4-Hydroxybutyric aciduria: Further clinical heterogeneity in a new case

Onkenhout, W.; Maaswinkel-Mooij, P. D.; Poorthuis, B. J. H. M.

doi:10.1007/bf01958280

Cited by 15 publications

(6 citation statements)

References 11 publications

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“…Case ascertainment dating back to the initial report of gamma-hydroxybutyric aciduria identified 91 unique patients with clinical details provided (Aoshima et al 2002;Bekri et al 2004;Brown et al 1987;Dayan et al 2006;Deng et al 2011;Divry et al 1983;Escalera et al 2010;Gogou et al 2016;Haan et al 1985; Ishiguro et al 2001; Jakobs et al 1981;Jiang et al 2013;Kratz 2009;Kwok et al 2012;Lemes et al 2006;Li et al 2015;Lin et al 2015;Liu et al 2016;Neu et al 2002;Niemi et al 2014;O'Rourke et al 2010;Onkenhout et al 1989;Pearl et al 2003;Peters et al 1999;Puttmann et al 2013;Racaru et al 2010;Rashed et al 1994;Rating et al 1984;Saronwala et al 2008;Spilioti et al 2013;Tay et al 2015;Wang et al 2016;Yamakawa et al 2012;Zhao et al 2003;Ziyeh et al 2002). We furthermore identified 91 additional subjects with confirmed SSADH deficiency in our database published in aggregate (Parviz et al 2014).…”

Section: Case Reports and Resultsmentioning

confidence: 99%

Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

et al. 2016

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The incidence of succinic semialdehyde dehydrogenase (SSADH) deficiency, an autosomal recessive inherited disorder of GABA degradation, is unknown. Upon a recent diagnosis of a new family of affected fraternal twins from the Punjabi ethnic group of India, case ascertainment from the literature and our database was done to determine the number of confirmed cases along with their geographic distribution. The probands presented with global developmental delay, infantile onset epilepsy, and a persistent neurodevelopmental disorder upon diagnosis at 10 years of age with intellectual disability, expressive aphasia, and behavioral problems most prominent for hyperactivity. Gamma-hydroxybutyric aciduria and homozygous ALDH5A1 c.608C>T; p.Pro203Leu mutations were confirmed. Identification of all available individual cases with clinical details available including geographic or ethnic origin revealed 182 patients from 40 countries, with the largest number of patients reported from the USA (24%), Turkey (10%), China (7%), Saudi Arabia (6%), and Germany (5%). This study provides an accounting of all published cases of confirmed SSADH deficiency and provides data useful in planning further studies of this rare inborn error of metabolism.

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Section: Case Reports and Resultsmentioning

confidence: 99%

Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

et al. 2016

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“…We also report a range of EEG findings based on a literature review capturing 25 published cases with EEG data available [11][12][13][14][15][16]18,19 and combined with 9 patients from our cohort (see table 2). Abnormalities include generalized and focal epileptiform discharges, photosensitivity, background slowing, and sleep spindle asynchrony.…”

Section: Resultsmentioning

confidence: 99%

“…Abnormalities include generalized and focal epileptiform discharges, photosensitivity, background slowing, and sleep spindle asynchrony. [11][12][13][14][15][16][17][18][19]21 These revealed T2 hyperintensities in multiple regions, most commonly of the globus pallidus (see table 2). The explanation for epilepsy in nearly half of SSADH-deficient patients is unclear.…”

Section: Resultsmentioning

confidence: 99%

Clinical spectrum of succinic semialdehyde dehydrogenase deficiency

Pearl¹,

Gibson²,

Acosta³

et al. 2003

Neurology

190

158

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Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting CNS gamma-aminobutyric acid (GABA) degradation. SSADH, in conjunction with GABA transaminase, converts GABA to succinate. In the absence of SSADH, GABA is converted to 4-OH-butyrate. The presence of 4-OH-butyrate, a highly volatile compound, may be undetected on routine organic acid analysis. Urine organic acid testing was modified at the authors' institution in 1999 to screen for the excretion of 4-OH-butyrate by selective ion monitoring gas chromatography-mass spectrometry in addition to total ion chromatography. Since then, five patients with 4-hydroxybutyric aciduria have been identified. The authors add the clinical, neuroimaging, and EEG findings from a new cohort of patients to 51 patients reported in the literature with clinical details. Ages ranged from 1 to 21 years at diagnosis. Clinical findings include mild-moderate mental retardation, disproportionate language dysfunction, hypotonia, hyporeflexia, autistic behaviors, seizures, and hallucinations. Brain MRI performed in five patients at the authors' institution revealed symmetric increased T2 signal in the globus pallidi. SSADH deficiency is an under-recognized, potentially manageable neurometabolic disorder. Urine organic acid analysis should include a sensitive method for the detection of 4-hydroxybutyrate and should be obtained from patients with mental retardation or neuropsychiatric disturbance of unknown etiology.

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“…Electroencephalographic studies have disclosed a variety of background abnormalities and epileptiform features. On the basis of a review of 35 cases having electroencephalographic data available, we reported spike discharges (focal and generalized) in 8 of 34 patients (24%), photoparoxysmal response in 1 patient, background slowing in 8 patients, sleep spindle asynchrony in 1 adult patient, and lack of stage rapid eye movement on one overnight study 4, 10, 12–15, 22, 23, 25. There were normal recordings in 16 patients (46%).…”

Section: Neurophysiologymentioning

confidence: 99%

Succinic semialdehyde dehydrogenase deficiency in children and adults

Pearl¹,

Novotny²,

Acosta³

et al. 2003

Ann Neurol.

119

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Succinic semialdehyde dehydrogenase deficiency is a rare disorder of the degradation pathway of gamma-aminobutyric acid. The disorder is detected when 4-hydroxybutyric aciduria is present on urine organic acid analysis, and is subsequently confirmed by enzyme measurement on leucocytes. The disorder has been identified in approximately 350 individuals worldwide. We review the clinical features in 60 patients. The most common characteristics are developmental delay maximally involving expressive language, hypotonia, mental retardation, ataxia, and behavioral problems. Seizures occur in approximately half of patients, and include tonic-clonic, absence, and myoclonic seizures, including status epilepticus. Electroencephalographic findings are background slowing and generalized and focal epileptiform discharges. Magnetic resonance imaging typically reveals increased T2-weighted signal of the globus pallidus bilaterally, with variable involvement of white matter and the cerebellar dentate nucleus. Preliminary human cerebrospinal fluid measurements are consistent with neurometabolic aberrations documented in the murine animal model, with elevations in gamma-aminobutyric acid, gamma-hydroxybutyrate, and homocarnosine, and low glutamine. Succinic semialdehyde dehydrogenase deficiency may be an underrecognized neurometabolic disorder with a nonspecific and wide phenotypic spectrum, and carries implications for a comprehensive fundamental understanding of interrelations between multiple neurotransmitter systems.

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4-Hydroxybutyric aciduria: Further clinical heterogeneity in a new case

Cited by 15 publications

References 11 publications

Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

Clinical spectrum of succinic semialdehyde dehydrogenase deficiency

Succinic semialdehyde dehydrogenase deficiency in children and adults

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