The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): Case reports of 23 new patients

K. Michael Gibson, Ernst Christensen, Cornelis Jakobs, Brian Fowler, Michael A. Clarke, Gerhard Hammersen, Klaus Raab, Joyce Kobori, Allie Moosa, Brigitte Vollmer, Eva Rossier, A. Kimberly Iafolla, Dietrich Matern, Oebele F. Brouwer, Janice Finkelstein, Fuat Aksu, Hans Peter Weber, Jan A J M Bakkeren, Fons J M Gabreels, Daniel BluestoneTodd F. Barron, Pierre Beauvais, Daniel Rabier, Cesar Santos, Richard Umansky, Willy Lehnert

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Objectives. To further define the clinical spectrum of the disease for pediatric and metabolic specialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde dehydrogenase (SSADH) deficiency in the differential diagnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative organic acid analysis in such patients. Patients. The clinical features of 23 patients (20 families) with SSADH deficiency (4- hydroxybutyric acid-uria) are presented. The age at diagnosis ranged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families. Outcome Measurements. The following abnormalities were observed (frequency in 23 patients): motor delay, including fine-motor skills, 78%; language delay, 78%; hypotonia, 74%; mental delay, 74%; seizures, 48%; decreased or absent reflexes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; neonatal problems, 26%; and electroencephalographic abnormalities, 26%. Associated findings included psychoses, cranial magnetic resonance or computed tomographic abnormalities, and ocular problems in 22% or less of patients. Therapy with vigabatrin proved beneficial to varying degrees in 35% of the patients. Normal early development was noted in 30% of patients. Conclusions. Our data imply that two groups of patients with SSADH deficiency exist, differentiated by the course of early development. Our recommendation would be that accurate, quantitative organic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, motor, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis can be confirmed by determination of enzyme activity in white cells from whole blood. We think that increased use of organic acid determination will lead to increased diagnosis of SSADH deficiency and a more accurate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metabolic and clinical profiles of SSADH deficiency.

Original languageEnglish (US)
Pages (from-to)567-574
Number of pages8
JournalPediatrics
Volume99
Issue number4
StatePublished - Apr 1997
Externally publishedYes

Fingerprint

Phenotype
Language Development Disorders
Abnormal Reflexes
Muscle Hypotonia
Acids
succinic semialdehyde dehydrogenase deficiency
Pediatrics
Vigabatrin
Hyperkinesis
Consanguinity
Motor Skills
Metabolome
Metabolic Diseases
Ataxia
Intellectual Disability
Psychotic Disorders
Seizures
Leukocytes
Differential Diagnosis
Magnetic Resonance Spectroscopy

Keywords

  • 4- hydroxybutyric aciduria
  • ataxia
  • hypotonia
  • mental retardation
  • succinic semialdehyde dehydrogenase deficiency

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Gibson, K. M., Christensen, E., Jakobs, C., Fowler, B., Clarke, M. A., Hammersen, G., ... Lehnert, W. (1997). The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): Case reports of 23 new patients. Pediatrics, 99(4), 567-574.

The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria) : Case reports of 23 new patients. / Gibson, K. Michael; Christensen, Ernst; Jakobs, Cornelis; Fowler, Brian; Clarke, Michael A.; Hammersen, Gerhard; Raab, Klaus; Kobori, Joyce; Moosa, Allie; Vollmer, Brigitte; Rossier, Eva; Iafolla, A. Kimberly; Matern, Dietrich; Brouwer, Oebele F.; Finkelstein, Janice; Aksu, Fuat; Weber, Hans Peter; Bakkeren, Jan A J M; Gabreels, Fons J M; Bluestone, Daniel; Barron, Todd F.; Beauvais, Pierre; Rabier, Daniel; Santos, Cesar; Umansky, Richard; Lehnert, Willy.

In: Pediatrics, Vol. 99, No. 4, 04.1997, p. 567-574.

Research output: Contribution to journalArticle

Gibson, KM, Christensen, E, Jakobs, C, Fowler, B, Clarke, MA, Hammersen, G, Raab, K, Kobori, J, Moosa, A, Vollmer, B, Rossier, E, Iafolla, AK, Matern, D, Brouwer, OF, Finkelstein, J, Aksu, F, Weber, HP, Bakkeren, JAJM, Gabreels, FJM, Bluestone, D, Barron, TF, Beauvais, P, Rabier, D, Santos, C, Umansky, R & Lehnert, W 1997, 'The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): Case reports of 23 new patients', Pediatrics, vol. 99, no. 4, pp. 567-574.
Gibson KM, Christensen E, Jakobs C, Fowler B, Clarke MA, Hammersen G et al. The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): Case reports of 23 new patients. Pediatrics. 1997 Apr;99(4):567-574.
Gibson, K. Michael ; Christensen, Ernst ; Jakobs, Cornelis ; Fowler, Brian ; Clarke, Michael A. ; Hammersen, Gerhard ; Raab, Klaus ; Kobori, Joyce ; Moosa, Allie ; Vollmer, Brigitte ; Rossier, Eva ; Iafolla, A. Kimberly ; Matern, Dietrich ; Brouwer, Oebele F. ; Finkelstein, Janice ; Aksu, Fuat ; Weber, Hans Peter ; Bakkeren, Jan A J M ; Gabreels, Fons J M ; Bluestone, Daniel ; Barron, Todd F. ; Beauvais, Pierre ; Rabier, Daniel ; Santos, Cesar ; Umansky, Richard ; Lehnert, Willy. / The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria) : Case reports of 23 new patients. In: Pediatrics. 1997 ; Vol. 99, No. 4. pp. 567-574.
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T1 - The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria)

T2 - Case reports of 23 new patients

AU - Gibson, K. Michael

AU - Christensen, Ernst

AU - Jakobs, Cornelis

AU - Fowler, Brian

AU - Clarke, Michael A.

AU - Hammersen, Gerhard

AU - Raab, Klaus

AU - Kobori, Joyce

AU - Moosa, Allie

AU - Vollmer, Brigitte

AU - Rossier, Eva

AU - Iafolla, A. Kimberly

AU - Matern, Dietrich

AU - Brouwer, Oebele F.

AU - Finkelstein, Janice

AU - Aksu, Fuat

AU - Weber, Hans Peter

AU - Bakkeren, Jan A J M

AU - Gabreels, Fons J M

AU - Bluestone, Daniel

AU - Barron, Todd F.

AU - Beauvais, Pierre

AU - Rabier, Daniel

AU - Santos, Cesar

AU - Umansky, Richard

AU - Lehnert, Willy

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N2 - Objectives. To further define the clinical spectrum of the disease for pediatric and metabolic specialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde dehydrogenase (SSADH) deficiency in the differential diagnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative organic acid analysis in such patients. Patients. The clinical features of 23 patients (20 families) with SSADH deficiency (4- hydroxybutyric acid-uria) are presented. The age at diagnosis ranged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families. Outcome Measurements. The following abnormalities were observed (frequency in 23 patients): motor delay, including fine-motor skills, 78%; language delay, 78%; hypotonia, 74%; mental delay, 74%; seizures, 48%; decreased or absent reflexes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; neonatal problems, 26%; and electroencephalographic abnormalities, 26%. Associated findings included psychoses, cranial magnetic resonance or computed tomographic abnormalities, and ocular problems in 22% or less of patients. Therapy with vigabatrin proved beneficial to varying degrees in 35% of the patients. Normal early development was noted in 30% of patients. Conclusions. Our data imply that two groups of patients with SSADH deficiency exist, differentiated by the course of early development. Our recommendation would be that accurate, quantitative organic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, motor, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis can be confirmed by determination of enzyme activity in white cells from whole blood. We think that increased use of organic acid determination will lead to increased diagnosis of SSADH deficiency and a more accurate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metabolic and clinical profiles of SSADH deficiency.

AB - Objectives. To further define the clinical spectrum of the disease for pediatric and metabolic specialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde dehydrogenase (SSADH) deficiency in the differential diagnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative organic acid analysis in such patients. Patients. The clinical features of 23 patients (20 families) with SSADH deficiency (4- hydroxybutyric acid-uria) are presented. The age at diagnosis ranged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families. Outcome Measurements. The following abnormalities were observed (frequency in 23 patients): motor delay, including fine-motor skills, 78%; language delay, 78%; hypotonia, 74%; mental delay, 74%; seizures, 48%; decreased or absent reflexes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; neonatal problems, 26%; and electroencephalographic abnormalities, 26%. Associated findings included psychoses, cranial magnetic resonance or computed tomographic abnormalities, and ocular problems in 22% or less of patients. Therapy with vigabatrin proved beneficial to varying degrees in 35% of the patients. Normal early development was noted in 30% of patients. Conclusions. Our data imply that two groups of patients with SSADH deficiency exist, differentiated by the course of early development. Our recommendation would be that accurate, quantitative organic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, motor, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis can be confirmed by determination of enzyme activity in white cells from whole blood. We think that increased use of organic acid determination will lead to increased diagnosis of SSADH deficiency and a more accurate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metabolic and clinical profiles of SSADH deficiency.

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