When to measure plasma homocysteine and how to place it in context: The homocystinurias
| Oct 02, 2020
Article Category: Review paper
Published Online: Oct 02, 2020
Page range: 39 - 46
DOI: https://doi.org/10.34763/jmotherandchild.20202402si.2016.000007
Keywords
© 2020 Martina Huemer, published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.
Figure 1
Figure 2
Figure 3
Symptoms at disease presentation by age in remethylation disorders (a) and CBS deficiency (b) in estimated order of frequency. There is wide range of ages at presentation and spectrum of severity, from asymptomatic individuals to severely affected patients with multi-system disease.
| (a) Remethylation disorders |
| Feeding difficulties / failure to thrive |
| Muscular hypotonia |
| Developmental / cognitive impairment |
| Seizures |
| Eye disease (nystagmus, visual impairment) The typical eye disease observed in Cbl-related remethylation disorders is generally limited to early onset forms and not present in MTHFR deficiency. |
| Acute metabolic decompensation |
| Cardiac disease (cardiac malformation; cardiomyopathy |
| Atypical haemolytic uraemic syndrome |
| Behavioural problems |
| Movement disorders |
| Stroke / thromboembolic event |
| Anaemia/thrombocytopenia or pancytopenia, megaloblastosis |
| Chronic renal failure |
| Pulmonary hypertension |
| Failure to thrive / weight loss / feeding problems |
| Developmental / cognitive impairment |
| Seizures |
| Muscular hypotonia / muscle weakness |
| Thromboembolism / stroke / pulmonary embolism |
| Psychiatric disease |
| Movement disorder |
| Myelopathy |
| Atypical haemolytic uraemic syndrome |
| Acute metabolic decompensation |
| Chronic renal failure |
| Cardiac disease |
| [5, 9, 10, 14] |
| (b) CBS deficiency (classical homocystinuria) Clinical manifestations are generally more severe in pyridoxine non-responsive disease. |
| Ectopia lentis and/or severe myopia |
| Developmental delay/intellectual disability |
| Thromboembolic events |
| Excessive height and length of the limbs (‘marfanoid’ habitus) |
| Osteoporosis and bone deformities (pectus excavatum or carinatum, genu |
| valgum, scoliosis) |
| Seizures, psychiatric and behavioural problems and extrapyramidal signs |
| [3,4, 15,32] |
Inborn errors and acquired conditions associated with elevated tHcy in blood
high methionine; |
236200 | n | Cbl is expected to be normal (but may be affected by acquired conditions such as decreased su pply). In haptocorrin deficiency, transcobalamin receptor deficiency, MTHFD1 deficiency, and the X-chromosomally inherited HCFC1 defect, tHcy may be but is not consistently elevated. In hypermethioninemias caused by MAT I/III, GNMT, SAHH or ADK deficiencies, tHcy is usually normal or only mildly elevated (usually below 50 μmol/L ) [6, 19, 20]. |
|
low or normal methionine; |
- | - | ↑ | ↓ |
low or normal methionine; |
- | - | ↑ |
↓ |
low or normal methionine; |
261000 | ↑ | often ↓ | |
low or normal methionine; |
261100 | ↑ | often ↓ | |
low or normal methionine; |
275350 | ↑ | Cbl is expected to be normal (but may be affected by acquired conditions such as decreased su pply). In haptocorrin deficiency, transcobalamin receptor deficiency, MTHFD1 deficiency, and the X-chromosomally inherited HCFC1 defect, tHcy may be but is not consistently elevated. In hypermethioninemias caused by MAT I/III, GNMT, SAHH or ADK deficiencies, tHcy is usually normal or only mildly elevated (usually below 50 μmol/L ) [6, 19, 20]. |
|
low or normal methionine; |
277380 | ↑ | Cbl is expected to be normal (but may be affected by acquired conditions such as decreased su pply). In haptocorrin deficiency, transcobalamin receptor deficiency, MTHFD1 deficiency, and the X-chromosomally inherited HCFC1 defect, tHcy may be but is not consistently elevated. In hypermethioninemias caused by MAT I/III, GNMT, SAHH or ADK deficiencies, tHcy is usually normal or only mildly elevated (usually below 50 μmol/L ) [6, 19, 20]. |
|
low or normal methionine; |
614857 | ↑ | Cbl is expected to be normal (but may be affected by acquired conditions such as decreased su pply). In haptocorrin deficiency, transcobalamin receptor deficiency, MTHFD1 deficiency, and the X-chromosomally inherited HCFC1 defect, tHcy may be but is not consistently elevated. In hypermethioninemias caused by MAT I/III, GNMT, SAHH or ADK deficiencies, tHcy is usually normal or only mildly elevated (usually below 50 μmol/L ) [6, 19, 20]. |
|
low or normal methionine; |
277400 | ↑ | Cbl is expected to be normal (but may be affected by acquired conditions such as decreased su pply). In haptocorrin deficiency, transcobalamin receptor deficiency, MTHFD1 deficiency, and the X-chromosomally inherited HCFC1 defect, tHcy may be but is not consistently elevated. In hypermethioninemias caused by MAT I/III, GNMT, SAHH or ADK deficiencies, tHcy is usually normal or only mildly elevated (usually below 50 μmol/L ) [6, 19, 20]. |
|
low or normal methionine; |
277410 | ↑ | Cbl is expected to be normal (but may be affected by acquired conditions such as decreased su pply). In haptocorrin deficiency, transcobalamin receptor deficiency, MTHFD1 deficiency, and the X-chromosomally inherited HCFC1 defect, tHcy may be but is not consistently elevated. In hypermethioninemias caused by MAT I/III, GNMT, SAHH or ADK deficiencies, tHcy is usually normal or only mildly elevated (usually below 50 μmol/L ) [6, 19, 20]. |
|
low or normal methionine; |
277410 | n | Cbl is expected to be normal (but may be affected by acquired conditions such as decreased su pply). In haptocorrin deficiency, transcobalamin receptor deficiency, MTHFD1 deficiency, and the X-chromosomally inherited HCFC1 defect, tHcy may be but is not consistently elevated. In hypermethioninemias caused by MAT I/III, GNMT, SAHH or ADK deficiencies, tHcy is usually normal or only mildly elevated (usually below 50 μmol/L ) [6, 19, 20]. |
|
low or normal methionine; |
236270 | n | Cbl is expected to be normal (but may be affected by acquired conditions such as decreased su pply). In haptocorrin deficiency, transcobalamin receptor deficiency, MTHFD1 deficiency, and the X-chromosomally inherited HCFC1 defect, tHcy may be but is not consistently elevated. In hypermethioninemias caused by MAT I/III, GNMT, SAHH or ADK deficiencies, tHcy is usually normal or only mildly elevated (usually below 50 μmol/L ) [6, 19, 20]. |
|
low or normal methionine; |
250940 | n | Cbl is expected to be normal (but may be affected by acquired conditions such as decreased su pply). In haptocorrin deficiency, transcobalamin receptor deficiency, MTHFD1 deficiency, and the X-chromosomally inherited HCFC1 defect, tHcy may be but is not consistently elevated. In hypermethioninemias caused by MAT I/III, GNMT, SAHH or ADK deficiencies, tHcy is usually normal or only mildly elevated (usually below 50 μmol/L ) [6, 19, 20]. |
|
low or normal methionine; |
236250 | n | Cbl is expected to be normal (but may be affected by acquired conditions such as decreased su pply). In haptocorrin deficiency, transcobalamin receptor deficiency, MTHFD1 deficiency, and the X-chromosomally inherited HCFC1 defect, tHcy may be but is not consistently elevated. In hypermethioninemias caused by MAT I/III, GNMT, SAHH or ADK deficiencies, tHcy is usually normal or only mildly elevated (usually below 50 μmol/L ) [6, 19, 20]. |
|