Summary of clinical phenotype for each of the cases in the cohort
| Case no. . | . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical feature . | 1 . | 2 . | 3 . | 4 . | 5 . | 6 . | 7 . | 8 . | 9 . | 10 . | 11 . | 12 . |
| Microcytic anemia | + | + | + | + | + | + | + | + | + | + | + | + |
| SA | + | + | + | ND | + | + | + | + | + | + | + | + |
| B lymphopenia and/or hypogamma globulinemia | + | + | + | + | + | + | +/− | +/− | + | + | −* | |
| Recurrent inflammatory epsidodes | + | + | + | + | + | + | + | + | +† | + | + | + |
| Developmental delay | + | + | + | + | + | + | + | + | + | + | + | −* |
| Sensorineural deafness | + | + | − | − | + | − | + | + | − | − | − | |
| Ataxia/cerebellar signs | − | − | + | + | + | + | − | − | ||||
| Seizures | − | − | + | + | + | − | + | + | − | − | − | − |
| Neuroimaging abnormalities | Cerebral atrophy | Cerebral atrophy | Cerebral atrophy; decreased cerebellar perfusion | Communicating hydrocephalus; macrocephaly | − | − | Cerebral atrophy; abnormal enhancement of external capsule and thalamus | Delayed white matter myelination | − | − | − | |
| Nephrocalcinosis | + | + | − | − | + | − | − | |||||
| Aminoaciduria ± hyperalaninemia | + | + | + | − | + | + | + | + | − | |||
| RP | + | + | + | − | − | + | − | |||||
| Cardiomyopathy (diagnosed during life) | − | − | − | + | − | − | + | − | − | |||
| Splenomegaly | − | − | +/− | + | +/− | +/− | − | − | − | − | ||
| Lactic acidosis | + | + | − | + | ||||||||
| Brittle hair | + | + | + | |||||||||
| Other features | Ichthyotic skin changes; abnormal high amplitude slow activity on EEG | Increased urinary TCA intermediates | Renal tubular Fanconi syndrome | Malabsorption; small bowel villous atrophy; avascular necrosis (hip) | Pancreatic insufficiency | Hypercalciuria | Torticollis | Hypertension | Nonspecific metabolic myopathy on muscle biopsy | |||
| Case no. . | . | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical feature . | 1 . | 2 . | 3 . | 4 . | 5 . | 6 . | 7 . | 8 . | 9 . | 10 . | 11 . | 12 . |
| Microcytic anemia | + | + | + | + | + | + | + | + | + | + | + | + |
| SA | + | + | + | ND | + | + | + | + | + | + | + | + |
| B lymphopenia and/or hypogamma globulinemia | + | + | + | + | + | + | +/− | +/− | + | + | −* | |
| Recurrent inflammatory epsidodes | + | + | + | + | + | + | + | + | +† | + | + | + |
| Developmental delay | + | + | + | + | + | + | + | + | + | + | + | −* |
| Sensorineural deafness | + | + | − | − | + | − | + | + | − | − | − | |
| Ataxia/cerebellar signs | − | − | + | + | + | + | − | − | ||||
| Seizures | − | − | + | + | + | − | + | + | − | − | − | − |
| Neuroimaging abnormalities | Cerebral atrophy | Cerebral atrophy | Cerebral atrophy; decreased cerebellar perfusion | Communicating hydrocephalus; macrocephaly | − | − | Cerebral atrophy; abnormal enhancement of external capsule and thalamus | Delayed white matter myelination | − | − | − | |
| Nephrocalcinosis | + | + | − | − | + | − | − | |||||
| Aminoaciduria ± hyperalaninemia | + | + | + | − | + | + | + | + | − | |||
| RP | + | + | + | − | − | + | − | |||||
| Cardiomyopathy (diagnosed during life) | − | − | − | + | − | − | + | − | − | |||
| Splenomegaly | − | − | +/− | + | +/− | +/− | − | − | − | − | ||
| Lactic acidosis | + | + | − | + | ||||||||
| Brittle hair | + | + | + | |||||||||
| Other features | Ichthyotic skin changes; abnormal high amplitude slow activity on EEG | Increased urinary TCA intermediates | Renal tubular Fanconi syndrome | Malabsorption; small bowel villous atrophy; avascular necrosis (hip) | Pancreatic insufficiency | Hypercalciuria | Torticollis | Hypertension | Nonspecific metabolic myopathy on muscle biopsy | |||
Detailed clinical vignettes describing each child’s clinical course are provided online as supplemental data.
+, feature confirmed during life; −, feature confirmed to be absent during life or at latest follow up; +/−, borderline/mild presence of abnormality or clinical feature; blank cells, insufficient information, usually as feature was not specifically investigated or considered during life; ND, BM ringed sideroblastosis not confirmed but highly likely given similarities to older sibling with confirmed CSA (discussed in “Family history”).
Low normal results when tested early in life; see “Immunodeficiency” section for explanation of rationale for child’s inclusion within cohort.
Clinical course characterized by recurrent inflammatory episodes with gastrointestinal upset and raised inflammatory markers, although high fevers were not recalled as a prominent feature.