Report of two never treated adult sisters with aromatic L-amino Acid decarboxylase deficiency: a portrait of the natural history of the disease or an expanding phenotype?
Two sisters were diagnosed in their adulthood with aromatic L-amino acid decarboxylase (AADC) deficiency (OMIM#608643). They experienced early myasthenia-like manifestations, myoclonic jerks, oculogyric crises, tremors, and developmental delay during childhood; clinical stabilization afterwards; and spontaneous improvement during adolescence and young adulthood. Two novel pathogenic mutations on DDC gene [p.Tyr37Thrfs*5 (c.105delC) and p.F237S (c.710 T>C)] were associated with undetectable enzyme activity in plasma and only a mild reduction of biogenic amines in cerebrospinal fluid (CSF). The increase of both 3-O-methyldopa and 5-hydroxytryptophan on CSF was the most relevant biochemical alteration denoting AADC defect in these subjects. Transdermal rotigotine remarkably improved their gross motor functions and the asthenic status they complained. The present cases broaden the phenotypic spectrum of AADC deficiency and suggest that (1) AADC defect is not a progressive neurological disease and behaves rather as a neurodevelopmental disorder that improves during the second decade of life; (2) treatment-naïve adults can still respond well to neurotransmitter therapy; and (3) the possibility of a mild presentation of AADC deficiency should be considered when examining young adults with asthenic and parkinsonian symptoms.
Division of Child Neurology, Department of Pediatrics and Child Neurology and Psychiatry, "Sapienza", University of Rome, Via dei Sabelli, 108-00141, Rome, Italy, vincenzo.leuzzi@uniroma1.it.
Vincenzo
V
Leuzzi
Mario
M
Mastrangelo
Agata
A
Polizzi
Cristiana
C
Artiola
André B P
AB
van Kuilenburg
Carla
C
Carducci
Martino
M
Ruggieri
Rita
R
Barone
Barbara
B
Tavazzi
Nico G G M
NG
Abeling
Lida
L
Zoetekouw
Vito
V
Sofia
Mario
M
Zappia
Claudia
C
Carducci