Introduction
Prevalence
Biochemistry
Pathogenesis
Methodology and objectives
Aims
Guideline development
Systematic literature review and evidence grading
Evidence level | Criteria |
---|---|
1++ | High quality meta-analyses, systematic reviews of randomised control trials (RCTs), or RCTs with a very low risk of bias. |
1+ | Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias. |
1- | Meta-analyses, systematic reviews or RCTs, or RCTs with a high risk of bias. |
2++ | High quality systematic reviews of case-control or cohort studies or high quality case control or cohort studies with a very low risk of confounding bias, or chance and a high probability that the relationship is causal. |
2+ | Well conducted case-control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal. |
2- | Case-control or cohort studies with a high risk of confounding, bias, or chance and a significant risk that the relationship is not causal. |
3 | Non-analytic studies, e.g. case reports, case series. |
4 | Expert opinion. |
Grade of recommendation | Criteria |
---|---|
A | If level 1 evidence was found (never in this study) |
B | If level 2 evidence was found |
C | If level 3 evidence was found (mainly non-analytical studies such as case reports and case series) |
D | If level 4 evidence was found (mainly expert opinion) |
Recommendations
Clinical presentation
Clinical features (statement #1: grade of recommendation B)
-
EYE: ectopia lentis and/or severe myopia
-
Skeleton: excessive height and length of the limbs (‘marfanoid’ habitus), osteoporosis and bone deformities, such as pectus excavatum or carinatum, genu valgum and scoliosis
-
Central nervous system: developmental delay/intellectual disability, seizures, psychiatric and behavioural problems and extrapyramidal signs
-
Vascular system: thromboembolism
Common presentations (statement #2: grade of recommendation B-C)
Differential diagnosis (statement #3: grade of recommendation B)
Diagnosis
Biochemical diagnosis (statement #4: grade of recommendation C)
Maximizing the sensitivity of biochemical testing (statement #5: grade of recommendation C)
Pre-analytical requirements for biochemical testing (statement #6: grade of recommendation B)
Other causes of hyperhomocystinaemia (statement #7: grade of recommendation C)
Confirmatory testing (statement #8: grade of recommendation B-C)
Role of DNA analysis (statement #9: grade of recommendation B)
Genotype-phenotype correlations (statement #10: grade of recommendation C)
Prenatal diagnosis (statement #11: grade of recommendation C-D)
Newborn screening (statement #12: grade of recommendation C)
Family screening (statement #13: grade of recommendation D)
Treatment targets
Clinical targets of therapy (statement #14: grade of recommendation D)
Biochemical targets of therapy (statement #15: grade of recommendation C)
Pyridoxine-responsive homocystinuria
Assessment of pyridoxine-responsiveness (statement #16: grade of recommendation C-D)
Adverse effects of pyridoxine (statement #17: grade of recommendation D)
Recommended pyridoxine doses (statement #18: grade of recommendation D)
Pyridoxine in non-responsive patients (statement #19: grade of recommendation D)
Role of vitamin B12 and folate supplementation (statement #20: grade of recommendation D)
Dietary management
Approaches to dietary treatment (statement #21: grade of recommendation C-D)
Methionine restriction (statement #22: grade of recommendation D)
Role of L-AA mixtures (statement #23: grade of recommendation D)
Role of cysteine. (statement #24: grade of recommendation D)
Role of energy and micronutrient supplements (statement #25: grade of recommendation D)
Betaine treatment
Role of betaine (statement #26: grade of recommendation C-D)
Recommended betaine doses (statement #27: grade of recommendation C-D)
Side effects of betaine (statement #28: grade of recommendation C-D)
Monitoring (statement #29: grade of recommendation D)
Area | Tests | Frequency |
---|---|---|
Anthropometry | Height & weight | Every clinic visit |
Dietary | Dietary intake analysis | Every clinic visit if on dietary treatment |
Biochemical–metabolic control | tHcy, Met | See text |
Nutritional | Vitamin B12, folate | At least annually |
Blood count, albumin, plasma AA, ferritin, zinc, 25-hydroxyvitamin D | At least annually if on dietary treatment | |
Selenium, essential fatty acids | If concerns about intake | |
Neurodevelopmental/neurological | Clinical examination | Annually |
MRI/EEG | Only if new CNS symptoms | |
Ophthalmological | Eye examination | At least annually |
Neuropsychological ffunction | IQ | At least every 5 years during childhood |
Psychological | Clinical psychology or psychiatric assessment | As required |
Bone density | DEXA | Every 3-5 years from adolescence—unless clinically indicated earlier |
Cardiovascular | Lipid profile, cardiovascular risk factor review | Once in childhood, annually in adulthood |