Pathogenic Biallelic Mutations in ECHS1 in a Case with Short-Chain Enoyl-CoA Hydratase (SCEH) Deficiency-Case Report and Literature Review
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Clinical Summary
3.1.1. Presenting Concerns
3.1.2. Clinical Findings
3.2. Diagnostic Tests
3.2.1. Biologic and Imagistic Assessment
3.2.2. Genetic Analysis
3.2.3. Prenatal Testing and Genetic Diagnosis
3.3. Therapeutic Focus and Assessment
3.4. Follow-Up and Outcome
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Serum Parameters | Measured Value | Normal Range |
---|---|---|
lactate | 43.07 mmol/L | <2.5 mmol/L |
ammonia | 1238 μg/L | 187–869 μg/L |
lactic acid | 3.88 mmol/L | 0.5–2.2 mmol/L |
pyruvate | 0.7 mmol/L | 0.41–0.67 mmol/L |
Plasma Amino Acid | Value | Urinary Organic Acid | Value |
---|---|---|---|
Cystine | ↑ | 3-hydroxyisovaleric acid | ↑↑ |
Valine | ↑ | pyruvic acid | ↑↑ |
Alpha alanine | N | 2-methyl-2,3-dihydroxybutyric | ↑ |
Acyl-carnitine | N |
Patient | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 |
---|---|---|---|---|---|---|---|---|---|---|---|
Ethnicity | Romanian parents | Iraqi-Turkish Jewish/mother Iraqi -Libyan Jewish | Japanese and American parents | Netherlands parents | German parents | French-Canadian parents | NL | NL | Italian parents | Belgian parents | Greek parents |
Genetic mutation | c.476A>G/c.817A>G | c.433C>T/c.476A>G | c.176A>G/ c.476A>G | c.161G>A/c.817A>G | c.229G>C/c.476A>G | c.538A>C/c.476A>G | c.518C>T/c.817A>G | c.476A>G/c.538A>G; | c.476A>G/c.139G>A | c.239C>T/c.817A>C | c.476A>C/ c.542G>T |
Protein effect | p.Gln159Arg/p.Lys273Glu | p.Leu145Phe/ p.Gln159Arg | p.Asn59Ser/ p.Gln159Arg | p.Arg54His/ p.Lys273Glu | p.Glu77Gln/ p.Gln159Arg | p.Thr180Ala/p.Gln159Arg | p.Ala173Val/ p.Lys273Glu | p.Gln159Arg/ p.Thr180Ala | p.Gln159Arg/p.Val47Met | p.Pro80Leu/p.Lys273Glu | p.Gln159Arg/p.Arg181Leu |
Allele source | c.476A>G mother c.817A>G father | NL | c.476A>G mother c.176A>G father | ND | c.476A>G mother father- ND | c.538A>C mother father NA | c.518C>T father c.817A>G mother | Parents- heterozygous for variants | c.476A > G father c.139G > A mother | NL | NL |
Sibling (sex, mutation) | F, dead/c.476A>G/c.817A>G | No | F, dead in 1st day of life: respiratory failure, severe lactic acidosis; mutation NL | NL | M, alive, c.229G>C/= (p.Glu77Gln/=) (heterozygous carrier) | NL | NL | NL | NL | NL | NL |
Sex | F | F | F | M | F | F | M | F | M | M | F |
Age of onset | 3 mo | early infancy | birth | birth | 11 mo | 1 mo | 8 ys | 17 mo | birth | 35 mo | 8 mo |
First neurological signs/symptoms | hypotonia | hypotonia | hypotonia | hypotonia | fist-clenching, teeth-gnashing, horizontal nystagmus | development delay or regression | dyskinesias | hypotonia, lower limbs-flexed on the trunk | lower limb paroxysmal dystonia | encephalopathy | |
Neurologic involvement/characteristics | microcephaly, hypotonia dystonia, spasticity, nystagmus, seizure, inconsolable crying, optic atrophy, global developmental delay, hearing loss? | microcephaly, hypotonia, global developmental delay, optic atrophy, hearing loss | deafness | microcephaly, hypotonia, dystonia, spasticity, inconsolable crying, global developmental regress | dystonia, developmental delay, spastic, nystagmus, hearing loss, optic atrophy | microcephaly, hypotonia, dystonia, nystagmus, optic atrophy, hearing loss | dyskinesias, dystonia | hypotonia, dystonia global developmental delay | hypotonia, limbs spasticity, hearing loss | dystonia, spasticity, mild developmental delay | microcephaly, nystagmus, severe development delay optic atrophy, hearing loss |
Seizure, age of onset | Yes, 6 mo | No | Yes | Yes, 1.3 ys | Yes | Yes / + | No | No | No | No | No |
Feeding difficulties | Yes | Yes | NL | yes | NL | NL | No | NL | NL | No | Yes |
Cardiomyopathy/Cardiac involvement | HCM | transient hypertrophy of the interventricular septum | HCM, cardiac failure | No | No | NL | NL | No | LVH | No | No |
Outcome alive/death (age) | Alive 6 ys | Alive at 7 ys | Death at 4 mo | Death at 7.5 ys | Alive at 31 ys | Alive at 12 ys | Alive at 8 ys | Alive at 4.5 ys | Death at 62 d | Alive 6 ys | Death 9 ys |
Metabolic workup | |||||||||||
Plasma Lactate | High | High | High | ND | High | N | N | High | High | N | High |
Plasma Pyruvate | High | NL | NL | NL | N | NL | N | N | |||
Alanine | N | High | NL | NL | NL | NL | N | NL | High | N | N |
Urinary organic acids | NL | NL | metabolic profiling (amino acid analysis, urine organic acid analysis, acylcarnitine analysis) was unremarkable | NL | NL | severe ketosis and hyperlactaturia (resolved with treatment) | N | normal plasma amino acids, urine organic, and amino acid analysis | NL | NL | NL |
2-methyl-2,3-dihydroxybutyric acid | High | High | N | NL | N | NL | N | NL | High | N | N |
MRI changes | brain atrophy, hyperintensity within putamen, cavitation at this level, extensive diffuse white matter changes | atrophy of the cerebellum and brain stem, mild ventricular dilatation, generalized atrophy of the grey matter, thinning of the corpus callosum | moderate brain atrophy, low intensity in cerebral white matter | Extensive brain atrophy, widening of the subarachnoid space and of the ventricular system | no atrophy, hyperintensity in nucleus caudatus and putamen | cerebellar atrophy, hyperintense T2-weighted images in the putamen, globus palidus, caudate nuclei | regions of increased T2 and FLAIR signal and of hypointense T1 signal in the globus pallidus bilaterally with mild diffusion restriction | globus pallidus, putamen, caudate nuclei, basal ganglia T2 hyperintensity | asymmetric ventricular dilatation, partial agenesis of the posterior part of the corpus callosum, basal ganglia, a slight increase of T2 WM signal intensity, germinal cyst in the thalamo-caudate notch | asymmetric cavitation of globus pallidus, bilateral T2-WI hyperintensity, restricted diffusion | globus pallidus, caudate nuclei T2 hyperintensity |
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Muntean, C.; Tripon, F.; Bogliș, A.; Bănescu, C. Pathogenic Biallelic Mutations in ECHS1 in a Case with Short-Chain Enoyl-CoA Hydratase (SCEH) Deficiency-Case Report and Literature Review. Int. J. Environ. Res. Public Health 2022, 19, 2088. https://doi.org/10.3390/ijerph19042088
Muntean C, Tripon F, Bogliș A, Bănescu C. Pathogenic Biallelic Mutations in ECHS1 in a Case with Short-Chain Enoyl-CoA Hydratase (SCEH) Deficiency-Case Report and Literature Review. International Journal of Environmental Research and Public Health. 2022; 19(4):2088. https://doi.org/10.3390/ijerph19042088
Chicago/Turabian StyleMuntean, Carmen, Florin Tripon, Alina Bogliș, and Claudia Bănescu. 2022. "Pathogenic Biallelic Mutations in ECHS1 in a Case with Short-Chain Enoyl-CoA Hydratase (SCEH) Deficiency-Case Report and Literature Review" International Journal of Environmental Research and Public Health 19, no. 4: 2088. https://doi.org/10.3390/ijerph19042088
APA StyleMuntean, C., Tripon, F., Bogliș, A., & Bănescu, C. (2022). Pathogenic Biallelic Mutations in ECHS1 in a Case with Short-Chain Enoyl-CoA Hydratase (SCEH) Deficiency-Case Report and Literature Review. International Journal of Environmental Research and Public Health, 19(4), 2088. https://doi.org/10.3390/ijerph19042088