Table 7 MLD first signs and symptoms from previous studies and complementary caregiver language from our existing study
| Â | Previous studies | Complementary findings from our caregiver-reported survey | ||||
|---|---|---|---|---|---|---|
Source | Data point | Sample size | Supporting results | Sample size | Supporting caregiver language | |
Late infantile | Kehrer et al. [25] | In late infantile patients, 91.0% exhibited only motor symptoms | 35 | In late infantile patients, 95.0% were observed with early signs of coordination difficulties, clonus/tremor, and/or vision changes | 20 | Late infantile MLD caregiver language: early physical signs |
Coordination difficulties  Delayed walking, difficult walking, strange posture  Delayed when walking, many falls, gait sluggish  Early to crawl, but late to stand up and hold onto things  Has never been able to walk freely, twisted foot while walking  Never walked, left was weaker than her right side  Not progressing with walking (started taking first steps but did not progress after)  Problems with motor development  Slow motor skills  Stagnation of motor development  Started to lose balance  Struggled to run- uncoordinated, clumsy, started walking late as a baby  Trouble walking  Unstable sitting, walking  Unsteady gait  Wasn’t getting on the couch anymore  Wasn’t walking Clonus/tremor  Clonus  Developed a small tremor in hands  Shake really bad after naps, foot tremoring  Slight tremor  Slight tremor, eye lid twitching (that pediatrician noticed on regular checkup)  Tremors  Very mid absences Changes in vision  Strabismus, nystagmus  Sudden squint  Went cross-eyed overnight | ||||||
Kehrer et al. [25] | In late infantile patients, 9.0% exhibited motor and cognitive symptoms | 35 | In late infantile patients, 10.0% were observed with both physical and cognitive/behavioral early symptoms | 20 | Late infantile MLD caregiver language: early physical + cognitive/behavioral signs | |
 Slower than average child, wasn't walking, only 6 words, regressing  Early to crawl, but late to stand up and holding on to things, gaps between achieving milestones was getting bigger | ||||||
Fumagalli et al. [3] | 95.0% of late infantile subjects had a GMFC-MLD score > 1 (inability to walk independently) at 36 months | 22 | 25.0% of late infantile patients were observed with development delays | 20 | Late infantile MLD caregiver language: developmental delays in walking | |
 Delayed walking, difficult walking, strange posture  Delayed walking, many falls, gait sluggishness  Early to crawl, but late to stand up and holding on to things  Late walker, walking was stiff, often fell  Slower than average child, wasn't walking | ||||||
Harrington et al. [16] | 75.0% of late infantile patients experienced problems with gross motor function as initial symptom | 16 | 90.0% of late infantile patients were reported with early signs of coordination difficulties | 20 | Late infantile MLD caregiver language: gross motor function | |
 Delayed walking, difficult walking, strange posture  Delayed when walking, many falls, gait sluggish  Early to crawl, but late to stand up and hold onto things  Has never been able to walk freely, twisted foot while walking  Never walked, left was weaker than her right side  Not progressing with walking (started taking first steps but did not progress after)  Problems with motor development  Slow motor skills  Stagnation of motor development  Started to lose balance  Struggled to run- uncoordinated, clumsy, started walking late as a baby  Trouble walking  Unstable sitting, walking  Unsteady gait  Wasn’t getting on the couch anymore  Wasn’t walking | ||||||
Harrington et al. [16] | 68.8% of patients in the late infantile group never learned to walk independently | 16 | 30.0% of late infantile patients were reported to have development stagnation | 20 | Late infantile MLD caregiver language: developmental stagnation | |
 Could never walk independently  Development not progressing  Has never been able to walk freely  Not progressing with walking (started talking first steps but did not progress after)  She never walked  Stagnation of motor development | ||||||
Harrington et al. [16] | 62.5% of late infantile patients presented with fine motor or related symptoms (i.e., eye movement, eating or swallowing and hand tremors) pre-diagnosis | 16 | 25.0% of late infantile patients were reported to have clonus/tremors 15.0% of late infantile patients were reported to have vision changes | 20 | Late infantile MLD caregiver language: early fine motor signs | |
Clonus/tremors  Clonus  Developed a small tremor in hands  Shake really bad after naps, foot tremoring  Slight tremor  Slight tremor, eye lid twitching (that pediatrician noticed on regular checkup)  Tremors  Very mid absences Changes in vision  Strabismus, nystagmus  Sudden squint  Went cross-eyed overnight | ||||||
Beerepoot et al. [18] | The development of strabismus either clearly before, simultaneously with or shortly after gross motor symptom onset was reported exclusively in patients with a late infantile MLD form (27.0%, 17/63) | 63 | 15.0% of late infantile patients were reported to have vision issues. All cases were reported in combination with coordination difficulties | 20 | Late infantile MLD caregiver language: vision + gross motor early signs | |
 Strabismus, nystagmus, slow motor skills  Unsteady gait, sudden squint (18 months)  Went cross-eyed over night and started to lose her balance | ||||||
Juvenile | Kehrer et al. [25] | In early-juvenile patients, 61.0% exhibited only motor symptoms | 18 | In juvenile patients, 72.7% were observed with early signs of coordination difficulties, clonus/tremor, and/or vision changes | 11 | Juvenile MLD caregiver language: early physical signs |
Coordination difficulties  Abnormal gait  Broad-based gait  Loss of balance, tripping  Pain when walking, motor problems indicated by the teacher  Unstable walking, never able to ride a bike Clonus/tremor  Arm movement as if after a stroke  Hand tremors | ||||||
Kehrer et al. [25] | In early-juvenile patients, 39.0% exhibited motor and cognitive symptoms | 18 | In juvenile patients, 18.2% were observed with both physical and cognitive/behavioral early symptoms | 11 | Juvenile MLD caregiver language: early physical + cognitive/behavioral signs | |
 Ability to do math, top of his class in 1st grade, 2nd grade couldn't monitor progress and didn't know he was struggling, 3rd grade couldn't add, struggled to run- uncoordinated, clumsy, started walking late as a baby  Difficulty learning (learning vocabulary), abnormal gait, obstinate  Lack of concentration, issues with concentration levels, very mild absences, little bit of regression (not age-appropriate behavior)  Loss of balance, tripping, severe fatigue, nighttime awakenings | ||||||
Harrington et al. [16] | For juvenile patients, 56.3% had first symptoms related to changes in cognitive function | 16 | 54.5% of juvenile patients reported initial comprehension challenges | 11 | Juvenile MLD caregiver language: early signs of comprehension challenges | |
 Ability to do math, top of his class in 1st grade, 2nd grade couldn't monitor progress and didn't know he was struggling, 3rd grade couldn't add  Difficulty learning (learning vocabulary)  Forgetful- getting lost  Lack of concentration, issues with concentration levels  Regression in writing | ||||||
Harrington et al. [16] | 43.8% of juvenile patients had first symptoms related to social/behavioral function | 16 | 45.5% of juvenile patients were reported with changes in behavior/ personality | 11 | Juvenile MLD caregiver language: early signs of behavioral/personality changes | |
 Behavioral disorders  Obstinate  Peeing pants in school  Personality changes, impulsive behavior, issues with sleep, loss of interest in activities that […] used to be interested in | ||||||
Harrington et al. [16] | By the time of diagnosis, 56.3% of the patients with juvenile MLD had also experienced some decline in gross motor function | 16 | 54.5% of juvenile patients were reported with developmental regression as an initial symptom | 11 | Juvenile MLD caregiver language: developmental regression | |
 Ability to do math, top of his class in 1st grade, 2nd grade couldn't monitor progress and didn't know he was struggling, 3rd grade couldn't add, struggled to run- uncoordinated, clumsy, started walking late as a baby  Forgetful- getting lost, peeing in pants at school  Little bit of regression (not age-appropriate behavior)  Personality changes, impulsive behavior, issues with sleep, loss of interest in activities that […] used to be interested in  Loss of balance, tripping, severe fatigue, nighttime awakenings  Regression in writing | ||||||