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Article

Mixed movement disorders re vealing an atypical form of creatine deficiency syndrome

Nasrallah Fahmi, OMAR Souheil, KAABACHI Naziha, 2014

Iranian Journal of Neurology, 14, 1, 47-49, Décembre 2014

Résumé

Creatine deficiency syndromes (CDS) are inborn errors
of creatine (Cr) biosynthesis characterized by mental
retardation and severe language impairment.1
Movement disorders, mainly dystonia have been
described as additional features in CDS.2 We report on
an exceptional case of mixed movement disorders due
to an atypical form of CDS. A.H. is a 26-year-old man,
born to second-degree consanguineous parents with
family history of mental retardation in maternal cousin.
Pregnancy and delivery were normal. Psychomotor
development was normal. At the age of 6 years, he
presented with a progressive cervical and left-hand
abnormal posture with myoclonic jerks. When first
examined at the age of 20, he had myoclonic jerks in the
left upper limb with cervical and left hand dystonia.
The diagnosis of heredodegenerative disease (inborn
errors of metabolism) was evoked because of the
consanguinity, family history, age of onset and mixed
movement disorders. Oriented biological and imaging
investigations were performed. Brain magnetic
resonance imaging was normal. Serum copper level
was 90 (Normal range: 80-160); urine copper level was
14 (Normal range < 20 μg/24 h); ceruloplasmin level
was 0.260 (normal level: 0.2-0.6 g/l). Genetic testing for
DYT1 gene was negative. Peripheral blood smear was
normal. Amino acids and organic acids abnormalities
and remethylation disorders were excluded. Urinary Cr
and guanidinoacetate (GAA) were analyzed by gas
chromatography–mass spectrometry; they showed low
level of Cr associated with a relatively high GAA
concentration and low Cr/GAA ratio (0.45) whereas a
normal value exceeds 1.3 The diagnosis of mixed
movement disorders due to an atypical form of CDS
was made after the determination of intermediate GAA
methyltransferase (GAMT) activity in lymphoblasts.
Measurement of GAMT activity in lymphoblasts was
performed according to Verhoeven et al.4
The clinical picture associated with the abnormal
levels of Cr and GAA call the attention to CDS and
particularly GAMT deficit for this patient. GAMT is
the second enzyme in the process of Cr synthesis
resulting from converting guanidinoacetate and Sadenosylmethionine
into Cr and Sadenosylhomocysteine.
Patients with GAMT
deficiency exhibit complex clinical phenotypes with
hyperkinetic movement disorders such as generalized
dystonia and severe mental retardation with
epilepsy.1 Though reduced the GAMT activity in this
patient, which was 0.107 nmol/h/mg protein (normal
values: 0.29-0.31 nmol/h/mg protein), is equivalent to
that reported for heterozygous parents.5 As shown in
figure 1, the GAMT activity of this patient was
intermediate between that of the control subject and
patients with a total GAMT deficiency, it was below
the detection limit in GAMT deficiency patient
(< 0.01 nmol/h/mg protein). Two hypotheses could
be proposed to explain the association of a low
Cr/GAA ratio with a partial deficit of GAMT activity
and a clinical picture characterized by the presence of
mixed movement disorders. The low Cr/GAA ratio
could be attributed to a high endogenous
consumption of Cr originating partly physiologically
(50%) from high meat nutrition and partly (50%) from
body synthesis. As for the partly deficient GAMT
activity, it could be an atypical form of CDS with a
non-ubiquitous GAMT deficiency. Additional
explanations and hypothesis would be advanced once
similar cases are studied.