Table 2 Clinical, biochemical, and radiological features of 31 patients with RRM2B deficiency
From: The natural history of infantile mitochondrial DNA depletion syndrome due to RRM2B deficiency
Clinical features | Number of patients during clinical course | ||
|---|---|---|---|
Neuromuscular system | 31/31 (100%) | ||
Truncal hypotonia | 30/31 (96.7%) | ||
Encephalopathy | 15/31 (48.4%) | ||
Gross motor delay | 15/31 (48.4%) | ||
Feeding difficulty | 14/31 (45.2%) | ||
Seizures | 12/31 (38.7%) | ||
Lack of head control | 12/31 (38.7%) | ||
Generalized weakness | 10/31 (32.2%) | ||
Loss of reflexes | 9/31 (29%) | ||
Discoordinated suck | 9/31 (29%) | ||
Ptosis | 6/31 (19.3%) | ||
Progressive external ophthalmoplegia | 6/31 (19.3%) | ||
Discoordinated swallow | 6/31 (19.3%) | ||
Peripheral neuropathy | 2/31 (6.5%) | ||
Nystagmus | 1/31 (3.2%) | ||
Dystonia | 1/31 (3.2%) | ||
Respiratory system | 18/31 (58%) | ||
Respiratory distress | 17/31 (54.8%) | ||
Respiratory failure | 15/31 (48.4%) | ||
Pneumonia | 5/31 (16.1%) | ||
Renal system | 17/31 (54.8%) | ||
Tubulopathy | 16/31 (51.6%) | ||
Aminoaciduria | 7/31 (22.5%) | ||
Glycosuria | 5/31 (16.1%) | ||
Microalbuminuria | 3/31 (9.7%) | ||
Elevated RBP/Cr | 3/31 (9.7%) | ||
Calciuria | 2/31 (6.5%) | ||
Elevated NAG/Cr | 3/31 (6.5%) | ||
Phosphaturia | 1/31 (3.2%) | ||
Nephrocalcinosis | 6/31 (19.3%) | ||
Auditory system | 11/31 (36%) | ||
Sensorineural hearing loss | 11/31 (36%) | ||
Gastrointestinal system | 10/31 (32%) | ||
Recurrent vomiting | 7/31 (22.5%) | ||
Feed intolerance | 3/31 (9.7%) | ||
Chronic diarrhea | 2/31 (6.5%) | ||
Ophthalmological system | 4/31 (12.9%) | ||
Pigmentary retinopathy | 2/31 (6.5%) | ||
Cataract | 1/31 (3.2%) | ||
Megacornea | 1/31 (3.2%) | ||
Hematological system | 4/31(12.9%) | ||
Anemia | 4/31 (12.9%) | ||
Cardiovascular system | 4/31 (12.9%) | ||
Left ventricular hypertrophy | 2/31 (6.5%) | ||
Cardiomyopathy | 1/31 (3.2%) | ||
Ventricular septal defect | 1/31 (3.2%) | ||
Growth abnormalities | 16/31 (51.6%) | ||
Failure to thrive | 16/31 (51.6%) | ||
Microcephaly | 5/31 (16.1%) |
Biochemical features | Number of patients during clinical course | ||
|---|---|---|---|
General biochemistry | |||
Hyperlactatemia | 31/31 (100%) | ||
Elevated lactate/pyruvate ratio | 4/5 (80%) | ||
Elevated CSF lactate | 8/10 (80%) | ||
Elevated creatine kinase | 8/19 (42%) | ||
Low free carnitine | 3/11 (27%) | ||
Plasma amino acids | |||
Elevated alanine | 10/16 (63%) | ||
Elevated branched chain amino acids | 4/16 (25%) | ||
Multiple low species | 3/16 (19%) | ||
Normal | 4/16 (25%) | ||
Urine organic acids | |||
Elevated lactate | 12/16 (75%) | ||
Elevated pyruvate | 5/16 (31%) | ||
Elevated ketones | 7/16 (43%) | ||
Elevated Krebs cycle intermediates | 6/16 (38%) | ||
Normal | 3/16 (19%) | ||
Hypocalcemia | 2/31 (6%) | ||
Skeletal muscle spectrophotometry | Low | Normal | High |
Complex I | 17/18 | 1/18 | 0/18 |
Complex II | 3/13 | 2/13 | 8/13 |
Complex III | 7/7 | 0/7 | 0/7 |
Complex IV | 20/20 | 0/20 | 0/20 |
Complex V | 3/6 | 1/6 | 2/6 |
Complex I+III | 4/4 | 0/4 | 0/4 |
Complex II+III | 9/12 | 2/12 | 1/12 |
Citrate synthase | 1/13 | 4/13 | 8/13 |
Muscle histopathology | |||
Ragged-red fibers | 12/19 | ||
Increased SDH | 7/19 | ||
COX-deficient fibers | 16/19 | ||
Lipid storage | 14/19 | ||
Atrophic fibers | 2/19 | ||
Radiological features | |||
MRI head | |||
Generalized hypo/demyelination | 1/14 | ||
White matter abnormalities | 2/14 | ||
Generalized atrophy | 2/14 | ||
Normal | 9/14 | ||
MR spectroscopy | |||
Elevated lactate | 8/10 | ||
Localization: | |||
Basal ganglia | 5/8 | ||
White matter | 3/8 | ||
CSF | 1/8 | ||
Not stated | 3/8 | ||
Reduced choline/NAA | 1/10 | ||
Normal | 2/10 | ||
