Individuals with EFL1 mutations meet the clinical criteria for SDS
| . | Patient P1 . | Patient P2 . | Patient P3 . |
|---|---|---|---|
| Sex | M | F | F |
| Geographic origin | France | Africa Guinea | France |
| Consanguinity | No | Yes | No |
| Birth features | At term | At term | At term |
| Weight | 2840 (<3 centile) | 2640 g (2.5 centile) | 2100 g (0.1 centile) |
| Height | 47 cm (3 centile) | 46 cm (1.7 centile) | 45 cm (1.2 centile) |
| Head circumference | NA | 32.5 cm (6.8 centile) | NA |
| Evidence of bone marrow failure | |||
| Initial manifestation and age at presentation | Thrombocytopenia, age 17 y | Failure to thrive, age 1.5 y | Anemia, failure to thrive age, 1.2 mo |
| Neutropenia | Mild | Severe | Mild |
| Absolute neutrophil count (×109/L), median (min-max) | 1.05 (1.0-3.9) | 8.2 (1.0-37) | 2.48 (1.83-4.0) |
| G-CSF | No | No | No |
| Red cell transfusion | No | No | Yes, during first year |
| Hemoglobin (g/L), median (min-max) | 118 (75-144) | 104 (85-137) | 114 (74−182) |
| Thrombocytopenia | Severe | Mild | During follow up, thrombocytopenia (51 × 109/L) was observed only once, without hemorrhagic symptoms; count recovered spontaneously |
| Platelets (×109/L), median (min-max) | 32 (13-168) | 110 (47-231) | 201 (51-326) |
| Reticulocytes (×109/L) | 109 | 72 | 73 |
| MCV (fL) | 90 | 94 | 103 |
| HbF (%) | NA | 5.8 (age 8 y) | NA |
| Platelet transfusion | No | No | No |
| Pancytopenia | Yes, after age 30 y | No | No |
| Bone marrow cellularity | Low (<5%); 2 bone marrows (at age 28 y) reviewed; no myeloid maturation arrest; segmentation defect in 8-22% of mature neutrophils | Low; at age 8 y, no myeloid maturation arrest; segmentation defect in 35% of mature neutrophils | Normal in the first year of life, mildly decreased on the 3 bone marrow smears >1 y old; erythroblastopenia age 4 mo; no myeloid maturation arrest age 5 y, no erythroblastopenia; segmentation defect in 8% of mature neutrophils |
| Bone marrow cytogenetics | Normal | Normal | Normal |
| Evidence of pancreatic dysfunction | Yes, age 27 y | Yes, age 5 y | Yes, age 6 mo |
| Diagnosis of pancreatic insufficiency | Yes | Yes | Yes |
| Pancreatic enzyme therapy | Yes | Yes | Yes |
| Pancreatic MRI | Lipomatosis | No lipomatosis | No MRI, but hyperechogenicity on US |
| Chronic diarrhea | Yes | Yes | Yes |
| Fecal elastase | Low (<200 μg/g feces) | Low (<200 μg/g feces) | Very low (<100 μg/g feces) |
| Vitamin A | Normal | Low | Low |
| Vitamin D | Normal | Normal | Normal |
| Vitamin E | NA | Normal | Normal |
| Liver | Portal hypertension with splenomegaly. Fibrosis evaluated on CT scan and liver biopsy age 29 y; virology negative | Normal liver MRI; elevated liver enzymes AST/ALT (50-170 IU/L), then spontaneous recovery; no biopsy | Normal liver MRI; elevated liver enzymes AST/ALT (60-120 IU/L); no biopsy |
| Skeletal abnormalities | Claudication and atraumatic femoral neck fracture at 5 y of age; severe osteoporosis, polyepiphyseal and metaphyseal dysplasia with major bilateral genu valgum, patellar luxation, hip subluxation and bilateral oval femoral heads; surgery for genu valgum complicated by osteitis, but outcome was favorable; coxa plana and metaphyseal chondrodysplasia noted at age 29 y | No abnormalities | Metaphyseal dysplasia; skeletal defects of the vertebrae, limbs and ribs; pectus carinatum |
| Bone density | Low, T score (vertebrae) −3.2 SD | Not evaluated | Not evaluated |
| Growth impairment | Short stature −2.6 SD; no therapy | Short stature −3 SD (not improved by pancreatic enzyme replacement); GH deficiency; GH therapy | Short stature −6 SD (not improved by pancreatic enzyme replacement); GH deficiency; no therapy |
| Eyes | Normal | Very severe myopia with low visual acuity | Normal |
| Ears | Normal | Hypoacusia | Normal |
| Cognitive impairment and developmental delay | Normal | Mild; 2-y delay at a special school for learning disabilities; speech delay, but at age 10 y, WISC-IV test result1 normal for age | Mild; 3-y delay in special school for learning disabilities |
| Neurological symptoms | None | Ataxia; nystagmus; CNS MRI normal, but Chiari type I malformation diagnosed at 2 y | None; CNS MRI normal |
| Dentition | Abnormal tooth enamel | Numerous dental caries | Normal |
| Skin abnormalities | No | No | No |
| Recurrent bacterial Infections | No | No | Yes |
| Age at last follow up | 31 y | 14 y | 8 y |
| Vital status | Alive | Alive | Alive |
| . | Patient P1 . | Patient P2 . | Patient P3 . |
|---|---|---|---|
| Sex | M | F | F |
| Geographic origin | France | Africa Guinea | France |
| Consanguinity | No | Yes | No |
| Birth features | At term | At term | At term |
| Weight | 2840 (<3 centile) | 2640 g (2.5 centile) | 2100 g (0.1 centile) |
| Height | 47 cm (3 centile) | 46 cm (1.7 centile) | 45 cm (1.2 centile) |
| Head circumference | NA | 32.5 cm (6.8 centile) | NA |
| Evidence of bone marrow failure | |||
| Initial manifestation and age at presentation | Thrombocytopenia, age 17 y | Failure to thrive, age 1.5 y | Anemia, failure to thrive age, 1.2 mo |
| Neutropenia | Mild | Severe | Mild |
| Absolute neutrophil count (×109/L), median (min-max) | 1.05 (1.0-3.9) | 8.2 (1.0-37) | 2.48 (1.83-4.0) |
| G-CSF | No | No | No |
| Red cell transfusion | No | No | Yes, during first year |
| Hemoglobin (g/L), median (min-max) | 118 (75-144) | 104 (85-137) | 114 (74−182) |
| Thrombocytopenia | Severe | Mild | During follow up, thrombocytopenia (51 × 109/L) was observed only once, without hemorrhagic symptoms; count recovered spontaneously |
| Platelets (×109/L), median (min-max) | 32 (13-168) | 110 (47-231) | 201 (51-326) |
| Reticulocytes (×109/L) | 109 | 72 | 73 |
| MCV (fL) | 90 | 94 | 103 |
| HbF (%) | NA | 5.8 (age 8 y) | NA |
| Platelet transfusion | No | No | No |
| Pancytopenia | Yes, after age 30 y | No | No |
| Bone marrow cellularity | Low (<5%); 2 bone marrows (at age 28 y) reviewed; no myeloid maturation arrest; segmentation defect in 8-22% of mature neutrophils | Low; at age 8 y, no myeloid maturation arrest; segmentation defect in 35% of mature neutrophils | Normal in the first year of life, mildly decreased on the 3 bone marrow smears >1 y old; erythroblastopenia age 4 mo; no myeloid maturation arrest age 5 y, no erythroblastopenia; segmentation defect in 8% of mature neutrophils |
| Bone marrow cytogenetics | Normal | Normal | Normal |
| Evidence of pancreatic dysfunction | Yes, age 27 y | Yes, age 5 y | Yes, age 6 mo |
| Diagnosis of pancreatic insufficiency | Yes | Yes | Yes |
| Pancreatic enzyme therapy | Yes | Yes | Yes |
| Pancreatic MRI | Lipomatosis | No lipomatosis | No MRI, but hyperechogenicity on US |
| Chronic diarrhea | Yes | Yes | Yes |
| Fecal elastase | Low (<200 μg/g feces) | Low (<200 μg/g feces) | Very low (<100 μg/g feces) |
| Vitamin A | Normal | Low | Low |
| Vitamin D | Normal | Normal | Normal |
| Vitamin E | NA | Normal | Normal |
| Liver | Portal hypertension with splenomegaly. Fibrosis evaluated on CT scan and liver biopsy age 29 y; virology negative | Normal liver MRI; elevated liver enzymes AST/ALT (50-170 IU/L), then spontaneous recovery; no biopsy | Normal liver MRI; elevated liver enzymes AST/ALT (60-120 IU/L); no biopsy |
| Skeletal abnormalities | Claudication and atraumatic femoral neck fracture at 5 y of age; severe osteoporosis, polyepiphyseal and metaphyseal dysplasia with major bilateral genu valgum, patellar luxation, hip subluxation and bilateral oval femoral heads; surgery for genu valgum complicated by osteitis, but outcome was favorable; coxa plana and metaphyseal chondrodysplasia noted at age 29 y | No abnormalities | Metaphyseal dysplasia; skeletal defects of the vertebrae, limbs and ribs; pectus carinatum |
| Bone density | Low, T score (vertebrae) −3.2 SD | Not evaluated | Not evaluated |
| Growth impairment | Short stature −2.6 SD; no therapy | Short stature −3 SD (not improved by pancreatic enzyme replacement); GH deficiency; GH therapy | Short stature −6 SD (not improved by pancreatic enzyme replacement); GH deficiency; no therapy |
| Eyes | Normal | Very severe myopia with low visual acuity | Normal |
| Ears | Normal | Hypoacusia | Normal |
| Cognitive impairment and developmental delay | Normal | Mild; 2-y delay at a special school for learning disabilities; speech delay, but at age 10 y, WISC-IV test result1 normal for age | Mild; 3-y delay in special school for learning disabilities |
| Neurological symptoms | None | Ataxia; nystagmus; CNS MRI normal, but Chiari type I malformation diagnosed at 2 y | None; CNS MRI normal |
| Dentition | Abnormal tooth enamel | Numerous dental caries | Normal |
| Skin abnormalities | No | No | No |
| Recurrent bacterial Infections | No | No | Yes |
| Age at last follow up | 31 y | 14 y | 8 y |
| Vital status | Alive | Alive | Alive |
ALT, alanine aminotransferase; AST, aspartate amino transferase; CNS, central nervous system; G-CSF, granulocyte colony-stimulating factor; GH, growth hormone; HbF, hemoglobin F; IU, international unit; MCV, red blood cell mean corpuscular volume; MRI, magnetic resonance imaging; NA, not available; SD, standard deviation; U/K, unknown; WISC-IV, Wechsler Intelligence Scale for Children, Fourth Edition.