Neurocognitive profiles in MSUD school-age patients.
Maple syrup urine disease (MSUD), an inborn error of amino acids catabolism is characterized by accumulation of branched chain amino acids (BCAAs) leucine, isoleucine, valine and their corresponding alpha-ketoacids. Impact on the cognitive development has been reported historically, with developmental delays of varying degree. Currently, earlier diagnosis and improved management allow a better neurodevelopment, without requirement of special education. However, specific impairments can be observed, and so far, results of detailed neurocognitive assessments are not available. The aim of this study was to analyse neurocognitive profiles of French MSUD patients. This was a multicentre retrospective study on MSUD patients who underwent neurocognitive evaluation at primary school age. Twenty-one patients with classical neonatal onset MSUD were included. The patients' mean age at the time of evaluation was 8.7 years. The mean intellectual quotient (IQ) score was in the normal range (95.1 ± 12.6). In a subset of eight patients, a consistent developmental pattern of higher verbal than performance IQ was observed (mean of the difference 25.7 ± 8.7, p < 0.0001). No correlation could be established between this pattern and long-term metabolic balance (BCAA blood levels), or severity of acute metabolic imbalances, or leucine blood levels at diagnosis and time to toxin removal procedure. These data show that some MSUD patients may exhibit an abnormal neurocognitive profile with higher verbal than performance abilities. This might suggest an executive dysfunction disorder that would need to be further investigated by specialized testing. This pattern is important to detect in MSUD, as appropriate neuropsychological treatment strategies should be proposed.
Reference Centre for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, 48 boulevard Sérurier, 75019, Paris, France.
Juliette
J
Bouchereau
Reference Centre for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, 48 boulevard Sérurier, 75019, Paris, France.
Julie
J
Leduc-Leballeur
Reference Centre for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, 48 boulevard Sérurier, 75019, Paris, France.
Samia
S
Pichard
Biochemistry Department, Robert Debré University Hospital, APHP, Paris, France.|Robert Debré University Hospital, PROTECT, INSERM U1141, University Paris Diderot, Sorbonne Paris Cité, Paris, France.
Apolline
A
Imbard
Biochemistry Department, Robert Debré University Hospital, APHP, Paris, France.|Robert Debré University Hospital, PROTECT, INSERM U1141, University Paris Diderot, Sorbonne Paris Cité, Paris, France.
Jean-François
JF
Benoist
Reference Centre for Inborn Errors of Metabolism, Necker University Hospital, APHP, Paris, France.
Marie-Thérèse
MT
Abi Warde
Reference Centre for Inborn Errors of Metabolism, Necker University Hospital, APHP, Paris, France.
Jean-Baptiste
JB
Arnoux
Reference Centre for Inborn Errors of Metabolism, Necker University Hospital, APHP, Paris, France.
Valérie
V
Barbier
Reference Centre for Inborn Errors of Metabolism, Necker University Hospital, APHP, Paris, France.
Anaïs
A
Brassier
Metabolic Disease Department, Children University Hospital, Toulouse, France.
Pierre
P
Broué
Reference Centre for Inborn Errors of Metabolism, La Timone University Hospital, APHM, Marseille, France.
Aline
A
Cano
Reference Centre for Inborn Errors of Metabolism, La Timone University Hospital, APHM, Marseille, France.
Brigitte
B
Chabrol
Pediatrics Department, Hôpital Nord, Saint-Etienne University Hospital, Saint-Etienne, France.
Gilles
G
Damon
Pediatrics Department, Hôpital Nord, Saint-Etienne University Hospital, Saint-Etienne, France.
Claire
C
Gay
SESSAD Arc en ciel, Le Barp, France.
Isabelle
I
Guillain
Biochemistry Department, Necker University Hospital, APHP, Paris, France.|INSERM UMR-S 1124, University Paris Descartes, Paris, France.
Florence
F
Habarou
Pediatrics Department, Bordeaux University Pellegrin Hospital, Bordeaux, France.
Delphine
D
Lamireau
Biochemistry Department, Necker University Hospital, APHP, Paris, France.|INSERM UMR-S 1124, University Paris Descartes, Paris, France.
Chris
C
Ottolenghi
Reference Centre for Inborn Errors of Metabolism, La Timone University Hospital, APHM, Marseille, France.
Laetitia
L
Paermentier
Biochemistry Department, Institut Fédératif de Biologie, Purpan University Hospital, Toulouse, France.|INSERM UMR1037, Toulouse III University, Toulouse, France.
Frédérique
F
Sabourdy
Metabolic Disease Department, Children University Hospital, Toulouse, France.
Guy
G
Touati
Reference Centre for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, 48 boulevard Sérurier, 75019, Paris, France.
Hélène
H
Ogier de Baulny
Reference Centre for Inborn Errors of Metabolism, Necker University Hospital, APHP, Paris, France.|INSERM UMR-S 1124, University Paris Descartes, Paris, France.
Pascale
P
de Lonlay
Reference Centre for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, 48 boulevard Sérurier, 75019, Paris, France. manuel.schiff@aphp.fr.|Robert Debré University Hospital, PROTECT, INSERM U1141, University Paris Diderot, Sorbonne Paris Cité, Paris, France. manuel.schiff@aphp.fr.
Manuel
M
Schiff
D000597:Amino Acids, Branched-Chain / Q000097:blood; D002648:Child; D003071:Cognition / Q000502:physiology*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007532:Isoleucine / Q000097:blood; D007930:Leucine / Q000097:blood; D008297:Male; D008375:Maple Syrup Urine Disease / Q000097:blood / Q000503:physiopathology*; D012189:Retrospective Studies; D012574:Schools; D014633:Valine / Q000097:blood
D000597:Amino Acids, Branched-Chain; D007532:Isoleucine; D007930:Leucine; D014633:Valine