Early Diagnosis of Classic Homocystinuria in Kuwait through Newborn Screening: A 6-Year Experience
Abstract
:1. Introduction
2. Materials and Methods
2.1. NBS Registry
2.2. DBS Collection Protocol
2.3. Analytical Methods
2.3.1. First DBS
2.3.2. Amino Acids in Repeat (Second) DBS:
2.3.3. Plasma Amino Acids
2.3.4. Plasma Total Homocysteine
2.3.5. Evaluation of Met/Phe Ratio
2.4. Molecular Testing
3. Results
3.1. NBS Registry
3.2. DBS with Hypermethioninemia
3.3. Evaluation of Met/Phe Ratio as a Potential Strategy in Screening for HCU in Kuwait
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Group | Disorder |
---|---|
Endocrinopathies | Congenital hypothyroidism |
Congenital adrenal hyperplasia | |
Aminoacidopathies | Argininosuccinic aciduria (ASA lyase deficiency) |
Citrullinemia (ASA synthetase deficiency) | |
Homocystinuria (cystathionine synthase def.) | |
Maple syrup urine disease (MSUD) | |
Phenylketonuria (PKU) | |
Tyrosinemia (Type I) | |
Fatty Acid Oxidation Disorders | Long chain hydroxy acyl-CoA dehydrogenase deficiency (LCHAD) |
Medium chain acyl-CoA dehydrogenase def. (MCAD) | |
Trifunctional protein deficiency (TFP) | |
Very long chain acyl-CoA dehydrogenase deficiency (VLCAD) | |
Organic Acidemias | 3-Methylcrotonyl-CoA carboxylase deficiency (3MCC) |
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (3HMG-CoA lyase deficiency) | |
Beta ketothiolase deficiency (mitochondrial acetoacetyl CoA thiolase deficiency) | |
Glutaric acidemia type I (GA-I)) | |
Isovaleric acidemia (IVA) | |
Methyl malonic acidemia (MMA) | |
Multiple CoA carboxylase deficiency (MCD) | |
Propionic acidemia (PA) | |
Galactosemia | Classic galactosemia |
Biotinidase Deficiency | |
Hearing Loss | |
Pulse Oximetry for CHD |
2020 | 2019 | 2018 | 2017 | 2016 | 2015 | Total | |
---|---|---|---|---|---|---|---|
Total samples received in NBS laboratory | 56,441 | 56,333 | 55,210 | 59,655 | 57,951 | 52,789 | 338,379 |
Total newborns screened in Kuwait | 51,315 | 50,916 | 48,501 | 53,689 | 52,155 | 47,510 | 304,086 |
Total premature newborns screened ≤ 33 wks | 2823 | 3263 | 3312 | 3350 | 3495 | 3298 | 19,541 |
Newborns ≤ 33 wks (with exclusive high methionine) | 35 | 28 | 43 | 46 | 16 | 12 | 180 |
Newborns >33 wks (with exclusive high methionine) | 49 | 17 | 38 | 73 | 19 | 24 | 220 |
No. of all newborns in Kuwait per CSB | NA | 53,565 | 56,121 | 59,172 | 58,797 | 59,271 | NA |
No. of Kuwaiti newborns per CSB | NA | 32,263 | 33,168 | 33,680 | 33,431 | 33,581 | NA |
No. of Non-Kuwaiti newborns per CSB | NA | 21,302 | 22,953 | 25,492 | 25,366 | 25,690 | NA |
Screened Kuwaiti newborns | 29,762 * | 30,145 | 28,645 | 29,074 | 28,733 | 24,859 | 171,218 |
Screened non-Kuwaiti newborns | 21,553 * | 20,771 | 19,856 | 24,615 | 23,422 | 22,651 | 132,868 |
Newborns not screened under national NBS program | 0 ψ | 2649 | 7620 | 5483 | 6642 | 11,761 | 34,155 |
Percent of coverage of national NBS program (%) | 100 ψ | 94.8 | 84.3 | 89.8 | 87.3 | 75.2 | 88.8 |
Nationality | Sex | Date of Birth (Month. Year) | Gestational Age (Weeks) | Age at NBS Result (Days) | Age at Start of Treatment (Days) | * DNA Variant | Protein Variant | Zygosity | 1st DBS Met Levels (Cutoff 44 μmol/L) | Met/Phe (Cutoff 0.75) | tHcy Levels (Cutoff 15 μmol/L) | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
P1 | KSA | M | 07.2015 | 39 | 5 | NA | NA | NA | NA | 52 | NA | NA |
P2 | K | M | 01.2017 | 38 | 4 | 16 | c.969G>A | Trp323Ter | Homo | 94.2 | 1.5 | 98 |
P3 | K | F | 05.2017 | 39 | 3 | 9 | c.969G>A | Trp323Ter | Homo | 75 | 1.37 | 147 |
P4 | E | F | 03.2019 | 37 | 4 | 5 | c.982G>A | Asp328Asn | Homo | 119 | 1.59 | 132 |
P5 | K | M | 05.2019 | 40 | 5 | 12 | c.1006C>T | Arg336Cys | Homo | 63.2 | 1.02 | 113 |
P6 | K | M | 01.2020 | 37 | 4 | 7 | c.969G>A | Trp323Ter | Homo | 93.28 | 1.9 | 111 |
Cutoff | Sensitivity | Specificity | No. (%) of Positives | PPV % |
---|---|---|---|---|
Met > 44 μmol/L | 1 | 0.998 | 512 э (0.15%) | 1.17 |
Met > 44 μmol/L& Met/Phe > 0.75 | 1 | 0.999 | 174 (0.05%) | 3.4 |
Met/Phe > 0.65 | 1 | 0.996 | 1190 (0.35%) | 0.5 |
Met/Phe > 0.70 | 1 | 0.998 | 658 (0.19) | 0.9 |
Met/Phe > 0.75 ψ | 1 | 0.998 | 417 (0.12%) | 1.4 |
Met/Phe > 0.80 | 1 | 0.999 | 286 (0.08%) | 2.1 |
Met/Phe > 0.85 | 1 | 0.999 | 206 (0.06%) | 2.9 |
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Alsharhan, H.; Ahmed, A.A.; Ali, N.M.; Alahmad, A.; Albash, B.; Elshafie, R.M.; Alkanderi, S.; Elkazzaz, U.M.; Cyril, P.X.; Abdelrahman, R.M.; et al. Early Diagnosis of Classic Homocystinuria in Kuwait through Newborn Screening: A 6-Year Experience. Int. J. Neonatal Screen. 2021, 7, 56. https://doi.org/10.3390/ijns7030056
Alsharhan H, Ahmed AA, Ali NM, Alahmad A, Albash B, Elshafie RM, Alkanderi S, Elkazzaz UM, Cyril PX, Abdelrahman RM, et al. Early Diagnosis of Classic Homocystinuria in Kuwait through Newborn Screening: A 6-Year Experience. International Journal of Neonatal Screening. 2021; 7(3):56. https://doi.org/10.3390/ijns7030056
Chicago/Turabian StyleAlsharhan, Hind, Amir A. Ahmed, Naser M. Ali, Ahmad Alahmad, Buthaina Albash, Reem M. Elshafie, Sumaya Alkanderi, Usama M. Elkazzaz, Parakkal Xavier Cyril, Rehab M. Abdelrahman, and et al. 2021. "Early Diagnosis of Classic Homocystinuria in Kuwait through Newborn Screening: A 6-Year Experience" International Journal of Neonatal Screening 7, no. 3: 56. https://doi.org/10.3390/ijns7030056