27683825 Visualization

The proband is a 19 Age - year Age - old Age woman Sex , first Family_history child Family_history of Family_history healthy Family_history unrelated Family_history parents Family_history .
Her family Family_history history Family_history was Family_history unremarkable Family_history .
She was born History at History term History after History a History normal History pregnancy History .
The perinatal Diagnostic_procedure period Diagnostic_procedure was uneventful Lab_value and her early Diagnostic_procedure development Diagnostic_procedure was referred to as normal Lab_value , but after 1 Date   year Date of Date age Date , psychomotor Disease_disorder delay Disease_disorder became evident Severity .
She started walking Activity autonomously Detailed_description at 22 Date   months Date , with poor Lab_value balance Diagnostic_procedure and frequent Frequency falls Sign_symptom .
At 3 Date   years Date of Date age Date , she developed a demyelinating Disease_disorder sensorimotor Disease_disorder neuropathy Disease_disorder and a brain Biological_structure MRI Diagnostic_procedure disclosed supratentorial Biological_structure leukodystrophy Disease_disorder .
During her childhood, the clinical Diagnostic_procedure signs Diagnostic_procedure remained stable Lab_value .
At 10 Date   years Date , her walking Disease_disorder difficulties Disease_disorder worsened Lab_value , and limb Biological_structure weakness Sign_symptom and tremor Sign_symptom ensued.
The neurological Diagnostic_procedure evaluation Diagnostic_procedure showed dysarthria Sign_symptom , dysmetria Sign_symptom , ataxic Lab_value gait Diagnostic_procedure and hyporeflexia Sign_symptom in the four Biological_structure limbs Biological_structure with muscle Disease_disorder wasting Disease_disorder .
She was able to walk Activity alone Detailed_description only Lab_value for Lab_value a Lab_value few Lab_value steps Lab_value with an ataxic Lab_value gait Diagnostic_procedure .
Mild Severity cognitive Disease_disorder impairment Disease_disorder was documented ( IQ Diagnostic_procedure 75 Lab_value , WISC Detailed_description - R Detailed_description scale Detailed_description ).
Histological Diagnostic_procedure analysis Diagnostic_procedure of a muscle Biological_structure biopsy Diagnostic_procedure showed hypo/atrophy Sign_symptom of fibres Biological_structure .
The clinical Diagnostic_procedure evolution Diagnostic_procedure was slowly Lab_value progressive Lab_value .
At her last follow Clinical_event - up Clinical_event examination, at 19 Date   years Date of Date age Date , she was able to walk Activity alone Detailed_description only with ankle Detailed_description - foot Detailed_description orthotic Therapeutic_procedure aids Therapeutic_procedure and had developed a marked Severity dorsal Biological_structure - lumbar Biological_structure scoliosis Disease_disorder .
Other clinical Diagnostic_procedure signs Diagnostic_procedure were stable Lab_value .
Neurophysiological Diagnostic_procedure studies Diagnostic_procedure confirmed worsening Lab_value of her mixed Detailed_description axonal Biological_structure demyelinating Disease_disorder peripheral Disease_disorder neuropathy Disease_disorder .
Brain Biological_structure and spinal Biological_structure cord Biological_structure MRI Diagnostic_procedure showed mild Severity extension Lab_value of signal Sign_symptom abnormalities Sign_symptom and extensive Severity cavitations Sign_symptom in the cerebral Biological_structure white Biological_structure matter Biological_structure ; the cerebellum Biological_structure and brainstem Biological_structure were spared Sign_symptom but the spinal Biological_structure cord Biological_structure was thin Sign_symptom with no obvious focal Detailed_description lesions Sign_symptom (figure 1A).
Plasma Diagnostic_procedure lactate Diagnostic_procedure was 2.9 Lab_value   mM Lab_value (n.v. <2.1).