p.Arg1280* — Ages 21–25 — ASH1L case profile | ASH1L.org

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Chapter 03Cardiac history, systemic illness, infection, and hearing

Cardiac history: early shunt, ventricular ectopy, and three ablations

Her cardiac history is a major part of her story. She underwent three cardiac ablations, reported by her mother at approximately ages seven, eight, and ten. The first detailed procedural record is dated 3 December 2010, when she was seven. Procedural records for the other two ablations were not available in the reviewed materials. A separate invasive electrophysiology study on 11 May 2011 was diagnostic only; no ablation was performed during that study. Both the 2021 genetics report and the 2026 exome re-evaluation describe ventricular extrasystoles with repeated ablations.

Early murmur and patent foramen ovale

An incidental murmur was evaluated in July 2007. Echocardiography showed a small left-to-right interatrial shunt considered more consistent with a patent foramen ovale than an atrial septal defect. There was no right-heart enlargement or hemodynamic significance. Later records describe spontaneous closure by February 2010.

Her family remembers that the rhythm problem was first recognized around age six during a school-entry health evaluation. Cardiology records document ventricular extrasystoles - premature ventricular beats or ventricular ectopy - by mid-2009.

First documented ablation and subsequent rhythm findings

Cardiac history: early shunt, ventricular ectopy, and three ablations: First documented ablation and subsequent rhythm findings
Date or period	Cardiac finding or procedure

Three days later	Holter monitoring showed sinus rhythm with 5,222 monomorphic ventricular extrasystoles, approximately 4.3% of beats. There were no couplets or salvos. Mean heart rate was 106/min, minimum 60, and maximum 166.

January 2011	During a systemic-illness admission, Holter monitoring showed a mean heart rate of 113, minimum 77, and maximum 148. At times there were more than 30 ventricular extrasystoles per hour, with occasional bigeminy and no ventricular tachycardia.

March 2011

Holter monitoring captured approximately seven minutes of nocturnal ventricular bigeminy, with monomorphic ectopy and no salvos. Exercise testing reached 50 W over 7.5 minutes and stopped because of generalized exhaustion. Heart rate rose from 130 to 195, but no extrasystoles, ischemic changes, or arrhythmia occurred during exercise or recovery. Everyday activity and sport were not restricted at that time.

March 2011 cardiac MRI	A later cardiology summary states that there was no definite arrhythmogenic right-ventricular dysplasia and mentions a possible post-inflammatory apical change. The scan was performed under anesthesia without a reported complication.

May 2011 invasive EP study

Under propofol, there was no spontaneous ventricular ectopy and none could be induced with orciprenaline or programmed right-ventricular stimulation. AV-node physiology was normal, no accessory pathway was found, and no sustained arrhythmia was induced. Right-ventricular angiography was normal apart from very slight apical hypocontractility. No ablation was performed because there was no inducible target.

May 2011, after the EP study	A 48-hour Holter showed approximately 12,500 monomorphic ventricular extrasystoles, about 10% of QRS complexes, occurring almost exclusively during deep sleep. There was frequent bigeminy or trigeminy and four monomorphic couplets, but no sustained or polymorphic ventricular arrhythmia. Minimum heart rate was 69, mean 118, and maximum 167.

The 2011 systemic illness and broad inpatient evaluation

From mid- to late January 2011, she was hospitalized in pediatric cardiology with fever and cough after a period of pronounced apathy, pallor, fatigue, reduced endurance, night sweats, and substantial weight loss. The history described temperatures up to 40 °C, nocturnal urination as often as three times a night, and approximately 6 kg of weight loss over the preceding year. She was very slender: 20 kg at approximately the 5th percentile and 137 cm at approximately the 96th percentile. Examination noted small mobile lymph nodes near the jaw angles and oral aphthae or reddened lips.

Chest radiography and abdominal ultrasound were unremarkable. Blood cultures showed no growth. Testing was negative or unrevealing for adenovirus DNA, HHV-6, HIV, parvovirus B19, HSV, CMV, EBV, respiratory viruses including influenza, tuberculosis, and celiac disease. A blood smear showed reactive viral-type changes without blasts. The thyroid evaluation was unrevealing. Repeated cultures and echocardiography did not support endocarditis.

Echocardiography showed a hyperdynamic left ventricle, a normal slender right ventricle, no endocarditic lesion, and slightly unusual septal movement near the right-ventricular outflow or ablation region. Right-ventricular dysplasia could not be excluded by echocardiography alone, which led to the later cardiac MRI; the subsequent summary did not find definite arrhythmogenic right-ventricular dysplasia.

January testing showed low serum iron with transferrin saturation of 5%, low vitamin D at 19.1 against the displayed 30-100 reference interval, and mildly low uric acid. Ferritin, HbA1c, CK, troponin I, NT-proBNP, TSH, creatinine, white-cell counts, sodium, potassium, calcium, phosphate, magnesium, urea, transferrin, and procalcitonin were within or returned toward the local laboratory ranges. CRP decreased during the admission. Additional recorded results included IgG 9.66, IgA 1.17, IgM 1.31, IgE 26.20, complement C3 1.07, complement C4 0.25, CK 89 and 100, vitamin B12 1,054, procalcitonin 0.09, and ESR 10. Folate was above the displayed 3.1-17.5 interval at >20. None of these findings was identified in the discharge summary as the cause of the illness.

No single cause was identified. The fever stopped, and the night sweats, exhaustion, and other constitutional symptoms resolved during the final inpatient week. She was discharged clinically well.

In March 2011, while rapid fatigue and night sweats were still being followed, laboratory testing showed WBC 5.81 G/L, hemoglobin 12.4 g/dL, platelets 251,000/µL, sodium 140 mmol/L, potassium 4.19 mmol/L, calcium 2.22 mmol/L, phosphate 1.64 mmol/L, magnesium 0.93 mmol/L, creatinine 0.63 mg/dL, troponin I <0.02 ng/mL, NT-proBNP 25 pg/mL, and soluble IL-2 receptor 371 U/mL. Borrelia IgG and IgM were negative at that time.

Childhood illness, vaccination chronology, and recurrent infections

Ear and respiratory illness had already begun before the severe event in November 2006. In September 2006 there were bilateral middle-ear effusions and upper-airway symptoms; in early November she had bronchitis and received antibiotics.

The vaccination booklet documents Pneumovax 23 and Varilrix in late November 2006. Her mother reports that fever and pronounced right-leg swelling began within approximately 30 minutes, followed by fever to approximately 41 °C, uncontrollable vomiting, inability to walk, and a 14-day hospitalization. Her family remembers her as unusually withdrawn with a blank facial expression afterward.

The family initially understood her developmental delay through the acute event and the prolonged illness that followed. That chronology is important, but timing alone does not establish that either vaccine caused the acute illness or her later developmental, infectious, or cardiac findings. Later routine boosters and COVID-19 vaccinations are recorded, and vaccination continued. Her mother reports that vaccine-antibody titers have not been measured in her.

The months after the acute event were medically difficult. The family chronology records recurrent bronchitis, pneumonia-like illness, pharyngitis or scarlet-fever-like illness with high temperatures, additional antibiotics, weakness, and weight loss. Over approximately 18 months, her family reports repeated otitis, sinusitis, bronchitis, pneumonia, pneumococci detected in middle-ear material, and multiple antibiotic courses - six by family recollection - before pneumococci were no longer found.

Her family remembers four ENT procedures: two adenoid or "polyp" procedures and two sets of ventilation tubes. The 2012 clinical history records recurrent otitis, adenoid removal, paracentesis, and ventilation tubes at approximately age four. Speech and communication improved after the ENT disease was treated.

The family chronology also records a tick bite in May 2007, lower-leg and foot pain about two weeks later, peeling skin on the hands in early July, a reportedly positive Borrelia blood test, and antibiotic treatment from approximately July through September. Her family says she was unable to attend kindergarten from approximately July through December 2007 during this prolonged illness period. Formal Borrelia IgG and IgM testing in 2011 was negative. The later result does not establish the cause of the 2007 episode.