. Nearly half of the patients with SSADH deficiency have seizures. These include absence, tonic clonic, and convulsive status epilepticus. It is unclear whether decreased levels of GABA or elevated levels of GHB are responsible for these seizures but alterations in these neurotransmitters and their receptor binding or neurotransmitter transport is hypothesized to play a role in the pathogenesis of the seizures in this population. Symptoms associated with SSADH may be mild, moderate or severe and often vary greatly from case to case. The symptoms of SSADH are caused by the accumulation of GHB in the brain and include the following manifestations (Defined as: common, > 70% of patients; frequent 30-70% of patients;unusual, < 30% of patients): Common manifestations include: * Delayed gross motor development * Delayed mental development * Delayed fine motor skill development * Delayed speech and language development * Hypotonia Frequent manifestations include: * Seizures * Hyporeflexia * Ataxia * Behavioral problems * Hyperkinesis Unusual manifestations include: * Neonatal problems * EEG abnormalities * Psychoses * MRI or X-ray computed tomography abnormalities * Oculomotor apraxia * Microcephaly * Macrocephaly * Hyperreflexia * Somnolence * Autistic features * Choreoathetosis * Myopathy 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Succinic semialdehyde dehydrogenase deficiency」の詳細全文を読む スポンサード リンク
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