Type 3 / GD3 (continued), CNS Sx in GD3, Parameters / GD 1 Summary

Type 3 (continued)

(Abdelwahab, 2017 #548)= Egyptian study,(n=78) mean age 7.9 y] Supranuclear palsy of horizontal gaze (97.1%),, and of both horizontal and vertical gaze (50%), bulbar symptoms (55.9%),, seizures (29.4%), convergent strabismus (29.4%),, abnormal gait (20.6%) and neck retroflexion (4.4%),.

IQ: 71.1 (Borderline)

29% SZ, 12% no sz but EEG abnormality, (합치면 EEG이상은 40%), 59% no sz no EEG abnormality. with this blue part, I can’t find reference.

(Abdelwahab, 2016 #803)

(Lee, 2012 #827) korean nGD patients (n=7), onset of CNS Sx 8.7y, epilepsy 57%, eye 42.8%, tremor 28.6%, cognition 28.6%

Type 3 + PD

• 2004 Wong에 이 환자군은 없음.

‘gaucher cell: : (Gözdaşoğlu, 2015 #829) tubules (accumulated cerebroside) are seen by EM, (GlcSph is not directly seen to be accumulated!)

CNS Sx in GD3

(Davies, 2011 #552)

All patients were receiving ERT.) Fig3 is important. Each domain 의 prevalence와 longitudinal change over 4 y 보여줌. Cerebellar signs & ataxia가 흔하면서 change.

Davies 2011 chart title: Percentage of patients presenting according to each SST domain at Baseline and Follow Up. Bar-chart legend: Baseline, Follow Up. mSST domain labels (in chart order): HGP, Spinal Alignement, Cerebellar Signs, Cognitive Ability, Ataxia/Gait, Pyramidal, Ophthamology, Speech, Extrapyramidal, Epilepsy, Swallowing.

(Tylki-Szymanska, 2010 #553)

N=39, HGP: Horizontal gaze palsy, Mean interval for follow up: 3.0 y, Duration: 4.0-11y

Each domain 의 prevalence와 onset age 보여줌.

Tylki-Szymanska 2010 chart axes: Percent of Patients (top, 0-100, grey bars), Median Age First Noted (bottom, 0-10, red dots). Row labels in chart order:

• Stridor
• Swallowing difficulties
• Pincer grasp
• Muscle weakness
• Walking ability
• Chewing difficulties
• Slow object tracking
• Head movement rather than eye movement
• Convergent squint
• Ability to look to the extreme up or down
• Ability to look to the extreme right or left
• Head thrusting
• Wide base gait
• Retroflexion of the head
• Myoclonus
• Extrapyramidal features
• Spasticity
• Dysarthria
• Rapid finger tapping
• Seizures
• Extensor plantar response
• Tremor when reaching
• Tremor at rest

Myoclonus & myoclonic sz	The myoclonus and myoclonic seizures observed in nGD are thought to be caused by cortical neuronal hyperexcitability
EEG	(medscape 2020) posterior spikes and sharp waves, diffuse spike and waves, and photomyoclonic and photoparoxysmal responses may be present
Ataxia

Parameters / GD 1 Summary

	GlcCer plasma	GlcSph plasma	Chitotriosidase plasma	Spleen volume	Liver volume	Hemoglobin (g/L)	Platelet	Bone	Serum CCL18 (ng/ml) (pulmonary and activation-regulated chemokines)	Gaucher disease severity score index-type1 (GauSSI-1).44
Pathophysiology		(2016Smid) Toxic and directly implicate in GD pathology (hemolysis ↓ PKC 등)	(2016 Smid) not pathogenic but a mere reflection of activated macrophages, it					Macrophagee in bone marrow
Evidence								거의 all bone problem, 62% radiologic bone disease, 43% bone pain
Method				imaging	imaging			2015 Marcos. Bone Marrow Burden Score (BMB); Severity Score Index (SSI); DS3; Herman Score; standard		GauSSI-1: six domains, ie, skeletal, hematological, biomarker, visceral, lung, and neurological, a total score of 42 points. A higher score indicates more severe GD.
Normal				2.0% body weight	2.5% body weight
Severity multiple of normal	•	•	•	<2×MN = 1, 2-5×MN = 2, 5 - 15×MN = 3, > 15×MN = 4 splenectomy = 5.	<1.25×(MN) = 1, 1.25 - 1.5×MN = 2, 1.5 - 2.5×MN= 3 > 2.5×MN = 4.
ERT response	20x → 2x (Treatment duration not mentioned, but this level is viewed as being similar to normal range and reported by many others)	2016 Murugesan 59x → 13.5 (after 3.6 y) lyso-GL1 levels decrease to half their initial value within 1 year of ERT although individual patient trends are heterogeneous. Subsequently, with ongoing ERT, lyso-GL1 levels appear to plateau by 3-4 years with a mean average residual	-2016 Murugesan ↑ 29.2 x - In 2y: half reduction, (macrophage activation을 경유하므로 시간 더 드는듯?) In 4y: 2-fold upper limit of normal	17.2 → 6.1 (after 3.6 y)	1.8 → 1.3 (after 3.6 y)	12.3 → 13.6 (after 3.6 y)	158.7 → 201.4 (after 3.6 y)	다소 refractory: 40% refractory after 18m of ERT, 특히 osteonecrosis등은 irreversible	7.2 → 7.5(after 3.6 y) 2.6 → 2.8(after 3.6 y) 3.6→ 3.6 (after 3.6 y)	- 603.02 → 276.7(after 3.6 y) 2016 Murugesan - 2016 Smid decreased but not normalized completely after 2 year Tx

Uncertain Spans

location	transcription	uncertainty
GD 1 Summary / GlcSph ERT cell	lyso-GL1 levels appear to plateau by 3-4 years with a mean average residual	the sentence ends mid-clause with residual; the rest is clipped at the cell’s right edge.
GD 1 Summary / GauSSI ERT cell	- 603.02 → 276.7(after 3.6 y) 2016 Murugesan	reads as written; the leading dash precedes a fragmentary number that could begin with a 60 or 603.02.