Table 1.

Patients’ characteristics.

Patient no.	Age of onset/age of diagnosis (years)	First symptom observed, age (years)	Medication	Genotype	Neurologic and psychiatric findings	Systemic manifestation and other findings	MRI findings	Ophthalmologic and clinical oculomotor findings	IQ
PATIENTS FOLLOWED UP LONGITUDINALLY
1	1/1	Oculomotor disturbance (not specified), 19	Imiglucerase 3,200 U/2 weeks, eliglustat 100 mg/day, spironolactone 150 mg/day, calcium 1,500 mg/day, potassium 7,200 mg/day, magnesium 450 mg/day, vitamin D 3,000 U/day, pantoprazole 40 mg/day	GBA: W5333X S384F + R535C	Hyperreflexibility, pyramidal signs, clonus, stance and gait ataxia, dystonia	Fixed kyphosis	N	Alternating convergent squint operatively corrected, bilaterally, persisting esotropia R, visual acuity 0.5 R, 1.0 L, horizontal saccade paresis, slow vertical saccades down > up, impaired horizontal > vertical OKN, bilaterally impaired VOR	79
2	0/0	Retarded motor development, Oculomotor disturbance (not specified), 16	Imiglucerase 2,000 U/2 weeks	GBA: L444P L444P	Discrete stance and gait ataxia, dysmetria, hyperreflexibility, cognitive impairment	Hepatosplenomegaly, chronic obstructive lung disease	NP	Alternating convergent squint, visual acuity 0.8 R, 0.8 L, abducens palsy bilaterally, slow saccades horizontal > vertical, smooth pursuit impaired vertical > horizontal, horizontal impaired OKN, impaired VOR bilaterally	68
3a	1/1	Oculomotor disturbance (not specified), 2	Imiglucerase 1,600 U/2 weeks	GBA: L444P L444P	Dystonia	Discrete hepatomegaly, chronic obstructive lung disease, bronchial asthma, atopic dermatitis, lactose intolerance	N	Slow horizontal saccades, impaired horizontal OKN, discrete impaired VOR	101
4a	1/1	Oculomotor disturbance (not specified), 2	Imiglucerase 2,000 U/2 weeks	GBA: L444P L444P	Hyperreflexibility, hypotonus of lower extremities	Chronic obstructive lung disease, discrete thoracic kyphosis, hepatomegaly, neurodermatitis	N	Visual acuity 1.0 R, 1.0 L, slow horizontal saccades with curved trajectory (“around the house sign”), impaired horizontal OKN, discrete impaired VOR	105
5b	1/1	Oculomotor disturbance (not specified), 6	Imiglucerase 800 U/2 weeks	GBA: L444P D409H	N	Gibbus	NP	Visual acuity 1.0 R, 1.0 L, slow horizontal saccades, impaired horizontal OKN, impaired VOR	108
6b	7/7	NK	Imiglucerase 2,400 U/2 weeks	GBA: L444P D409H	Mild cognitive impairment	Mild chronic obstructive lung disease	Discrete unspecific white matter changes	Visual acuity 1.0 R, 0.8 L, low horizontal saccades, slow downward vertical saccades, impaired horizontal OKN, discrete impaired VOR	85
7	6/33	Oculomotor disturbance (not specified), 30 Epilepsy, 10	Imiglucerase 2,800 U/2 weeks, zonisamide 100 mg 2-0-3, citalopram 20 mg 1-0-0, clonazepam 0,5 mg 1/2-0-1, valproate 300 mg 1-0-2	GBA: G202R D409H	Stance and gait ataxia, epilepsy, myoclonus, spasticity, psychotic symptoms	Hepatomegaly, obstructive sleep-apnea syndrome, neurodermatitis	Unspecific white matter changes	Visual acuity 0.8 R, 0.8 L, horizontal saccade paresis L > R, slow abduction > adduction bilaterally, prolonged latency of horizontal saccades, slow vertical saccades, mild impaired smooth pursuit, impaired horizontal OKN	71
8	2/2	Retarded motor development, 29, Oculomotor disturbance (not specified)	Imiglucerase 3,200 U/2 weeks, levetiracetam 3,000 mg/day, lamotrigine 200 mg/day oxcarbazepine 2,400 mg/day	GBA: L444P L444P	Epilepsy, cognitive impairment, dystonia, stance and gait ataxia, pyramidal signs, clonus bilateral, hypomimia	St.p. spleen resection, femoral head necrosis, pathological right femur fracture, fixed kyphosis, restrictive lung disease	Discrete ventricle enlargement	Visual acuity 0.63 R, 0.63 L, horizontal saccade paresis, impaired horizontal OKN	68
9c	1/1	Retarded motor development, 16, Oculomotor disturbance (not specified)	Imiglucerase 4,400 U/2 weeks	GBA: L444P L444P	Stance and gait ataxia, spasticity, hyperreflexibility, dysarthria, dystonia, cognitive impairment	Fixed kyphosis	N	Slow horizontal saccades, slow downward vertical saccades, impaired horizontal and downward OKN, impaired VOR, head thrusts, operatively corrected squint, abducens palsy bilaterally R > L	60
10c	0/prenatal	Retarded motor development, 8, Oculomotor disturbance (not specified)	Imiglucerase 2,000 U/2 weeks	GBA: L444P L444P	Stance and gait ataxia, hyperreflexibility, dystonia, dysarthria, discrete cognitive impairment	Gibbus	NP	Operatively corrected squint R, esotropia R, visual acuity 0.8 R, 1.0 L, complete bilateral abducens palsy, primary position upbeat nystagmus, horizontal and vertical slow saccades, impaired horizontal smooth pursuit, impaired horizontal OKN, bilateral impaired VOR, head thrusts	60
11b	7/7	NK	Imiglucerase 2,000 U/2 weeks	GBA: L444P D409H	N	N	N	Visual acuity 1.0 R, 0.63 L, low horizontal saccades, discrete slow downward vertical saccades, impaired horizontal OKN, discrete impaired vertical smooth pursuit, discrete head thrusts	111
PATIENTS MEASURED AT 1 TIMEPOINT
Patient no./sex/age	Age of onset/age diagnosis	First symptom observed, age (years)	Medication	Genotype	Neurologic and psychiatric findings	Internal manifestation	MRI findings	Oculomotor findings (pathological)	IQ
12	6 months/4	Oculomotor disturbance, 6 months	Imiglucerase 2,400 U/2 weeks	GBA: L444P L444P	N	Hepatosplenomegaly, chronic obstructive lung disease	N	Slow horizontal saccades with looping, impaired VOR leftward > rightward, impaired horizontal OKN	131
13	21/21	Epilepsy, 15	Imiglucerase 3,200 U/2 weeks, lamotrigine 600 mg/day, levetiracetam 1,000 mg/day, 10 gtt salbutamol, dimethindene 4 mL/day	GBA: N227S L424P	Epilepsy	Osteomyelofibrosis with trombocytopenia, neurodermatitis, allergic reaction on the imiglucerase therapy	N	Visual acuity 1.0 R, 1.0 L, discrete slow horizontal saccades, saccadic vertical smooth pursuit	114
14	6/10	Oculomotor disturbance, 6	Imiglucerase 3,400 U/2 weeks	GBA: IVS2 + 1G > A R463C	N	Hashimoto thyroiditis, hepatosplenomegaly	St. p. petrous bone cholesterol granuloma removal	Visual acuity 1.0 R, 0.63 L, slow horizontal saccades with “looping,” borderline slow vertical saccades, pathological VOR	124
15	2/4	Hepatosplenomegaly 4, Oculomotor disturbance, 8	Imiglucerase 2,800 U/kg	GBA: L335V L335V	Postural and extremity cerebellar ataxia, hypotonus, dyscalculia	Mild hepatosplenomegaly	Hypointensities in pallidum and thalamus	Visual acuity 0.63 R, 0.63 L, ptosis L with a Cogan-Twitch, abduction deficit L > R, abnormal smooth pursuit with “looping” upwards, horizontal slow abducting > adducting saccades, vertical slow saccades with “looping,” mild head thrusts, horizontal OKN present, but saccades impaired, impaired VOR with extremely slow compensatory eye movement, intact visual fixation-suppression of the VOR	81
16	1 month/17 months	Hepatosplenomegaly, 1 month	Velaglucerase 1,600 U/2 weeks	GBA: R359Q RecΔ55	N	Hepatosplenomegaly, generalized lymphadenopathy, hypotrophic habitus, trombocytopenia, neonatal ikterus, atopic eczema, ichtyosis simplex, st. p. anaphylactic reaction after the ninth dose of enzymatic therapy	NP	Visual acuity 0.7 bilaterally, impaired smooth pursuit vertically > horizontally, borderline impaired horizontal saccades	NP
17	6 months/6 months	Hepatosplenomegaly, 6 months	Imiglucerase 2,800 U/2 weeks, carbamazepine 900 mg/day, valproate 500 mg/day	GBA: L444P L444P	Epilepsy with a complex symptomatology, myoclonia, dyscalculia	Hepatosplenomegaly, gibbus, osteopenia, kyphoscoliosis with a thoracolumbar deformity	N	St. p. partial vitrectomy R, visual acuity 0.5 R, 0.8 L, low horizontal and downward vertical saccades, impaired vertical smooth pursuit, decreased vertical OKN, pathological VOR leftward > rightward	MoCA: 28/30
18	7/7	Oculomotor disturbance, 7 Epilepsy, 22	Imiglucerase 60 U/kg/2 weeks	GBA: L444PRecTL	Epilepsy, anxiety attacks, generalized hyperreflexia, discrete spasticity with positive Babinsky and slow rapid movements on the right foot, anxiety, depression	–	Medullary infiltration of the pontine, basin, femoral and tibial bones bilaterally	Convergent strabismus, anamnestic initially complete horizontal saccade palsy, at the time of examination slow horizontal saccades performable, bilateral abducens palsy, slow upward saccades, downward saccade palsy, blinking	NP
19	18/1	Diagnosis established on the basis of the diagnosis of his sister, first symptoms appeared at age 18	No therapy	GBA: L444PRecTL	Manic behavior, anxiety and depression	Splenomegaly	Medullary infiltration of the spine	Convergent strabismus, slow horizontal and downward saccades, pathological VOR	NP
20	3/19	NK	Imiglucerase, levetiracetam	GBA: L444P L444P	Epilepsy, facial dystonia, nasal speech, wide-based gait	Scoliosis, splenectomy due to spleen rupture, interstitial lung disease, abnormal bone marrow findings in MRI	NP	Convergent strabismus, pathological VOR	NP
21	12/27	Epilepsy, 12	Miglustat 300 mg/day, valproic acid 2,000 mg/day, clonazepam, bromazepam, phenobarbital 200 mg/day, zonisamide	GBA: L444P D409H	Becker disease, axonal neuropathy, myoclonic epilepsy, mild facial dystonia, tremor, extremity ataxia, hyperreflexia, no Babinski, no muscle weakness	Moderate hepatosplenomegaly, scoliosis, uncle and brother suffer from Becker’s muscular dystrophy	NP	Horizontal supranuclear saccade palsy with blinking and head thrusts	NP
22	1/1	Hepatosplenomegaly, 1	Imiglucerase 60 U/kg, carbamazepine, paroxetine, valium 60 U/kg, baclofen	GBA: L444P D409H	Myoclonic epilepsy, difficulty opening mouth, wide-based gait, axial and extremity ataxia, facial dystonia with dystonic tremor, hyperreflexia, no Babinski, high arches, hammer toes, mild lower extremity dysmetria, depression, paroxysmal aggression	Kyphosis, bone pain	Normal MRI	Convergent strabismus	NP
23	13 months/13 months	Hepatosplenomegaly, 2	Velaglucerase alfa 60 U/kg	GBA: D409H D409H	–	Hepatosplenomegaly, Turkish origin, two uncles of his father died of Gaucher disease	NP	Horizontal supranuclear saccade palsy with blinking	NP
24	1 month/18 months	Stridor and early psychomotor delay, 1 month	Imiglucerase	GBA: D409H IVS2 + 1G > A	Early psychomotor delay, walking not possible, can stand up with support, facial, cervical and acromioclavicular dystonia	Hepatosplenomegaly, stridor (diminishing under the therapy) from birth on, Cambodian origin. BAER abnormal with normal hearing	NP	Complete gaze palsy, convergent strabismus	NP
25	18 months/3 years	Early developmental delay 18 months, stance and gait ataxia, 5	Ambroxol 80 mg/day	GBA: R163X I260T	Myokimia, myoclonus, dystonia, startle, cloni, loss of walking ability with instability and sudden falls. Loss of speech	Nigerian origin. Hepatosplenomegaly, iron deficiency, thalassemia minor, microcytic anemia. Under therapy with imiglucerase worsening of ataxia, speech and myoclonic epilepsy with a progressive deterioration. Anamnestic reported improvement of the speech (saying words such as Maman or Au revoir), fine (playing with toys) and gross motor function (walking)	NP	Complete gaze palsy with convergent bilateral esotropia, abducens nerve palsy bilaterally	NP
26	1 month/1 year	Stridor and early developmental delay, 11 months	Ambroxol 40 mg/day	GBA: G377S c.141ΔAG	Developmental delay, gross motor impairment, dysphagia with growth retardation	Algerian origin. Hepatosplenomegaly, bronchial congestion with chronic stridor and cough	NP	Convergent squint	NP

BAER, brainstem acoustic evoked responses; L, left; N, normal findings; NK, not known; NP, not performed; MRI, magnetic resonance imaging; MoCA, Montreal Cognitive Assessment; OKN, optokinetic nystagmus, R, right; VOR, vestibulo-ocular reflex.

^a,b,cIndicated patients are siblings.