Normalized MANE/map notationNM_018489.3:c.5138_5139del · NP_060959.2:p.Ser1713Cysfs*3 — The reviewed report uses NM_018489.2. NM_018489.2 and MANE Select NM_018489.3 use the same coding coordinate here, so c.5138_5139del and p.Ser1713Cysfs*3 map 1:1.
A girl in the 6–10 age group with strong social connection and a fluctuating history involving language access, motor planning, vision, movement, sensory regulation, illness-linked changes, ENT findings, and reported treatment-associated changes
A 2025 caregiver document described her as a conversational and socially connected school-age girl who is caring, affectionate, empathetic, interactive, and often shy when first meeting someone. It also described friends and playdates, a desire to participate with the people around her, and engagement in many parts of daily life.
At the 2025 family update, she attended a regular private-school classroom without one-to-one support, and her family reported no significant behavior problems at school. She received physical, occupational, and speech-language therapy and participated in a school social-dyad or play group that began in 2024. Therapy and school reports document meaningful gains in bilateral coordination, handwriting, peer play, turn-taking, flexibility, pretend play, reporting, and emotion labeling.
Her communication profile is easy to underestimate because she speaks fluently and had broadly average or stronger early vocabulary and core-language scores. Her more persistent needs appear when language, attention, motor planning, social interpretation, visual processing, and executive function must operate together. Word finding, organizing an explanation, maintaining a topic, inferring another person’s perspective, entering an unstructured interaction, and reformulating a sentence can all become harder under load.
Her family also sees a major difference between her usual baseline and an off-baseline state. When well, she is engaged, social, flexible, and communicative. During illness, poor sleep, sensory overload, visually moving environments, or other periods of strain, her balance, movements, language access, auditory and sensory processing, emotional regulation, rigidity, frustration tolerance, and ability to complete schoolwork may worsen together. Recovery can take weeks. Her family describes these as reversible dips from which she later recovers, not a continuous loss of previously acquired skills. Those episodes do not define her personality or erase her substantial progress.
02
Molecular diagnosis
A GeneDx Autism/Intellectual Disability Xpanded Panel reported a heterozygous pathogenic frameshift variant in ASH1L, NM_018489.2:c.5138_5139del, p.(Ser1713Cysfs*3). The sample was collected in March 2023 and the report was issued in April 2023, around age four.
The result was de novo: both parents tested negative, and parentage was confirmed. Germline mosaicism cannot be completely excluded, so the result does not make recurrence risk zero.
The two-base deletion shifts the reading frame at codon 1713, changes the first affected amino acid from serine to cysteine, and introduces a premature stop three codons into the new reading frame. This is one heterozygous frameshift, not a “double frameshift.” The laboratory classified it as pathogenic. No patient-specific RNA, protein, or cellular study was available in the reviewed materials to establish precisely what happens to the altered transcript in her cells or which individual clinical findings it explains.
GeneDx also reported adequate coding-region coverage and no multi-exon ASH1L deletion or duplication in the sequence data. As with any panel, that does not exclude every possible genetic mechanism. No separate diagnostic genetic co-finding was established in the reviewed materials.
Chapter 02Development, communication, and movement
03
Early development and emerging differences
Her early developmental differences were subtle. She did not qualify for early-intervention services when first evaluated. Formal therapy histories later record torticollis treated beginning at approximately four months and physical, occupational, speech-language, and feeding therapy. Her family recalls crawling at approximately 11.5 months and walking at approximately 15 months.
An older family history also described mild infant stridor that resolved, tiring or repeatedly popping off during breastfeeding, low bottle volumes with frequent feeds, and unreleased tongue ties. Her family remembers high-pitched squealing and unusual laughter in infancy; both later resolved. They also recall body tremors becoming noticeable after one round of infant vaccinations. The family itself has emphasized that temporal proximity does not establish that vaccination caused the tremors.
Her caregiver has wondered whether early difficulty maintaining floor postures, rotating through the trunk, moving into tall kneeling, crawling, pushing up, coordinating both hands, shifting attention, and planning movement made exploratory play unusually effortful and indirectly reduced opportunities to practice higher-level social and language skills. Her early play was functional, but her family later recognized that symbolic or flexible pretend play was not as robust as expected. The proposed developmental connection is a family hypothesis, not a proven mechanism. Later school speech-language records document gains in pretend play, flexibility, and peer interaction.
04
Speech, language, pragmatics, and executive access
Her early formal language profile showed substantial strengths.
At approximately three years six months, the CELF Preschool–3 produced broadly average composite scores:
Speech, language, pragmatics, and executive access
Measure
Standard score
Core Language
95
Receptive Language
94
Expressive Language
90
Language Content
93
Language Structure
91
Academic Language Readiness
90
At approximately age three, receptive vocabulary was 114, or the 83rd percentile, and expressive vocabulary was 121, or the 92nd percentile. Speech intelligibility was 89.7%, mean length of utterance was 3.79, and pragmatic skills were considered age appropriate once her attention was secured. Following Directions and Word Structure were relative weaknesses at approximately the 16th percentile.
In 2024, the Preschool Language Assessment Instrument placed Matching and Selective Analysis at the 75th percentile, Reordering at the 37th percentile, and Reasoning at the 50th percentile. The evaluator explicitly stated that recommendations were offered because the family wanted useful targets, not because that observation demonstrated a broad language deficit.
By the final 2025 school speech-language report, the more specific higher-level and pragmatic difficulties were clearer. Her CELF-5 Pragmatic Profile scaled score was 5, below average. Areas of difficulty included:
maintaining a topic;
entering and leaving interactions;
participating in unstructured groups;
making introductions or giving advice;
responding to teasing or failure;
interpreting nonverbal social and emotional information;
using greetings consistently; and
judging interpersonal distance.
The same report documented real progress in peer play, turn-taking, flexibility, pretend play, reporting experiences, and labeling emotions. Remaining challenges included transitions, moments of freezing or eye aversion, and communicating with less-familiar partners. Speech-language therapy one to two times weekly was recommended.
At the latest family update, she remained conversational and socially interested but continued to have word-finding difficulty, mid-sentence reformulation, deeper semantic and higher-level language challenges, perspective-taking and inferencing difficulty, and trouble organizing explanations. Executive-function demands—planning, starting, sequencing, holding several steps in mind, and following through—can further restrict access to skills she possesses. Letter reversals and possible dyslexia features have also been noticed. A neuropsychological evaluation was planned, but no completed neuropsychological or reading-disorder report was available.
Her family does not identify childhood apraxia of speech as her communication profile. A 2022 speech-language history records that neurology did not find that she met autism criteria and instead described complex motor stereotypies unrelated to autism; the original neurology note is unavailable. Her family later reiterated that she did not clearly meet autism or ADHD criteria. “Suspected ADHD” has appeared as a working description, but the current records do not establish ADHD as a completed diagnosis. The ASH1L result should not itself be treated as an autism diagnosis.
05
Occupational therapy, tone, coordination, and motor planning
Her formal motor record shows changing performance across time and task rather than one uniform level of impairment.
In a July 2022 occupational-therapy evaluation:
PDMS-2 Grasping and Visual-Motor Integration were each at the 16th percentile;
the SPM-P fell in the “Some Problems” range for hearing, touch, body awareness, and total sensory processing and in the “Definite Dysfunction” range for planning;
the Little DCDQ score was 49/75, a screening result considered suspicious for developmental coordination disorder, not a diagnosis; and
residual asymmetry and stiff movement were observed, while tone was described as functionally within range that day.
That wording is important. Although family summaries have sometimes used “low tone,” the 2022 OT evaluation did not establish persistent generalized hypotonia.
A 2024 OT evaluation documented difficulty maintaining prone extension or supine flexion without assistance, poor balance, sequencing and coordination difficulty, asymmetry, inconsistent crossing of the midline, and marked oculomotor difficulty. Beery testing in December 2024 showed:
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Occupational therapy, tone, coordination, and motor planning
Measure
Standard score
Percentile
Visual-Motor Integration
80
9th
Visual Perception
88
21st
Motor Coordination
81
10th
The record also shows measurable improvement. An OT progress report documented throwing accuracy increasing from approximately 10% to 50%, kicking from 0% to 66%, and cross-body performance from 20% to 80%. Residual needs involved handwriting, motor planning, sequencing and processing, and sensory filtering.
In October 2025, school OT reported improved bilateral coordination, spontaneous use of both hands, handwriting, and work with peers. She completed an eyes-closed head-tip activity independently on approximately 80% of opportunities. No formal reflex assessment had been completed, so improvement in that activity should not be presented as proof that a particular reflex had been “integrated.”
Her ability to participate successfully in everyday, school, peer, and therapy activities coexists with these formal needs. Skill is task-specific: practice, visual conditions, motivation, fatigue, and the type of motor sequence all matter.
06
Left-sided differences, vision, and visually triggered load
A May 2023 functional-vision evaluation found 20/20 uncorrected acuity in each eye and binocularly, smooth pursuits, and accurate saccades. It also found mildly reduced accommodation, reduced convergence and divergence ranges and reserves, and delayed performance on Copy Forms. The accompanying eye letter identified binocular dysfunction and anisometropic hypermetropia greater in the left eye and recommended updated glasses and home vision therapy.
The 2023 finding of smooth pursuits is not necessarily inconsistent with the marked oculomotor difficulty seen during the 2024 OT evaluation. The assessments occurred in different settings, at different times, and under different task demands.
Her family reports that she has worn glasses since 2022, with an approximate prescription of +0.50 in the right eye and +3.50 in the left at one point. They also report intermittent visual suppression, sensitivity to visual motion, a compensatory body position that can favor the right eye, and increased difficulty with screens, scrolling, optic flow, and car travel. Those later details are caregiver observations rather than values from the 2023 eye letter. A current ophthalmology report is still needed to confirm refraction, suppression, amblyopia status, and the clinical meaning of the posture.
The family's observations show a repeated context-dependent pattern:
Left-sided differences, vision, and visually triggered load
Context
What the family may observe
Screens, scrolling, optic flow, or a visually moving environment
More distal movements, visual discomfort or overload, altered posture, or reduced organization
Car travel or intense motion such as a roller-coaster-type experience
Increased movement or imbalance, visual-motion sensitivity, and sometimes marked dysregulation
High sensory or cognitive demand
More motor overflow, word-finding or planning difficulty, frustration, and reduced flexibility
Respiratory or viral illness, especially with poor sleep
A broader temporary shift involving balance, sensory and auditory processing, language or executive access, emotion regulation, rigidity, and schoolwork tolerance
Her usual baseline
Greater social engagement, flexibility, communication, and access to learned skills
These are longitudinal caregiver observations, not standardized provocation tests. The repeated timing makes the contexts useful for recognition and support, but it does not prove which visual, vestibular, motor, immune, sleep, or neural mechanism is responsible.
Chapter 03Neurology, regulation, sleep, and ENT
07
Complex movements and the seizure question
Her family describes complex, distal movements involving the hands, ankles, or toes, often more noticeable on the left. During one EEG event-button episode, repetitive arm and hand movements occurred with jaw opening. Her family also reports brief freeze-like moments and intermittent changes in posture around some movement episodes. The movements can become more visible with sensory, cognitive, or visual demand, including screens, scrolling, optic flow, moving environments, car rides, and other experiences with intense visual motion.
Two family communications seeking ASH1L scientific input add useful context. In 2025, her caregiver described the marked arm-and-hand event with jaw opening, freeze-like movements, covering her eyes around unfamiliar adults, and severe tantrum-like episodes without an obvious immediate trigger. The researcher explicitly said that he was not a clinician or EEG specialist and did not interpret the tracing. In a more detailed 2026 clinical summary, her caregiver emphasized the left-predominant hand, ankle, and toe movements; activation during visual, sensory, or cognitive overload; full-time glasses; pursuit and binocular-integration concerns; visual-motion sensitivity; and a right-eye-favoring posture. She asked whether several systems might be interacting rather than assuming that one diagnosis explained the pattern. The researcher replied that circuit-level ideas could be worth studying but that the mechanism remained unresolved and could involve more than one system. Those exchanges generated research questions; they did not establish a movement, seizure, immune, or basal-ganglia diagnosis.
The family reported in May 2025 that the movements had calmed somewhat but remained clearly present. A teacher asked whether they could represent Tourette syndrome; the family says a psychologist felt they did not. The available history has used terms such as complex motor stereotypy, hand flapping, motor overflow, or tic-like movement, but it does not establish Tourette syndrome, dystonia, myoclonus, or another single movement-disorder diagnosis.
There are also two apparently different family observations that should remain visible. During a 2025 cephalexin course, fewer stereotyped movements were noticed. A 2026 parent-authored clinical briefing, however, stated that the complex motor stereotypy itself did not change across states. This may reflect different observation windows, a change in other behaviors rather than the movement itself, or genuine fluctuation. The records do not resolve it.
A formal 24-hour ambulatory EEG in July 2024 captured wakefulness, drowsiness, stage 1 and stage 2 sleep, slow-wave sleep, and REM sleep. Her caregiver reports that it was performed at home with continuous video. The tracing was well organized. The report found no focal abnormality, persistent asymmetry, epileptiform discharge, clinical seizure, or electrographic seizure; the single-channel ECG showed normal sinus rhythm. Target movements were recorded without an electrographic correlate and were interpreted as stereotypies or hand flapping.
Her family reports that neurology reviewed the study again in September 2025 and considered it normal, including its sleep architecture. This is reassuring for the recorded events and argues against labeling them as seizures. It does not determine the cause of every movement or guarantee that any different future event would be nonepileptic. No confirmed epilepsy diagnosis is established. During that follow-up period, her caregiver asked whether repeating a home EEG during a severe illness-linked flare might be informative; no later flare-state EEG report is available.
The family later reported a quantitative EEG or “brain-map” study that they were told showed excess slow-frequency activity. The report, recording conditions, measurements, normative method, and specialist interpretation were not available, so that statement cannot be verified or compared directly with the formally reported ambulatory EEG.
Three family-linked movement videos were referenced but were unavailable for review. No finding should be inferred from them unless the recordings are obtained and reviewed with their dates and contexts.
08
Sensory processing, emotional regulation, and state changes
Sensory-processing disorder, anxiety not otherwise specified, nail or surrounding-skin picking, complex motor stereotypy, PANS/PANDAS, visual or oculomotor dysfunction, and suspected ADHD have all appeared as diagnoses or working labels in family materials. The underlying reports are uneven, so they should not be treated as one settled diagnostic formulation.
Her family describes a calm, engaged, flexible, social baseline that may last for weeks or months. Off baseline, she may escalate rapidly, become rigid or intensely frustrated, appear overloaded or fight-or-flight in her response, oppose or refuse tasks she can ordinarily do, scribble instead of completing work, collapse to the floor, scream, or have difficulty recovering. Auditory and sensory processing, balance, language access, executive function, and schoolwork tolerance may worsen at the same time. These episodes are especially associated with illness and sleep loss and can take weeks to resolve. Her family's 2026 clinical summary emphasized that this is a state change from her baseline, not a description of her everyday character.
Some of her most severe car meltdowns occurred at approximately ages four and five and specifically when her younger sibling was also in the car. Her family felt the additional sound, movement, and social demand was the final part of an already overloaded sensory environment. This pattern had improved substantially by approximately age seven.
Picking at nails and surrounding tissue has at times been significant. In one family update, a toenail had been picked until it was hanging loose. This is relevant to skin safety and regulation, but it does not by itself establish an obsessive-compulsive, dermatologic, or self-injury diagnosis.
The contrast between home or illness-related dysregulation and her generally successful school participation is important. The absence of major school behavior problems does not mean that the underlying motor, sensory, executive, or language effort is absent, and an intense flare does not describe her everyday personality.
09
Sleep, illness-linked state, and recovery
The family recalls that illness-linked dysregulation was most obvious from approximately ages one through four and is now seen mainly when she is ill. They believe sleep deprivation during respiratory or other illnesses contributes substantially to her behavioral and functional flares and report tracking these cycles weekly. Her 24-hour EEG recorded the expected sleep stages and was later described by neurology as having normal sleep architecture.
No polysomnogram, diagnosed sleep disorder, or current sleep schedule was available in the reviewed materials. The history therefore supports a family-observed association between illness or sleep loss and state worsening, not a defined primary sleep disorder.
10
Brain MRI, sinuses, mastoids, adenoids, hearing, and vomiting with respiratory illness
A caregiver-transcribed September 2022 MRI report described the brain as structurally normal. It also mentioned a 4 mm right medial temporal diffusion finding considered artifact, patchy ethmoid and maxillary sinus mucosal thickening, a right mastoid effusion with near-complete opacification, left mastoid mucosal thickening, and mild adenoidal hypertrophy. The original signed radiology report and images were unavailable, so this summary follows the family’s transcription.
The transcribed MRI does not describe basal-ganglia inflammation. Later family or advocacy references to suspected basal-ganglia inflammation arose in the PANS/PANDAS context and should not be presented as an imaging finding.
Before surgery, her family remembers chronic mucus or congestion, drooling, snoring, and sleep disruption. They report that the adenoids were later described by ENT as “massive” and “chronic” and were removed in August 2023. Her tonsils remain intact. The operative report is unavailable, and there is no interval imaging showing whether the sinus or mastoid findings resolved, persisted, or recurred.
The family reports normal hearing, but the audiology report and ear-specific thresholds are unavailable. The current information therefore neither documents hearing loss nor independently verifies the reported normal result.
When she has a cough, mucus, or another respiratory illness, coughing may trigger vomiting. This is a direct family observation. It does not establish reflux, cyclic vomiting, aspiration, or a chronic gastrointestinal disorder.
Chapter 04Feeding, infection, and testing
11
Feeding, oral-motor function, palate, frenula, and teeth
A 2022 speech-language report summarized a 2021 feeding evaluation that described oral hypersensitivity to imposed input, reduced jaw strength and cheek use, and concern about tongue-jaw dissociation, possibly in relation to tethered tissue. Feeding therapy ended after approximately four months. A 2022 oral examination described restricted maxillary labial and lingual frenula and a high palate.
Her family recalls that, in infancy, she tired or repeatedly popped off during breastfeeding, took small bottle volumes with frequent feeds, and had substantial gas. They felt that a formula change at approximately three months improved the gas. Mild infant stridor was also reported and later resolved. These are family observations; no infant swallow study, aspiration diagnosis, or structural airway diagnosis is available.
Her family reports timely introduction of solids and straw drinking. Different family summaries place the first tooth at approximately 18–19 months, and the last primary tooth arrived by approximately age three. Before and during that period, the lack of incisors made a typical bite-and-pull pattern difficult, and she used a suck-based or “suck-munch-chew” compensation. Chewing became more typical after approximately four months of feeding therapy. The mild tongue ties were not released.
Her family reports no current swallowing or food-transport problem and describes her appetite and later growth as normal.
12
Gastrointestinal history and stool testing
Her current history is not one of established chronic constipation. Her family reports daily or sometimes more frequent stooling, a normal appetite, and no ongoing feeding or swallowing problem; dairy or other diet changes have sometimes been associated with pebble-like stool despite continued bowel movements. In one later discussion, urology reportedly wondered whether stool could still be retained despite daily bowel movements, while GI reportedly disagreed. No imaging, cleanout record, or formal constipation diagnosis was available to resolve that difference. At approximately age three, diarrhea was the only physical symptom the family noticed during a period they report was later associated with a positive throat swab for streptococcal infection. During respiratory illnesses, coughing and mucus can also precipitate vomiting as described above.
Two commercial stool panels were performed.
The GI-MAP, collected in February 2023, reported the main listed pathogen, parasite, and virus sections as undetected. A separate part of the panel flagged H. pylori above the vendor threshold, several commensal or opportunistic quantities, elevated beta-glucuronidase and secretory IgA, anti-gliadin IgA above 500, normal calprotectin, and negative occult blood. This is a laboratory-developed functional stool PCR panel. Its vendor thresholds and handwritten annotations do not establish clinical H. pylori infection, celiac disease, microbiome causation, neuroinflammation, or an ASH1L-specific mechanism.
A Doctors Data stool study collected in March 2025 reported:
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Gastrointestinal history and stool testing
Measure
Result
Context shown on the report
Listed pathogen PCR
Negative
No listed pathogen detected
Pancreatic elastase
>500 µg/g
Reassuring against pancreatic insufficiency
Fecal fat
None detected
No fat detected
Carbohydrates
Negative
—
Occult blood
Negative
—
pH
6.5
—
Lactoferrin
1.9 µg/mL
Within the displayed range
Calprotectin
<10 µg/g
Within the displayed range
Lysozyme
677 ng/mL
High; displayed reference <500
Secretory IgA
289 mg/dL
Slightly high; displayed reference 30–275
The report used laboratory-developed testing, and pediatric reference and validation limitations affect interpretation. The mild lysozyme and secretory-IgA elevations do not by themselves diagnose colitis, chronic infection, immune dysregulation, or a cause of her neurologic or behavioral changes. The more conventional inflammatory, digestive, bleeding, and pancreatic markers on this panel were reassuring.
13
Streptococcal illness, reported PANS/PANDAS, and illness-linked flares
Her family reports that at approximately age three, streptococcal infection went unrecognized for about ten days because she had no sore throat or fever. The visible changes were diarrhea, severe irritability, and marked mood shifts. A pediatric throat swab was reportedly positive, and the family recalls that three antibiotic courses were given before a test became negative. The original swab results and treatment records are not available.
Her family says this period marked the beginning of much more prominent behavioral and regulation changes. They report that a clinician subsequently made a PANS/PANDAS diagnosis and that an immunologist supported that framework. They have also reported that basal-ganglia inflammation was suspected. The original PANS/PANDAS or immunology assessment is unavailable, and the MRI transcription describes a structurally normal brain without a basal-ganglia abnormality.
Respiratory and viral illness is now described as the most reliable trigger. In one 2025 sequence, a cold reportedly progressed to a UTI while a severe neurobehavioral flare was underway. A later family letter also described worsening around influenza or another viral illness. Family observations include worsening balance, auditory and sensory processing, emotional regulation, rigidity, aggression or fight-or-flight behavior, school tolerance, and language or executive access, followed by a gradual return toward baseline. The family describes this as a recurring illness-linked flare pattern. It does not independently establish PANS/PANDAS criteria, autoimmune encephalitis, basal-ganglia inflammation, a cytokine disorder, or an ASH1L-specific immune mechanism.
14
Tick-borne and related infectious testing
Across the available reports, Lyme and Bartonella testing was negative; the one distinct positive finding was an isolated relapsing-fever Borrelia genus IgG result in 2024.
Lyme IgM, IgG, and speciation negative; relapsing-fever Borrelia genus IgG and “TBRF Borrelia spp” reported positive; B. miyamotoi, B. hermsii, and B. turicatae negative; Babesia and Bartonella testing negative
October 2025
Lyme IgM and IgG negative by the laboratory’s IGX and CDC/NYS criteria; Bartonella FISH and species IgM/IgG panel negative
October 2025, separate laboratory
Bartonella henselae, B. koehlerae, B. quintana, and B. vinsonii berkhoffii IgG all below 1:32 and nonreactive
The isolated 2024 relapsing-fever Borrelia genus IgG result is distinct from a positive Lyme panel and does not, by itself, establish active infection. The available reports do not support describing Lyme or Bartonella as persistently positive, nor can they show that herbs cleared an infection. The clinical meaning of the TBRF result requires interpretation by the treating clinician in the context of exposure, symptoms, assay performance, and any confirmatory testing.
Urinary observations
Formal urine testing in 2023 was limited:
Tick-borne and related infectious testing — table 2
Date
Findings
June 2023
Specific gravity 1.010, pH 6.5, trace protein and leukocytes; blood, nitrite, glucose, and ketones negative; urine clear
July 2023
Specific gravity 1.015, pH 6.5, trace non-hemolyzed blood, 1+ protein, 2+ leukocytes; nitrite, glucose, and ketones negative; slightly cloudy
July 2023 culture
Mixed organisms; laboratory interpreted the clean-catch specimen as likely urogenital contamination and recommended recollection if clinically indicated
The July specimen did not establish a bacterial isolate. Trace blood appeared on that one dipstick, but recurrent hematuria is not documented, and the available testing does not establish chronic kidney or bladder disease.
In 2025, the family reports one urinary tract infection treated with cephalexin during a broader illness that began as a cold. The diagnostic urine result is not available. This supports one parent-reported treated UTI, not a history of recurrent culture-proven infection. No recurrent urinary, kidney, bladder, or continence disorder is established.
Viral, vaccine-antibody, autoimmune, and inflammatory testing
Testing in August 2023 included:
EBV quantitative plasma PCR: not detected;
HHV-6 IgM: <1:20, not detected;
HHV-6 IgG: 1:80, detected;
varicella IgG: 507.6 IV, positive;
rubella IgG: 16.5 index, positive; and
mumps IgG: 192 AU/mL, positive.
A single detected HHV-6 IgG titer indicates prior exposure or antibody and does not establish acute infection or reactivation. The positive vaccine-related IgG results indicate detectable antibody; they do not, by themselves, decide whether a booster is or is not appropriate.
ANA was <1:80 and negative in 2023. In 2025 it was 1:40 with a homogeneous pattern. The reporting laboratory noted that a low titer can occur in healthy individuals. Because the assays and reporting thresholds may differ, these results do not establish seroconversion or autoimmune disease.
An earlier family-transcribed Mycoplasma IgM value was 295 U/mL, below the report’s stated negative cutoff of 770. In 2024, ASO, DNase B, thyroid testing, and Mycoplasma serology were not abnormal. In 2025, ESR was 2, CRP was <3, ASO and DNase B were negative, and Mycoplasma serology was negative. These later results do not prove or disprove the family-reported streptococcal event at age three, and the record does not establish immune deficiency or chronic systemic inflammation.
Blood chemistry, carnitine, and other conventional laboratory findings
Selected formal results include:
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Tick-borne and related infectious testing — table 3
Period
Result
Context
August 2023
Free carnitine 14 µmol/L
Low; displayed reference 25–55
August 2023
Total carnitine 32 µmol/L
Low; displayed reference 35–90
August 2023
Esterified carnitine 18 µmol/L
Within displayed reference 4–36
August 2023
Esterified/free ratio 1.3
High; displayed reference 0.1–0.8
August 2023
Homocysteine 5.1 µmol/L
Within displayed reference 4.0–15.0
August 2023
Iron 81 µg/dL
Within range; hemolysis prevented calculation of TIBC and saturation
Date not independently confirmed
BUN 26 mg/dL with normal creatinine
High; displayed BUN reference 7–20; remainder of CMP and CBC broadly reassuring; the collection date was not independently confirmed in the available source
TWO REPORTED BUN RESULTS · ONE DATE NOT INDEPENDENTLY CONFIRMED
Two reported BUN values.
This display preserves the reported mg/dL values and interpretations. Only the October 2025 result has an independently confirmed date; the 26 mg/dL result's collection date remains unconfirmed. The list follows source-table order, not a confirmed chronology, and the two points do not establish a continuous trend.
Date not independently confirmed26 mg/dL
Above displayed 7–20 range
Oct 202517 mg/dL
Within the displayed range
The 2025 panel also reported copper, zinc, ceruloplasmin, magnesium, thyroid testing, vitamin B12, and homocysteine within their displayed ranges. No longitudinal hematology assessment is available to show whether the low white-cell and neutrophil values persisted.
Plasma catecholamines in 2023 were epinephrine 314 pg/mL, norepinephrine 524 pg/mL, dopamine <40 pg/mL, and total catecholamines 838 pg/mL. The individual epinephrine, norepinephrine, and dopamine values fell within the report’s pediatric supine limits for ages 3–15; the report did not provide a pediatric comparison range for the total. Collection posture was not preserved, and the norepinephrine analysis required dilution because there was insufficient specimen for undiluted testing. The report also warned that plasma values in small children are strongly affected by stress. These results should not be described as markedly elevated or used to diagnose dysautonomia.
Primary packed-red-cell and trace-element reports contained several minor deviations and warned about specimen contamination and interpretive limitations. The findings do not establish manganese or copper toxicity.
15
Buccal mitochondrial-enzyme testing
A buccal-cell MitoSwab report signed in November 2023 recorded:
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Buccal mitochondrial-enzyme testing
Measurement
Result
Reported comparison
Total buccal protein
371 µg
—
Citrate synthase
27.63 nmol/min/mg
228% of control mean; above displayed reference 4.4–22
Complex IV/citrate synthase
0.118
38% of control mean; below displayed reference 0.15–0.6
Complex I/citrate synthase
6.0
88% of control mean; within displayed reference 3.4–11.9
Complex I/Complex IV ratio
51
Above displayed comparison 12.1–30.3
The central factual distinction is that the complex IV/citrate-synthase ratio was below the report’s range, while the complex I/citrate-synthase ratio was within range.
The report described buccal mitochondrial-enzyme testing as an evolving laboratory-developed assay, stated that it was not FDA approved, noted that complex-I validation was incomplete, and cautioned that buccal tissue may not represent other tissues. It recommended repeat testing within approximately six months; no repeat result was found in the reviewed materials. This assay alone does not diagnose mitochondrial disease or show that an ASH1L variant caused the enzyme pattern, low carnitine, movement, fatigue, or illness-linked changes.
16
Folate-receptor, trace-element, lipid, hair-mineral, and neurotransmitter testing
The 2023 folate-receptor-antibody test did not show a detectable binding antibody. The blocking result was reported as “sFR/see below” because soluble folate receptor interfered with the assay; its clinical significance was unknown. This was not a positive folate-receptor-antibody result.
Additional nonstandard or functional testing included packed-red-cell and trace-element panels, a hair-tissue-mineral analysis, a Prodrome lipid report, a red-cell lipid panel, and urinary neurotransmitter testing. Some reports contained flagged values or proprietary pattern labels. The hair-mineral report used terms such as “slow oxidation” and “heavy metal toxicity” and included nonstandard detoxification and vaccine-avoidance recommendations; the lipid-vendor materials described their reports as educational or research use. These tests do not establish central neurotransmitter concentrations, heavy-metal toxicity, mitochondrial disease, neuroinflammation, prognosis, or an ASH1L-specific mechanism, and their recommendations are not validated ASH1L care guidance.
Chapter 05Treatments, supports, and the whole-person view
17
Medication, supplement, antibiotic, and anesthesia observations
The most striking medication-associated observations were reported during several antimicrobial courses. They should remain separate because the drugs, indications, timing, and observed directions of change were not the same. The first cephalexin observation is supported by a direct caregiver update. The later prolonged-cephalexin, fluconazole, and cefdinir descriptions came from the child-specific section of a July 2026 parent-authored update, but the prescribing records and standardized outcome measures were not available.
Medication, supplement, antibiotic, and anesthesia observations
Exposure
Family-observed course
Cephalexin for a reported 2025 UTI
By approximately day five, her caregiver and another observer noticed better organization, social engagement, attention, language, executive function, and regulation. Fewer stereotyped movements were noticed during that observation window. The immunologist reportedly extended the course.
A later, prolonged cephalexin course
Her family described gains in executive function, memory retrieval, conversational language, social engagement, flexibility, regulation, theory-of-mind tasks, drawing, coloring, singing, and general cognitive access. A later family letter also described a streptococcal illness treated with cephalexin followed by improvements noticed by both family and teacher.
Oral fluconazole
Her family described a similarly broad improvement in attention, executive function, conversational language, social initiation, emotional regulation, flexibility, participation, and daily independence. Examples included getting dressed before camp and brushing her own teeth with fewer prompts.
Cefdinir
Her family reported marked neurobehavioral worsening rather than improvement.
Her family also recalls a similar positive change during an antibiotic course around age three. These reports were not measured with standardized outcomes or blinded comparison, and complete prescribing and laboratory records were not available for every course. The temporal patterns are important to preserve, but they do not prove that an antibiotic or antifungal treated PANS, persistent infection, fungal overgrowth, microbiome dysfunction, inflammation, or an ASH1L mechanism. They are not general treatment recommendations.
Her family reports that methylfolate initially seemed helpful and then stopped helping. SAM-e and folinic acid were later planned, and a subsequent update said folinic acid had been started, but no sustained result was documented. Japanese knotweed, cryptolepis, and cat’s claw were used for presumed tick-borne infection. The family described less of a “constant flare” after approximately six months of herbal treatment and later negative tests, but the original Lyme and Bartonella reports do not establish the claimed infection or clearance. Vitamins, supplements, chiropractic care, and changes in vaccination decisions have also been credited with improvement at different times. These are family-observed temporal associations, not controlled evidence of efficacy or a recommendation to avoid vaccination.
A November 2025 functional-medicine list recommended numerous phospholipid, lipid, mineral, probiotic, prescription, and compounded products and recorded cephalexin use. A recommendation list does not show that every product was taken or that any produced benefit.
At a 2025 neurology follow-up, the family reports that as-needed guanfacine was suggested for illness-related dysregulation, but it had not been started. Peptides and CBD were being considered, not used as established treatment.
She reportedly underwent anesthesia for MRI and adenoidectomy without an acute procedural complication. Her family nevertheless observed a marked behavioral or regulation flare after an anesthesia exposure and included that response among her recurring state-change concerns. The responsible procedure or agents, exact latency, duration, and recovery course were not fully preserved. This history is important for future procedural planning, but it does not establish an anesthetic allergy, permanent injury, or generalized medication resistance.
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Growth and general health
Her family recalls that weight was near the 10th percentile during infancy. Later appetite and growth have been described as normal, without failure to thrive. No longitudinal growth chart was available, and no endocrine, pubertal, fracture, or bone-health concern was documented in the reviewed materials.
The reviewed materials did not establish chronic cardiac disease, dysautonomia, kidney disease, immune deficiency, mitochondrial disease, chronic inflammatory bowel disease, epilepsy, or a progressive neurodegenerative disorder. In each of those areas, “not established” should not be confused with “fully assessed and permanently excluded.”
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Current supports and practical needs
Formal therapy and school records support continued attention to:
continued occupational, physical, and speech-language therapy matched to current goals;
explicit help with word retrieval, narrative organization, inferencing, perspective taking, pragmatic language, and communicating with less-familiar people;
support for planning, initiation, sequencing, multistep work, and task completion;
visual-motor and handwriting accommodations;
time and reduced competing demand in visually moving or sensory-dense environments.
Additional practical points for the family and treating team to consider include monitoring visual fatigue and changing movement patterns; reducing competing demands during illness or sleep loss; recognizing that off-baseline behavior may reflect sensory, cognitive, or physical strain; supporting skin and nail safety; and documenting the timing and duration of changes around illnesses, medications, supplements, antibiotics, antifungals, and anesthesia.
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The whole person
Her history includes a de novo pathogenic ASH1L frameshift, subtle early motor and feeding differences, a complex language profile, executive-function needs, visual and left-right asymmetry, motor-planning and coordination difficulty, complex movements—including recorded events without an EEG correlate—illness-linked regulation changes, reported earlier sinus, mastoid, and adenoidal findings, unusual laboratory results, and notable family-observed responses to antibiotics and anesthesia.
Those findings are real, but they are not the whole of her.
She is conversational, social, engaged, and increasingly skilled. Her family describes friendships and regular-classroom participation, while formal therapy and school reports document measurable gains. A severe flare does not define her baseline, and a strong performance in one setting does not erase the effort required in another. Understanding her means holding both truths at once: she has meaningful abilities and relationships, and she may require substantial support when language, movement, vision, sensory input, illness, sleep, and executive demands converge.
October 2024
Ferritin 22, vitamin D 34
Not identified as abnormal in the available report