Progressive Cerebellar Syndrome

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A 35 year old man with progressive cerebellar syndrome and abnormal eye movementsHistoryUnclear history of childhood cognitive problems requiring special education framework within normal schoolAge 15 developed generalised seizures and myoclonusAbove well controlled with sodium valproateHistory 2In early 20’s began suffering from action tremor, slurred speech, instability walking and decreased co-ordination in armsIn 1993 (aged 23) hospitalised electively without reaching diagnosisOver last few years epilepsy remains well controlledProblems with walking co-ordination worsening, over lat few years confined to wheelchairHistory IIIFH of epilepsyNo FH of cerebellar diseaseNo consanguinityHistory IVDrug history:-Depalept solution 1200mg /dMysoline 05mg/dClonazepam liquidVitamin A + DFolic AcidRivotrilExaminationBilateral exophthalmusSevere dysarthriaPEARLANo KFR’sFundi normalEOM: - Pursuit movements in tact - Very slow / absent saccades - No nuclear / infranuclear problemExamination IITone mildly reducedPower preservedDecreased reflexes symmetricallyNo pyramidal signsSensation preservedDysmetria, DDK, int. tremor bilaterallyUnable to standAthetotic / dystonic movements mainly in armsClinical summaryProgressive cerebellar syndromeEpilepsy ? Red herring (strong FH)Myoclonus (controlled)Slowed / absent saccades (supranuclear problem)

Investigations to dateHaematology:-FBCINRBlood smear

BiochemistryElectrolytesLiver & Renal functionCholesterolAlbuminLactateAmmoniaCeruloplasminCopperThyroid functionBiochemistry IIUrinary organic acidsUrinary amino acidsHexosaminidaseAryl sulphataseGalacto cerebrosidaseImmunoglobins

VitaminsE

B1B6B12

MicrobiologyVDRLRubella antibodies

CSFNormal protein (348 mg/l)No cellsHistopathologySkin biopsy Rectal biopsy Muscle biopsyElectrophysiologyNCV:Mild slowing of sensory potentialsNormal motor potentialsEEGIncreased Beta activityNo slow or epileptic activityNo asymmetryImagingAbdominal USSMRI + MRS:General atrophy (more pronounced in cerebellum)Increased choline and AA signal posteriorlyNo increased lactate signalGeneticsSCA batterySCA 1SCA 2SCA 3SCA 6SCA 7DRPLAFriedrich AtaxiaLysosomal enzymesInvestigations pendingCholestanolAFPGSS codon

Progressive myoclonic epilepsyUsually inborn errors of metabolismMyoclonusEpilepsyCognitive declineProgressiveLafora body diseaseUnverricht-Lundborg diseaseLysosomal disorders (e.g. NPD, NCL)Mitochondrial disorders (MERRF and others)

Inherited ataxias with known metabolic defectWilsonCTXRefsumGM2 gangliosidosisAVEDPureHARPBassen-KornzweigLysosomal Niemann-Pick C AR – rare Cognitive decline , Ataxia , Movements , Myoclonus , Seizures , Vertical suparanuclear gaze palsy , PsychosisDiagnosis: Bone Marrow ; Fibroblasts with lowered cholesterol esterification rate 18q11-q12

SummaryAlmost certainly “ early onset genetic ataxia”Probably AR inheritencePhenotype is “AOA”May have AOA1 or AOA 2 mutation