Age: 30.0
Sex: M
Vaccine: COVID19
Symptoms: Cardiopulmonary exercise test, Cytogenetic analysis, Electrocardiogram, Exercise test, Glycogen storage disorder
Clinical narrative: documented lactic acidosis after walk/exercise; suspicion for a glycogen storage disorder or a mitochondrial myopathy; suspicion for a glycogen storage disorder or a mitochondrial myopathy/mitochondrial dysfunction; This is a spontaneous report received from contactable reporter(s) (Consumer or other non HCP and Other HCP).  A 30-year-old male patient received BNT162b2 (BNT162B2), on 22Feb2021 as dose 2, single (Lot number: EN6200) at the age of 30 years for covid-19 immunisation. The patient's relevant medical history included: "Hereditary Alpha Tryptasemia" (unspecified if ongoing). Concomitant medication(s) included: METOPROLOL (ongoing); CLONIDINE (ongoing); ALLEGRA [FEXOFENADINE HYDROCHLORIDE] (ongoing); GABAPENTIN (ongoing); PREDNISOLONE (ongoing); VYVANSE (ongoing); XARELTO (ongoing); LANSOPRAZOLE (ongoing). Vaccination history included: BNT162b2 (Dose 1, single, Lot : EL9262), administration date: 01Feb2021, when the patient was 30-year-old, for Covid-19 Immunization. The following information was reported: LACTIC ACIDOSIS (medically significant) with onset Feb2021, outcome "recovering", described as "documented lactic acidosis after walk/exercise"; GLYCOGEN STORAGE DISORDER (medically significant) with onset Feb2021, outcome "recovering", described as "suspicion for a glycogen storage disorder or a mitochondrial myopathy"; MITOCHONDRIAL MYOPATHY (medically significant) with onset Feb2021, outcome "recovering", described as "suspicion for a glycogen storage disorder or a mitochondrial myopathy/mitochondrial dysfunction". The event "documented lactic acidosis after walk/exercise" required physician office visit and emergency room visit. The patient underwent the following laboratory tests and procedures: Blood creatine phosphokinase: (unspecified date) normal, notes: no evidence of vascular claudication; Blood gases: (unspecified date) 7.40/42/118/26, notes: lactate of 1.8mmol/L/Peak ABG and lactate were as follows: 7.22/29/127/12 and lactate of 20.0 mmol/L; Blood lactic acid: (unspecified date) 20.0 mmol/L; Blood pressure measurement: (unspecified date) 131/83, notes: He was mildly tachycardic in the ED with HRS of 94 and 103 with normal blood pressure except for one reading of 131/83; (unspecified date) 140/88; (unspecified date) normal; (unspecified date) 147/62; Cardiac stress test: (unspecified date) HR at baseline was 87, notes: HR at baseline was 87 with a blood pressure of 140/88 and pulse ox of 97%. HR at peak exercise was 189 with blood pressure of 147/62 and pulse ox of 94%; (unspecified date) 94; (unspecified date) 103; Cardiopulmonary exercise test: (unspecified date) severe lactic acidosis after a slight exercise, notes: got sustained palpitations and strong fatigue; Cytogenetic analysis: (unspecified date) did not show any mitochondrial mutations; Electrocardiogram: (unspecified date) Unknown Results; (unspecified date) normal cardiac function, notes: by recent echocardiogram; Exercise test: (14Apr2021) During the exercise, he reports that he felt well, notes: without any issues. However, after approx. 10 minutes of exercise, he stopped the test due to fatigue and then 10 minutes after that, he started to feel unwell. His heart rate was in the 130s to 140s; Heart rate: (unspecified date) 130s to 140s; (unspecified date) 87, notes: HR at peak exercise was 189; Oxygen saturation: (unspecified date) could be in 80-90s without him realizing; (unspecified date) 97 %; (unspecified date) 94  %, notes: Respiratory quotient at baseline is 0.81 and at peak is 1.24. Therapeutic measures were taken as a result of lactic acidosis, glycogen storage disorder, mitochondrial myopathy. Clinical course. In 2020, was regularly exercising and running 5-10 miles every day. However, shortly after 2nd Covid vaccination he stopped being able to walk or exercise. A CPET test at medical centre showed that he had severe lactic acidosis after a slight exercise. Thorough genetic testing did not show any mitochondrial mutations, so it's still unclear why the patient had severe lactic acidosis after slight exercise. Patient exercises every day for months now and it was unclear how he can exercise and feel great sometimes but then walk or nap and feel strong fatigue similar to after the lactic acidosis case. Turns out during a walk, similar to central apnea episodes, patient doesn't adequately breath and his Oxygen could be in 80-90s without him realizing. When the oxygen desaturation persists for a long period of time when the patient walks, he then starts to feel strong malaise and fatigue. On 03Sep2021, vaccinated with COVID-19 Moderna Vaccine, mRNA, PF (Lot #: 939901). Timeline View of Symptoms: Feb2021 onwards: No more can walk for more than 5-10 minutes without strong fatigue and palpitations afterwards. Happened after Covid vaccine. Before was running 5-10 miles per day. After a Cardio-Pulmonary Test (CPET) at medical center got sustained palpitations and strong fatigue and was sent to the ER (emergency room) by the doctors, where the usual ECG tests did not reveal anything. Later studies showed that he had severe lactic acidosis after the test, which was probably either autonomic or mitochondrial dysfunction. Intermittent Central Apneas: since patient's symptoms are intermittent and sleep studies typically must be scheduled in advance, it was not possible to arrange a formal sleep study. However, the patient bought and calibrated a few oxygen meters and a blood pressure device to record some of the episodes. In addition, patient's wife, who also works in the medical field, recorded on video a few of the central apnea episodes. Patient seems to have apnoeic episodes during some days and nights. History of Present Illness: A 31-year-old male with heredity alpha tryptasemia, small fiber neuropathy, POTS (Postural orthostatic tachycardia syndrome), left-sided muscle and joint pain; malaise, exercise intolerance, autonomic dysfunction and GI symptoms who was referred to Metabolism clinic after he was found to have severe lactic acidosis during an exercise tolerance test. (withheld) was referred for an exercise tolerance test as he has had exercise intolerance since Feb2021. (This exercise tolerance is a recent development in the context of (withheld) developing many new symptoms since 2017. Currently, he was limited to 10 minutes of exercise or increased activity before needing to rest. Prior to this, he was able to run 5 to 10 miles a day and was very active. (withheld) underwent an exercise stress test on 14Apr2021 at (withheld) Medical Centre. During the exercise, he reports that he felt well without any issues. However, after approx. 10 minutes of exercise, he stopped the test due to fatigue and then 10 minutes after that, he started to feel unwell. His heart rate was in the 130s to 140s. He was then transported from the exercise test location as a rapid response. He was mildly tachycardic in the (withheld) with HRS of 94 and 103 with normal blood pressure except for one reading of 131/83. His symptoms self-resolved and he was discharged. During the exercise, he reports that he felt well without any issues. However, after approx. 10 minutes of exercise, he stopped the test due to fatigue and then 10 minutes after that, he started to feel unwell. His heart rate was in the 130s to 140s. He was then transported from the exercise test location to the ED as a rapid response He was mildly tachycardic in the ED with HRS of 94 and 103 with normal blood pressure except for one reading of 131/83. His symptoms self-resolved and he was discharged from the ED. Review of the documentation of the exercise stress test from medical Center shows that HR at baseline was 87 with a blood pressure of 140/88 and pulse ox of 97%. HR at peak exercise was 189 with blood pressure of 147/62 and pulse ox of 94%. (Respiratory quotient at baseline is 0.81 and at peak is 1.24). Of great concern was the finding of extreme lactic acidosis with exercise. Baseline ABG and lactate were as follows: 7.40/42/118/26 and lactate of 1.8mmol/L. Peak ABG and lactate were as follows: 7.22/29/127/12 and lactate of 20.0 mmol/L. The report states that has a normal exercise capacity but he has "an early AT (Anaerobic Threshold) and profound lactic acidosis. "During strenuous exercise, adenosine triphosphate synthesis depends, in part on the 02-independent conversion of pyruvate to lactate, the onset of which has been referred to as the anaerobic threshold (AT). The AT was often used in clinical practice as a key measure of overall fitness and cardiovascular function. Although anaerobic cellular metabolism affords continued functional activity during strenuous exercises, elevated levels of lactate quickly exceed endogenous buffering capacity, and minute ventilation (V) must be increased to offset elevated circulating levels of CO2 that are generated through the buffering of lactate by bicarbonate. Eventually, however, lactate concentration exceeds both buffering and ventilatory capacity, resulting in a drop in blood and muscle pH (ie, lactic acidosis) and, ultimately, cessation of physical activity. Thus, an abnormally low AT is generally associated with disorders of 02 transport to, or subsequent uptake by, muscle mitochondrion." Assessment/Plan. Patient was a male with hereditary alpha tryptasemia, postural orthostatic tachycardia syndrome, small fiber neuropathy, left-sided muscle and joint pain; malaise, exercise intolerance, autonomic dysfunction and GI symptoms who was referred to Metabolism clinic after he was found to have severe lactic acidosis during an exercise tolerance test. The findings of a lactate of 20mmol/L after 10 minutes of aerobic exercise is concerning. In an individual with normal cardiac function by recent echocardiogram, a normal CK level and no evidence of vascular claudication, this raises the suspicion for a glycogen storage disorder or a mitochondrial myopathy. has had proband-only genomic sequencing with mitochondrial DNA sequencing which was non-diagnostic However, proband only analysis has diagnostic limitations and after discussion with the genetic counselling team at where the genome sequencing was performed the genomic sequencing analysis did not closely evaluate nuclear genes associated with mitochondrial dysfunction. Thus, they recommended a reanalysis with a focus on the phenotypic findings of lactic acidosis, exercise intolerance, and possible mitochondrial dysfunction. It is also possible that has a mitochondrial deletion or mitochondrial depletion leading to severe mitochondrial dysfunction specifically localized to muscle tissue and not present in the blood. Thus, the work-up for these new findings of exercise intolerance, and severe lactic acidosis during exercise is not complete and requires further evaluation to determine the etiology. The plan was as follows: Obtain reanalysis of genome sequencing at information. Repeat/new laboratory investigations: free and total carnitine levels, plasma acylcarnitine profile, plasma amino acids, urine organic acids, serum fgf21 and serum gdf15 levels with new phenotype, consider thymidine phosphorylase enzyme activity and plasma concentrations of thymidine and deoxyuridine. If the above investigations do not yield additional diagnostic information, a muscle biopsy will be needed. This muscle biopsy is needed for histopathology and respiratory chain enzymology. Asked to return to Metabolism clinic in 6 months or sooner if needed. Patient usually followed an active lifestyle and at a baseline (2019, 2020) typically had 8-10k steps. After developing an autonomic dysfunction, small fiber neuropathy and POTS (Postural orthostatic tachycardia syndrome) around Apr2021, his walking capacity had severely declined. The decline continued from "4k steps in Apr2021 to "3k steps in Jan2022. So, his situation was considerably worse from the baseline and was worsening for many months by the time of starting IVIG infusions slightly before Jan2022. After starting the IVIG infusions, the patient started improving his ability to walk and although not at the baseline of 8-10k steps yet, was able to improve it from "3k steps to "6k steps within 4 months. Whereas prior to that, the patient was deteriorating in terms of walking ability for 10 months.