Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood.

Samuel Lapalme-Remis, Evan Cole Lewis, Christine De Meulemeester, Pranesh Chakraborty, K Michael Gibson, Carlos Torres, Alan Guberman, Gajja S Salomons, Cornelis Jakobs, Andre Ali-Ridha, Mahsa Parviz, Phillip L Pearl

Journal: Neurology 2015;85(10):861-5

PMID: 26268900

Free Full Text on PubMed Central View on PubMed

Abstract

OBJECTIVE

The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life.

METHODS

A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following hospitalization for progressive decline, escalating seizures, and prolonged periods of altered consciousness. We present a detailed review of his clinical course and reviewed our SSADH deficiency database adult cohort to derive natural history information.

RESULTS

Of 95 patients in the database for whom age at diagnosis is recorded, there are 40 individuals currently aged 18 years or older. Only 3 patients were diagnosed after age 18 years. Of 25 adults for whom data are available after age 18, 60% have a history of epilepsy. Predominant seizure types are generalized tonic-clonic, absence, and myoclonic. EEGs showed background slowing or generalized epileptiform discharges in two-thirds of adults for whom EEG data were collected. History of psychiatric symptoms was prominent, with frequent anxiety, sleep disturbances, and obsessive-compulsive disorder.

CONCLUSIONS

We identified patients older than 18 years with SSADH deficiency in our database following identification and review of a patient diagnosed in the seventh decade of life. The illness had a progressive course with escalating seizures in the index case, with fatality at age 63. Diagnosis in adulthood is rare. Epilepsy is more common in the adult than the pediatric SSADH deficiency cohort; neuropsychiatric morbidity remains prominent.

Address: From the Division of Neurology, Department of Medicine (S.L.-R., C.D.M., A.G.) and Department of Radiology (C.T.), The Ottawa Hospital, University of Ottawa, Ontario, Canada; Division of Neurology (E.C.L.) and Department of Pediatrics (P.C.), Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada; Division of Experimental and Systems Pharmacology (K.M.G.), Washington State University College of Pharmacy, Spokane, WA; Department of Clinical Chemistry (G.S.S., C.J.), Metabolic Unit, Polikliniek rec. K (PK 1X 009), VU University Medical Center, Amsterdam, the Netherlands; University of Ottawa Eye Institute (A.A.-R.), Ottawa, Ontario, Canada; and Department of Epilepsy & Clinical Neurophysiology (M.P., P.L.P.), Harvard Medical School, Boston Children's Hospital, Boston, MA. Dr. Lapalme-Remis is currently with the Mayo Clinic, Rochester, MN. Dr. Lewis is currently with The Hospital for Sick Children, Toronto, Ontario, Canada. Dr. Ali-Ridha is currently with McGill University, Montreal, Quebec, Canada. [email protected].; From the Division of Neurology, Department of Medicine (S.L.-R., C.D.M., A.G.) and Department of Radiology (C.T.), The Ottawa Hospital, University of Ottawa, Ontario, Canada; Division of Neurology (E.C.L.) and Department of Pediatrics (P.C.), Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada; Division of Experimental and Systems Pharmacology (K.M.G.), Washington State University College of Pharmacy, Spokane, WA; Department of Clinical Chemistry (G.S.S., C.J.), Metabolic Unit, Polikliniek rec. K (PK 1X 009), VU University Medical Center, Amsterdam, the Netherlands; University of Ottawa Eye Institute (A.A.-R.), Ottawa, Ontario, Canada; and Department of Epilepsy & Clinical Neurophysiology (M.P., P.L.P.), Harvard Medical School, Boston Children's Hospital, Boston, MA. Dr. Lapalme-Remis is currently with the Mayo Clinic, Rochester, MN. Dr. Lewis is currently with The Hospital for Sick Children, Toronto, Ontario, Canada. Dr. Ali-Ridha is currently with McGill University, Montreal, Quebec, Canada.

DOI: 10.1212/WNL.0000000000001906

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/aminoacidmetabolismdisorde...

Subscription / membership required

Full Text Sources:

MeSH Terms: Adolescent, Adult, Amino Acid Metabolism, Inborn Errors, Cross-Sectional Studies, Databases, Factual, Developmental Disabilities, Fatal Outcome, Female, Humans, Male, Middle Aged, Succinate-Semialdehyde Dehydrogenase, Young Adult