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Reykjavík 12.12. 2008
Patient clinical summary
Ella Dís Laurens is a three year old girl with aprox. 1.5 year history of progressive symmetrical muscular weakness involving both upper and lower extremities. Her weakness was initially more marked in the upper compared to the lower extremities and still is, but in both upper and lower extremities she is more affected distally than proximally. Since her diagnosis at approx 18 months of age she has progressively lost most of her motor function, more so in the upper extremities, trunk and paraspinal muscles, and over the last 6 months has shown increase in bulbar involvement. Recently we have seen progressive pendular nystagmus and evidence for optic nerve atrophy. Clinically she has never had any sensory or cerebellar symptoms and her intellectual ability has been normal.
Her initially work-up consisted of a normal MRI of the brain and spinal cord, and a second MRI in June 2008 was also normal. Initially she had a normal spinal fluid examination and a normal biochemical work-up including CBC, CK, lactate, bicarbonate and transaminases. All these parameters have repeatedly been normal and a new spinal fluid examination in June 2008 was also normal. Five weeks ago, in early November she developed a normochromic normocytic anemia with low retic count, and normal white cell and platelet counts. This has been interpreted as a case of TEC unrelated to her underlying disease.
Comprehensive biochemical and genetic work-up, including amino and organic acids, phytanic acid, lysosomal enzymes, and CSF and peripheral lactate and pyruvate has all been normal. In June, a low level of cytochrome oxidase prompted a more comprehensive workup for a possible mitochondrial abnormality was started, but so far no abnormalities have been detected. Genetic tests have confirmed that SMN1 gene copy number is 2 and no deletions were detected. SMARD1 mutation testing (IGHMBP2 gene) showed normal results. A genetic panel looking for evidence for HMSN has been normal and gene test for FSH- muscular dystrophy has been normal.
Electrophysiologic studies initially showed the denervation pattern in all muscles tested, both proximally and distally but normal nerve conduction velocities in both motor and sensory nerves. A repeat study done at another institution reportedly showed mildly delayed conduction velocities involving both motor and sensory nerves, and the denervation patterns in all muscles sampled as before.
A muscle biopsy from a thigh muscle at presentation did not show any abnormalities and a later biopsy of the deltoid muscle was consistent with neurogenic atrophy. A sural nerve biopsy showed both axonal and demyelinating features, interpreted as consistent with a primarily axonal and secondary demyelinating disorder. No evidence for an inflammatory process was found.
Since her initial presentation Ella's course has been progressive. She seemed to lose muscle strength in her upper body much more quickly than her lower body, and at present she has essentially no movement of her arms but she is able to kick and use her thigh muscles to some extent. Progressive bulbar involvement including tongue atrophy and facial weakness has been evident.
Ella was maintained initially on a non-invasive BPAP ventilation at night but because of progressive respiratory insufficiency but for several months she has needed continuous non-invasive respiratory support with cough-assist.
In summary:
Ella Dís has a very rapidly progressive neuromuscular disease that from the evidence available seems to be a axonal degenerative motor neuron disease that does not have typical features of SMA, and genetic testing do not support that diagnosis. SMARD and HMSN gene testing have been negative.
For a time Ella was treated with immunoglobulins and steroids with the idea in mind that possibly she had a chronic inflammatory poly-neuropathy but there was no response to those efforts.
There is no family history of neuromuscular disease, and past medical history is also normal.
For now Ella Dís is in the Childrens Hospital at Landspítali in Reykjavík on a continuous BEPAP- ventilation. She is breathing room air.
If further information is needed, please contact me.