Table 13.

Recommended Surveillance for Individuals with Isolated Methylmalonic Acidemia

ManifestationEvaluationFrequency/Comment
Poor growth Measurement of growth & head circumferenceAt each visit
Metabolic
abnormalities 		Screening lab testing, incl:
  • Plasma amino acids 1
  • Plasma & urine MMA levels
  • Serum acylcarnitine profile & free & total carnitine levels
  • Blood chemistries 2
  • CBC
At least every 6-12 mos; more frequently in infants or in those who are unstable or require frequent changes in mgmt
Renal
insufficiency 3
  • Measurement of creatinine, cystatin-C, & (if available) GFR (e.g., iohexol plasma decay) 4, 5, 6
  • Renal imaging
  • Bone mineral density (DXA) 7
  • Early referral to nephrologist is critical for consideration of renoprotective measures.
  • Monitoring of renal comorbidities by multidisciplinary team
At least annually, or as clinically indicated
Liver disease
  • Liver ultrasound
  • Measurement of liver transaminases & alpha-fetoprotein 8
Annually, or as clinically indicated 9
Delayed
acquisition of developmental
milestones 		Monitor developmental milestones. 10At each visit
Neuropsychological testing using age-appropriate standardized assessment batteries, development of an individualized education plan.As clinically indicated
Standardized quality-of-life assessment tools for affected persons & parents/caregiversAs needed
Movement
disorder 		Assessment for clinical symptoms & signs of mvmt disorders, severity, & responses to treatment, PT, & pharmacologic interventionsAt each visit
Optic nerve
atrophy 		Ophthalmology eval 11At least annually, or as clinically indicated
Hearing loss 12 Audiology evalAt least annually in childhood & adolescence, or as clinically indicated

CBC = complete blood count; GFR = glomerular filtration rate; PT = physical therapy

1.

Frequent monitoring of plasma amino acids is necessary to avoid deficiencies of essential amino acids (particularly isoleucine, valine, and methionine) as a result of excessive protein restriction and the development of acrodermatitis-enteropathica-like cutaneous lesions in methylmalonic aciduria, as in other organic acidurias (glutaric aciduria-I) and amino acid disorders (maple syrup urine disease) [De Raeve et al 1994].

2.

Including Na+, K+, CI–, glucose, urea, creatinine, bicarbonate, AST, ALT, alkaline phosphatase, bilirubin (T/U), triglycerides, and cholesterol

3.

Comorbidities of renal disease may include anemia, acidosis, hyperuricemia, secondary hyperparathyroidism, osteopenia/osteoporosis, hypertension, and short stature. In addition to cystatin-C, biochemical markers of bone health (Ca, P, alkaline phosphatase, parathyroid hormone, 1.25 dihydroxy-vit D (D3), and uric acid should be assessed periodically.

4.

Combined equations based on creatinine and cystatin-C and measured GFR by iohexol clearance or other methods are expected to reflect more accurately the kidney function in people with MMA [Dao et al 2021]. Age-appropriate formulas to estimate GFR are available for both pediatric patients and adult patients.

5.

To allow for early referral to nephrologist and appropriate timing of renal transplantation when needed [van't Hoff et al 1999, Kruszka et al 2013].

6.

Nephrotoxic medication should be avoided (see Agents/Circumstances to Avoid).

7.

DXA scan is typically done in older individuals, starting in adolescence, unless there is evidence for renal disease earlier.

8.
9.

Particularly in individuals with severe MMA subtypes

10.

Enrollment in early intervention programs for physical, occupational, and speech therapy is recommended.

11.

To assess for optic nerve thinning/pallor

12.

Hearing loss can occur in isolated MMA and may be a result of episodes of metabolic decompensation.

From: Isolated Methylmalonic Acidemia

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