English

His words: “I started to feel unwell in the summer of 2015 (13 years old). Moments when I felt a little more tired started to appear. I could do any kind of sport back then. I went to the gym for 3 months, I rode my bike a lot, I played basketball … And the next summer, the same, and I didn’t feel any other problem. Those moments when I got tired, however, became more and more frequent. In the middle of the 9th grade (2017), every day, around 1 PM, I ended up feeling quite tired. I started sleeping when I came home from school. After sleeping I felt good again. During the morning I felt more tired than in the evening. At the end of summer 2017, pain began to appear in the upper right part of the abdomen and a sensation of sensitivity in that area; it hurt even at light pressure, and at physical exercises. When I stopped going to the gym, the pain eased, but the sensitivity remained. I remember that in the 10th grade, when I was just 16 years old (February 2018) I started to feel really sick. Fatigue had turned into something much stronger, an abnormal sensation. I know, because I’ve been healthy and tired before. I have felt normal fatigue. Even when it was strong, it didn’t feel this way. This is a malaise, unnatural, that feels like it shouldn’t be there, completely different from the fatigue you feel if you don’t get enough sleep or if you demand too much of your body. In the first part of the day, I felt worse. In the evening, my condition was still bearable, and because I could not accept that I was losing my ability to live a normal life, I went to the gym again the following summer. But, after effort, I was even more tired, I didn’t feel well at all. At 17 years old (2019), I already had problems in the simple act of going for a walk with my friends, which was not even daily. I started to feel ill in the evenings as well. The mornings had long become a daily ordeal. In the 12th grade, I often had to leave school in the last hours because I had to sleep, I felt too unwell. I was „lucky” with the pandemic, which allowed me not to leave the house too long, because I honestly couldn’t. My body is failing me. I won’t last like this much longer. I can feel it.

Male patient, now 20 years old, began to experience moments of undue fatigue 7 years ago (in the summer of 2015. He was 13.5 years old). Over the next 2 years, the fatigue appeared more and more often until it became daily, then he started stretching for more and more hours, until it became a continuous state, in 2017. From 2017 (at the age of 15) he started having mild discomfort and pain in his right abdomen after exercise (he played basketball, rode his bike, went to the gym). Since 2018, his condition deteriorated faster, fatigue took hold of his life, and various other symptoms began to appear.

Summarily

Moments (hours) of inexplicable fatigue began 7 years ago. No acute onset. Summer 2015. He: 13 years old. Over the next 2 years, the length, intensity, and frequency of fatigue hourly intervals gradually increased until they merged, becoming a continuous state, which only continued to intensify. The malaise was always stronger in the first part of the day ● Hyperechoic liver already at the age of 13 (2015) ● Degenerative bone changes ● At exercise (at the gym) began to appear pain in the upper right abdomen, place fixed (photo) ● From 2018 (3 years after the appearance of the first states of fatigue), his heart started to show that it is suffering. Hyperkinetic syndrome, mitral valve: sheets with micronodular thickening, regurgitation („light”) on all valves ● Sport / physical exertion began to intensify his malaise, forcing him to reduce the intensity of physical stress. Recovery, after exercise, was more and more difficult ● His general condition was continuously deteriorating, with increasing speed. Fatigue was getting stronger ● Since 2019, his heartbeat is very strong, all the time (day and night), since then (3 years already!) ● HTA. Ex: 150/70, 90-100 BPM. ● 2019: Straight Branch Block (new) ● 2019: CK (creatine kinase) 7 times higher, 1 week after exertion. Muscle fever, with burning sensation, 2-3 weeks. In the absence of physical effort, CK is normal! ● 2020: ischemia test (arm, 5 min.): 200% increase in serum lactate. Almost instantaneous acidosis ● 2020 (18 years): Hypertrophic heart, tricuspid insufficiency „1-2”, IM „1” ● Liver and spleen found at the costal rim, from 2019 ● Sensation of dry throat and mouth, appear and install from 2019. They are very strong. Frequency: 1-2 days. It was not diabetes insipidus (desmopressin test). ● Constant since 2015: high serum bilirubin (total, direct), low serum creatinine, low total cholesterol and HDL, low reticulocytes, fraction of immature reticulocytes: low, MCHC, MCH, MCV, MPV: slightly lower from the first analysis (at 5 years) Low hemoglobin or low limit ● Low cortisol / low in the morning, inhomogeneous pituitary gland (MRI). ● Inconsistent: renin: triple in 2019, 17 ketosteroids: double in 2019 and triple in 2020 and many more (table 15 pages) ● Reactive lymph nodes, discovered in 2019 (we don’t know when they date): axillary, mediastinal, abdominal, pelvic ● Submandibular, jugulo-carotid, occipital, parotid adenomegaly ● Nodular lymphoid hyperplasia (ileum), hyperplastic lymphoid follicles (colon), discovered in 2020 (we don’t know when they are) ● Chronic hepatic and intestinal lympho-plasma cell infiltrate ● Nasal corneal mucosa: almost total obstruction in 2022 ● HOMA (insulin resistance) index in diabetics ● Low amylase ● 03.2022: Fluid accumulation in the upper aortic pericardial recess.

DEGENERATIVE CHANGES in the scanned BONES (abdomen-pelvis) have been mentioned since 2020, but we cannot know when they started and if it happens to all the bones of the body.

Ionic calcium has often exceeded the range of normal values, but with very little. Low vitamin D, even with a supplement, does not reach normal. Supplement 2000 IU / day. He only took 4,000 IU a few days, he felt worse and the pain in the right upper part of the abdomen intensified. Erythropoietin was low in 2018. Reticulocytes are low in many tests, and the fraction of immature reticulocytes is almost always low!

UPDATE: 05.2022: Examination of the right inguinal ganglion, with preserved architecture. Germination centers reagents: rare. Areas with nodular and diffuse paracortical hyperplasia. Histiocytosis sinusala. Histopathological examination: HE coloring -microscopy: CD20 is positive in reactive follicular B structures; CD30 is positive in small activated lymphocytes, isolated; CD3 is positive in very common small T lymphocytes paracortical reagents. Ki67 proliferation index very high in germination centers reagents. Paracortical: ~ 5%

More detailed description, containing the history before 2015:

Male patient, age 20, without particularities at birth (3,200 kg, 50 cm), normal physical and mental development during childhood and adolescence. Superior intelligence, athletic constitution: 186 cm, 78 kg (when he could still exercise). 2020-2021 ranges between 92-94 kg.

I add these events, although they may or may not have anything to do with the symptoms that began to show in 2015 (he was born in 2002). From the age of 6 months to 7 years, there was a loss of consciousness, which occurred 4 times, with the cessation of breathing (I don’t know if it was also cardiac arrest, because I proceeded instantly to cardiac massage and mouth-to-mouth breathing, I didn’t waste a second. All these episodes occurred in moments of relaxation and from a horizontal position. The body and limbs initially became stiff, breathing seemed absent, the eyes remained fixed, open, then the body became soft. He no longer responded to stimuli. I noticed him immediately every time, because I was with him all his childhood. The last time, at the age of 7, I resuscitated him the hardest: in 2 minutes, maybe 3. I don’t know if he fainted, if he had recovered on his own, although I don’t think so, because he didn’t seem to be breathing anymore. An ambulance was called each time; when he arrived, he was already aware again. He was confused, but his body was working. An electroencephalogram found nothing. There has never been a further investigation in this direction.

At age 5 (first blood test): Hemoglobin, MCHC, MCH, MCV all (slightly) low. To date, these, together with the average platelet volume (MPV), appear either at a minimum or slightly lower than normal. Flat and leukocyte epithelia, calcium oxalate and amorphous salts are present in his urine.

Stings and pain in the heart area, since early childhood. Distribution: diffuse. Time: 2-3 min. They did not radiate to the neck, arm or back.

From the age of 6 to 12, at least once a year, he arrived at the emergency room with acute pain in his right abdomen and headache.Suspected acute appendicitis each time, unconfirmed. In 2013 (11 years), this happened 3 times! No nausea, vomiting, diarrhea, dizziness. No fever.

At 10 years old (2012): right heel crack from a blow that was not very strong, with the heel, in cement. Dexamethasone, injected topically, 5 doses. Suspicion of bilateral „pes cavus”, was noted on the x-ray bulletin.

At the indication of the orthopedic doctor, in order to support physical activity that does not involve the use of the affected heel, he went to the gym from 11 to 16 years old, in the summers. He also rode his bike a lot. He played basketball..

12-16 years: some dislocations in the ankles and a metatarsal fracture (wrong lateral movement + metal muzzle boots).

In the summer of 2015 (age 13 and a half), he begins to feel these strange states of fatigue. Initially they lasted a few hours and appeared every few days. The interval decreases over the course of 2 years, until the fatigue reaches a continuous state, which then only worsens and complicates.

The first abdominal ultrasound reveals an already hyperechoic liver.

The period in which the fatigue started to appear, was NOT marked by any ACUTE event. Only a few blood tests are done: eosinophils appear increased in percentage (they have increased and remained almost constantly increased for 2-3 years). The few tests did not identify common parasites. Low serum creatinine, from the first tests onwards. Urine: calcium oxalate, flat epithelial cells, red blood cells, leukocytes (exactly as in the tests from the age of 5 years).

No contact with farm animals. We live in the city. We have not traveled outside Romania yet. Rare contact with animals occasionally rescued by me. No contact with toxins. No excess food. We have a balanced diet. I don’t smoke, I have no vices. He was just a normal kid with a good life. And he did sports.

Due to the fact that the only symptom, although overwhelming, was that fatigue that he did not know how to describe properly, from all the consultations in 2015-2018, we were sent home without any answer, without indications.

 Since september 2019 (final high school year), he only lasted (physically) halfway through the program of a school day. He was allowed by the teachers to go home when he felt worse. As of 2019, sleep could do little to improve his condition. In 2020, when the pandemic started, and he didn’t have to go to high school anymore, the lack of effort made him feel a little better for a while. After a few months, however, the condition worsened further.

GASTRIC-LIVER disorders:

Between the ages of 6 and 11 (2008-2013), yearly, acute pain in the right abdomen + headache, suspected of acute appendicitis, diagnosis denied every time (in 2013 even 3 times). In almost all ultrasounds, even from the age of 13, the increased echogenicity of the liver was noticed.Direct bilirubin 25-50% above the limit, and has remained outside the reference range, since the first dates when it was taken, in 2017 (15 years).

LIVER AND SPLINE AT THE COASTAL RIM many times, from 2019; in 2021: at all exams.

Pain in the upper right abdomen has always been associated with fatigue and feeling sick.

– Describes a permanent feeling of „vulnerability” in that area.

The area is extremely sensitive. He protects it just like a BURN.

– It hurts when pressed, even lightly, and when fatigue reaches a threshold. From 2021 the pain appears daily, without physical effort. Fatigue now oscillates only at high degrees.

The painful area has expanded in the last 2 years, to the right, slightly down.

FIBROMAX (serum analysis, November 2019 (almost 18 years), and repeated after 8 months (in July 2020), indicates: LIVER FIBROSIS grade 1-2 (0.33 out of 1), HEPATIC STEATOSIS (0.22 out of 1), Necrotico-Inflammatory Activity ( 0.18 out of 1) and Inflammation from Metabolic Disorders „NashTest” (0.25 out of 1).

– Fibroscan, May 2021: AVERAGE HEPATIC RIGIDITY: 4.1 KPa;

Hepatic Biopsy from December 2021, does NOT describe fibrosis! Blades are still available. I can take them.

“Multiple small fragments of liver tissue with minimal chronic lympho-plasma inflammatory infiltrate at the level of the intercepted portal spaces; Isolated microvesicular steatosis ”

– Endoscopy: „Terminal ileum mucosa, with NODULAR LYMPHOID HYPERPLASIA. Colonic mucosa: edema „lamina propria” and „HYPERPLASTIC LYMPHOIC FOLICOS PRESENT IN ALL FRAGMENTS EXAMINED” (2021);

PANCREAS: HYPERECOGENE ECOSTRUCTURE (May 2021). Amylase dropped sharply in 2019 and has remained so.

– 2018: antral gastritis and duodenitis: „lymph-plasma infiltrate, congestion, edema” (endoscopy).

– Gallbladder: cudate and septate. Sludge present (2019). Dense bile content (2020).

– 2020 MRI, 2021 CT: Rectum and sigmoid colon: suboptimal distension, „partially undistinguished intestinal loops”

2021: INSULIN RESISTANCE (HOMA index) discovered. Glucose intolerance appears (intermittent) since Dec.2021.

Cardiology:

Stings and pain in the heart area: they have been present since an early age. Sometimes very powerful.

August 2018: first visit to cardiology. EKG: BRADICARDIA: 50 BPM. Normal NT-proBNP. Eco-cord:

▪HYPERKINETIC SYNDROME; • Mitral valve „Sheets with micronodular thickening at the edges”

▪Tricuspid valve: mild regurgitation • Pulmonary valve: mild multijet regurgitation;

▪ E / e ’side Mi ring: 3.76 (V max: 0.16); • E / e ring Mi septal: 7.66 (V max: 0.14);

From 2019 THE HEART STARTED BEATING VERY STRONGLY (not fast).And this aspect has become permanent.

HE STRONGLY FEELS HIS PULSE, ALL OVER HIS BODY, ALL THE TIME. When he feels worse, he also feels his heart beating harder. Sometimes, during sleep, it can be seen how the whole body is moved by the force of the pulse.

He feels like there isn’t enough air in the room almost every day. He had cold sweats for a period of 3 days, in 2019. A few months later, a RIGHT BRANCH BLOCK (NEW) wasdiscovered.

SISTOLIC BLOW grade 2 parasternal left (12.2019);

➢ slightly THICKENED MITRAL VALVE (Color Eco Doppler, 01.2020);

Cardiac Holter ECG/24 hours (04.2020), „Dangers Analyse„: 7 out of 10 indicators, have values outside the ranges:

At 8 PM, a few minutes of physical effort (moderate intensity): 181 BPM!

February 2021:

BRANCH BLOCK (minor BRD),

VENTRICULAR HYPERTROPHY

TRICUSPIDIAN INSUFFICIENCY I-II,

MITRAL INSUFFICIENCY I,

Apical PL HYPOKINESIS

LV undilated with mild septal HVS;

HTA borderline:

Values measured in moments of rest: 131/80 with 90 BPM, 152/77 with 90 BPM, 135/84 with 98 BPM, 151/78 with 64 BPM, 139/85 with 79 BPM, 131/95 with 95 BPM.

March 2021: 156/92 and 109 BPM, after a 10 minute walk, normal walking (not alert) and 5 minute rest.

Now, another 1 year has passed, without any help (treatment..?).

  • CT 03.2021: Fluid accumulation in the upper aortic pericardial recess!

Endocrinologicallly briefly investigated, only from 2019 (17 and a half years already)

SERIC CORTIZOL was low in 2019. Then around the minimum, determined in optimal conditions;

NEOMOGENEOUS HYPOPHYSIS It was said to be normal (?), Native and postcontrast, weak MRI (0.4 T), 2019

17 KETOSTEROIDS: increased! x 3 in 01.2020. Double in 2019. He had a normal weight. BMI is now slightly higher.

– ACTH normal, FT4 minimum. Diffuse „non-toxic” goiter (2020). The thyroid area looks slightly bulging.

– Dec 2019: RENIN, normal. After only half a year, in July 2020, it exceeds 3 times the maximum normal: 83.58 (int 2-27). Aldosterone, however, in the normal range: 113 (24-403). Renin is normal again after a year, on 08.2021, and aldosterone has not been tested since.

– 2019-2020: Lutropin (LH) increased, Progesterone VERY low, 17 OH-progesterone increased, IGF -i increased, prolactin increased. Free testosterone: normal, total testosterone low 2019-2020, in 2021: normal.

I don’t know if the following 3 issues have an endocrinological cause, but they could, so I put them here:

– In the first part of the day, his condition is worse; he feels more of that strange, bad fatigue. For a while, this aspect has been barely noticeable, because he feels very ill all the time. There is also a minimum of malaise: somewhere at 11-12 at night. This is on days when no physical effort is involved.

– Problems with temperature regulation. For 4 years already (2018). As it gets a little cold, he is suddenly cold. He seems to be unable to produce the necessary body heat. On days when he feels more of that malaise, he is even colder than usual. His hands are often very cold. His body doesn’t seem to emit any heat at all.

– Vitamin D was found to be deficient at 17 years of age. The analysis had never been done before, so it may have been deficient for 17 years.

Someone should find out if this deficiency is due to liver damage or if there is another cause. And what effects it had.

Physical effort increases his malaise (from 2018)

In the summer of 2018, he experienced this: after only half an hour of exercise at the gym, he suddenly felt very bad, and for 2 hours he felt as if every cell was vibrating. A general condition of severe malaise. Also in 2018, after a few days in which he really wanted to go cycling with his friends, he got a state of fatigue that seemed to never pass! For 3 weeks, neither night nor day sleep mattered.

In 2019, just by chance, CK was found 7 times above the maximum limit: 2829 (int: 55-370). 1 week before, he had done a series of 5 consecutive days, when, although it was difficult for him, he did exercises at the gym for half an hour/day. He then had amuscle fever with a burning sensation, which lasted for more than 2 weeks. In the absence of physical effort, CK is normal!

He showed neither muscle weakness nor inability to sustain any effort. It was just that he felt really bad after, like a man with the flu, for example, if he was forced to do sports or physical work.

In August 2020, an electromyography was performed with and without an intramuscular needle. Values were considered normal. EMG analysis and report, attached.

In February 2021, the left upper limb ischemia test to monitor serum lactate. An increase of > 200% in post-exercise lactate was found, compared to the initial resting value (sample 1: 1,3 mmol/l; sample 2: 4,3; sample 3: 1,5).

From what I understand, the increase in serum lactate would exclude McArdle’s, in which it should have been low (is that correct?).

Symptoms of which I don’t know what category they belong to:

DRY THROAT and MOUTH sensation, every day. Since 2019. It is not remedied if he drinks water. Suspicion of diabetes insipidus was raised, but under the influence of desmopressin, he concentrated his urine perfectly. Insulin resistance was only discovered in 2021 (HOMA index – first done in 01.2021). Blood glucose had normal values throughout the years. Insulin crashes from 20 to 9 in 2 weeks (January 25-February 9, 2021). It has not been analyzed for 1 year. The feeling of dry mouth and throat seems to be related to the need for sweets in the diet, because consuming them is the only way it diminishes.

The feeling of „sand in the eyes” appeared daily in 2019-2020. In 2021, after hepatoprotectors: thistle and silymarin, this sensation reduced its appearance to monthly. However, eye pressure occurs daily for about 3 years. The eyes have permanently visible blood vessels. He was examined in ophthalmology. Apart from myopia, and a small difference in the amount of fluid produced by the tear glands in the right eye compared to those in the left eye, there seems to be no eye problems.

➢ A problem with a major impact, both on the spine and the existing abdominal discomfort: he can only fall asleep on his stomach. In any other position he tries, his malaise continues to increase until he can no longer bear it and he positions himself back on his stomach. What could be the cause of this symptom? I mention that it has been present for several years already!

➢ A daily problem, very disturbing and deeply worrying: NOSE CONGESTION, permanently present, bilaterally, regardless of the season, has worsened in recent months, and now he can only breathe with the help of Olinth. He administers it 5-6 times a day. Without it, he wouldn’t breathe at all!

Latest informations (03-04.2022):

  • Microscopic examination of the inguinal ganglion indicates chronic reactive lymphadenitis (nonspecific).
  • Urinary Creatinine 200 (int: 10-50) DIABETES??
  • Pulmonary RG: “BILATERAL BASAL INTERSTITIAL CHANGES; slight thickening of the horizontal slit.

He has no treatment for the discovered ailments.

Nobody monitors his condition. He takes only hepatoprotives (Liv 52), and Vit D, with breaks.

Conditions or illnesses verified:

Epstein-Barr Virus, found positive, but already old in 2018: IgG 44.9 (<20), IgM: <10 (<20), 2019: IgM <0.1 U/ml (<20), 2022: VCA IgM: <10 (<20), VCA IgG: 44.8 (<20), Anti-EBNA: >600 (int 10-50) 03.2022!

Hepatitis A, B, C, HIV: negative (repeated tests), Autoimmune hepatitis: negative (2 tests);

Negative results, but from tests performed only once: Borellia, Cytomegalovirus, Toxocara canis, Toxoplasma gondii, Aspergillus Fumigatus, Echinococcus Granulosus.

Negative allergens („full” panel), CEA: 0.679 (int: less than 3, for non-smokers): 2018; CA 19-9: 2.88 (negative <33): 2018; Serum microglobulin beta 2: 1.41 (int: 1.09-2.53): 2018; Autoimmune serology negative: Dec. 2019: ANA (extended) negative: 0.20 (int <1), SS-A 52 (Ro 52), SS-A 60 (Ro 60), SS-B (La), RNP/Sm, RNP -70 , RNP-A, RNP-C, Sm-BB’, Sm-D, Sm-E, Sm-F, Sm-G, Sci-70, Jo-1, dsDNA, ssDNS, polynucleosomes , mononucleosomes, histone complex, histones H1, H2A, H2B, H3, H4, PM-Sci-100, centromere B; Anti-tissue transglutaminase antibody: negative IgA 0.1 (<10), IgG 1.1 (<10), Anti-ASMA antibody 4.84 (<20); Double-stranded ANTI-DNA antibody R <10 (negative) 09.2018 and 02.2021. Antinuclear antibodies: negative (2021); Total rheumatoid factor (serum); negative: <10 (int <10): May 23, 2018, repeated 2021; Direct Coombs test: negative, 2019; Cryoglobulins: absent (2019); Urinary hemosiderin (in 24h urine): absent (2019); Helicobacter Pylori antigen – Positive (2+) on biopsy: 05.2021. Treatment carried out: 7 days. AFP (Alpha-fetoprotein): 1.12 (int: <7) 2020; ATPO (Anti Thyroperoxidase): 0.72, int<10; ATG (anti-thyroglobulin antibody) R: <1, int: <4; Quantiferon test. The presence of interferon-gamma specific for M. tuberculosis infection was not detected. Suspected CARNITINE deficiency (2021): negative (blood and urine carnitine assays show normal production). Pompe disease: negative (February 2021); Fabry disease: negative (Alpha-galactosidase in the blood: 46.6 nmol/mg (int: 14-72.6)). 08.2021; Tangier disease: negative (alipoprotein A1 is in range) 2021; Wilson’s disease (liver biopsy) negative (December 2021). McArdle – negative??? (serum lactate increases with exercise).

Genetics: The panel for rhabdomyolysis and the panel for lysosomal and mitochondrial disorders in nuclear DNA, together reported 10 changes: 9 heterozygous, 1 homozygous (result annexed). Analysis for suspected mitochondrial cytopathy, performed on mitochondrial DNA, gave a negative result.

Awaiting your response, please accept, Ladies and Gentlemen, my best regards!

Email us at verde.gri@yahoo.com