Dopamine-agonist responsive Parkinsonism in a patient with the SANDO syndrome caused by POLG mutation
© Bandettini di Poggio et al.; licensee BioMed Central Ltd. 2013
Received: 5 March 2013
Accepted: 25 September 2013
Published: 7 October 2013
Disorders of oxidative phosphorylation affects 1/5000 individuals and present heterogeneous involvement of tissues highly dependent upon ATP production.
Here we present the case of a 48-year-old woman carrying a homozygous mutation (p.A899T) in mitochondrial polymerase gamma (POLG) and manifesting with a complex neurological phenotype including Dopamine-agonist responsive Parkinsonism.
This case report is further evidence that mitochondrial dysfunction might play a role in Parkinson’s Disease pathogenesis and helps in identification of apparent mutation-specific clinical characteristics. Mutations in POLG should be looked for in cases of Parkinsonism, especially when multisystem neurological involvement is found.
KeywordsPOLG Parkinsonism Mitochondrial dysfunction Ataxia Progressive external ophthalmoparesis
The mitochondrial polymerase gamma (POLG) represents a major human disease gene and may account for up to 25% of all mitochondrial diseases, at least in UK and in Italy . Among the possible clinical presentations, Alpers-Huttenlocher syndrome (AHS) in children and inherited progressive external ophthalmoparesis (PEO) in adults — either as the sole manifestation or in association with additional neurological features [2, 3] — are the most common. Movement disorders are possible manifestations in AHS and have occasionally been described in adult PEO .
Here we report on a patient carrying a homozygous mutation in POLG and manifesting with a complex neurological phenotype fitting the clinical diagnosis of SANDO (sensory ataxic neuropathy, dysarthria, and cophthalmoparesis) syndrome including Dopamine-agonist responsive Parkinsonism.
The 82-year-old mother and two of the four living sisters, aged 57 and 45 years, had a normal neurological examination. The father of the proposita had died at the age of 72 because of myocardial infarction but he was referred to be free of neurological complaints.
The present report offers two main considerations. The patient we described combines the clinical features of SANDO syndrome complicated with late-onset Parkinsonism and mood disorder. In previous years, co-existence of Parkinsonism and POLG mutations has been described, suggesting that mitochondrial dysfunction might play a role in the pathogenesis of PD . Our case report is further evidence that abnormal oxidative metabolism and loss of mtDNA integrity might be implicated in similar conditions. Whilst is evident that POLG does not represent a frequent etiology in PD-like syndromes, it seems not too speculative to hypothesize that alterations in mtDNA fidelity and subsequent impaired protein synthesis likely compromise mitochondrial bioenergetics, dynamics, transport, or their combination, in dopaminergic neurons . Similar to other cases of “mitochondrial parkinsonisms”, our patient had benefit with antiparkinson drugs, underling the importance of a correct diagnosis [4, 9–12].
A further consideration emerges from the evidence of an additional association between the POLG p.A899T variant and SANDO syndrome. The p.A899T has initially been described in compound heterozygosity [13, 14] and frequently associated with the clinical triad of sensory ataxic, ptosis, and PEO together with a mood disorder and a movement disorder such as Dopamine-agonist responsive parkinsonism. In the face of an ever increasing, pleiomorphic array of features associated with mutations in POLG, identification of apparent mutation-specific clinical characteristics might facilitate molecular confirmation in complex patients, prevent possible co-morbidities, and permit to adopt effective symptomatic therapies.
Mitochondrial polymerase gamma
Progressive external ophthalmoparesis
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
Mini Mental State Examination
Unified Parkinson’s Disease Rating Scale.
We wish to thank the patient, who gave written consent for publication, and her family.
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