Long Term Follow-Up of Polish Patients with Isovaleric Aciduria. Clinical and Molecular Delineation of Isovaleric Aciduria
Abstract
:1. Introduction
2. Materials and Methods
3. Results
Molecular Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Gender | Age at Diagnosis | Method of Screening (GCMS); -Neonatal -Newborn -Family | First Symptoms | Therapeutic Management | Current Age, Clinical Status and History | IVD Genotype * | |
---|---|---|---|---|---|---|---|
1 | F | neonatal | newborn | adaptation period complicated with congenital infection | special nutritional formula for IVA, Supplementation of Gly and carnitine introduced since diagnosis; good adherence | Age: 5 years normal clinical condition with no complications-4 mild decompensations with no severe complications | c.[1133G>A]; [(1133G>A)] p.(Gly378Asp)/p.(Gly378Asp) |
2 | M | neonatal | symptomatic | intoxication syndrome: failure to thrive, dehydration, hypotonia ammonia level—761 µmol/l at diagnosis-decompensation | low-protein diet+ special nutrition formula for IVA, Supplementation of Gly and carnitine introduced since diagnosis; satisfactory adherence | Age: 7 years moderate developmental delay, gastrostomy at the age of 4.5 during one of metabolic decompensation, than removed | Na |
3 | M | neonatal | symptomatic | since birth: hypotonia, apathy, failure to thrive, vomits, specific odour | special nutrition formula for IVA, supplementation of Gly and carnitine introduced since diagnosis; good adherence | Age: 5 years normal clinical condition, average IQ—lower limit of the norm no metabolic decompensations | c.[466C>G(;)879dup] p.(Leu156Val)/p.(Pro294Alafs*38) |
4 | F | neonatal | Family history positive for IVA (first child died at the age of 8 days due to IVA) | besides light hypotonia no worrying symptoms | special nutrition formula for IVA, supplementation of Gly and carnitine introduced since diagnosis; good adherence | Age: 4 years normal clinical condition and development—2 metabolic decompensations triggered by infections | c.[466C>G(;)1133G> A] p.(Leu156Val)/p.(Gly378Asp) |
5 | M | neonatal | symptomatic | intoxication syndrome: vomiting, poor general condition—respiratory failure, sweaty foot odour | low-protein diet, supplementation of carnitine introduced since diagnosis; poor adherence | Age: 22 years depression treated with antidepressants, poor adherence to dietary restrictions; 2 metabolic decompensations: first one at diagnosis, second one triggered by infections | Na |
6 | f | 10y | symptomatic | mild mental delay; during 9 and 10 years of age recurrent vomiting and ketosis; inborn toxoplasmosis | low-protein diet, supplementation of carnitine introduced since diagnosis (10 y); poor adherence | Age: 32 years normal clinical condition, gave birth to 2 children -2 decompensations: first at diagnosis, second after 1st childbirth | c.[466C>G(;)560- 1G>A] p.Leu156Val/p.? |
7 | M | 6y | symptomatic | intoxication syndrome: vomiting, encephalopaty, food intolerance | low-Leu diet, supplementation of Gly introduced since diagnosis (6 y); good adherence | Age: 25 years normal psycho-motor development, but recurrent vomiting, multiple decompensatios till diagnosis—since diet introduction—no episodes | c.[(969+1_970-1)_(1147+1_1148-1)del]; [((969+1_970-1)_(1147+1_1148-1)del)] p.?/p.? |
8 | F | neonatal | symptomatic | good clinical condition | low-protein diet, supplementation of carnitine introduced since diagnosis; good adherence | Age: 11 years normal psycho-motor development—one metabolic decompensation —at diagnosis | c.[941C>T(;)1132G> A] p.(Ala314Val)/p.(Gly378Ser) |
9 | M | 5y | symptomatic | metabolic decompensation: vomiting, poor nutritional status; cerebral palsy | low-protein diet, supplementation of carnitine introduced since diagnosis (5 y); satisfactory adherence | Age: 25 years delayed psycho-motor development—one metabolic decompensation—at diagnosis | Na |
10 | M | neonatal | family (first child died) | good clinical status | low-protein diet + special formula (Prosobee), supplementation of Gly and carnitine; good adherence | Age: 29 years good clinical, and psychological condition—one decompensation due to bacterial tonsillitis (fever and vomiting) | c.[(969+1_970-1)_(1147+1_1148-1)del]; [((969+1_970-1)_(1147+1_1148-1)del)] p.?/p.? |
IVD Variant | Reporting Data * | ||||||
---|---|---|---|---|---|---|---|
cDNA Level | Protein Level | No of Alleles | Type | Status ** | HGMD | ClinVar | PIMID |
c.466C>G | p.(Leu156Val) | 3 | missense | novel 1 | na | Na | no citation |
c.560-1G>A | p.? | 1 | splice-site | known | na | RCV000410323.1 (likely pathogenic-IVA) | no citation |
c.879dup | p.(Pro294Alafs * 38) | 1 | frameshift | known | CI001574 (IVA) | RCV000555769.1 (pathogenic–IV) | 10677295 |
c.941C>T | p.(Ala314Val) | 1 | missense | known | CM983435 (IVA) | RCV000080003.11(pathogenic–not provided) RCV000003749.9 (pathogenic-IVA) | 9665741, 23757202 26018748, 26937393 |
969+1_970-1)_(1147+1_1148-1)del | p.? | 4 | deletion (ex.10-11) | known | CP124273 (IVA) | Na | 22090376 |
c.1132G>A | p.(Gly378Ser) | 1 | missense | Novel 1 | na | Na | no citation |
c.1133G>A | p.(Gly378Asp) | 3 | missense | known | BM0867669 (IVA?) | Na | 19089597 |
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Szymańska, E.; Jezela-Stanek, A.; Bogdańska, A.; Rokicki, D.; Ehmke vel Emczyńska-Seliga, E.; Pajdowska, M.; Ciara, E.; Tylki-Szymańska, A. Long Term Follow-Up of Polish Patients with Isovaleric Aciduria. Clinical and Molecular Delineation of Isovaleric Aciduria. Diagnostics 2020, 10, 738. https://doi.org/10.3390/diagnostics10100738
Szymańska E, Jezela-Stanek A, Bogdańska A, Rokicki D, Ehmke vel Emczyńska-Seliga E, Pajdowska M, Ciara E, Tylki-Szymańska A. Long Term Follow-Up of Polish Patients with Isovaleric Aciduria. Clinical and Molecular Delineation of Isovaleric Aciduria. Diagnostics. 2020; 10(10):738. https://doi.org/10.3390/diagnostics10100738
Chicago/Turabian StyleSzymańska, Edyta, Aleksandra Jezela-Stanek, Anna Bogdańska, Dariusz Rokicki, Ewa Ehmke vel Emczyńska-Seliga, Magdalena Pajdowska, Elżbieta Ciara, and Anna Tylki-Szymańska. 2020. "Long Term Follow-Up of Polish Patients with Isovaleric Aciduria. Clinical and Molecular Delineation of Isovaleric Aciduria" Diagnostics 10, no. 10: 738. https://doi.org/10.3390/diagnostics10100738