Table 1.
Clinical features of individuals with MICU1 variants
| Family 1 | Family 2 | Family 3 | Family 4 | Family 5 | Family 6 | Family 7 | Family 8 | Family 9 | Family 10 | |
|---|---|---|---|---|---|---|---|---|---|---|
| Gender (age) | M (16) | F (10) | F (14) | F (14) | M (26) M (24) M (24) |
F (7) | F (6) | M (6) M (14) |
M (10) | M (4) |
| Age at presentation | 9 years | 2 years | 10 years | 11 years | 23 years 21 years 21 years |
2 years | 4 years | 6 years 14 years |
10 years | 3 years |
| Age at last examination | 15 years | 10 years | 10 years | 13 years | 26 years 24 years 24 years |
7 years | 4 years | 6 years 14 years |
10 years | 3 years |
| Variant | p.Q185* (HOM) | p.Q185* (HOM) | p.Q185* (HOM) | p.Q185* (HOM) | p.Q185* (HOM) | p.Q185* (HOM) | p.Q185* (HET)/Exon 9 and 10 dup (HET) | p.Q185* (HOM) | p.Q185* (HOM) | p.185* (HOM) |
| Developmental delay | + | + | + | + | + | + | + | + | + | + |
| Speech delay | + | + | + | + | + | + | n/a | n/a | + | + |
| Elevated liver transaminases | + | + | + | n/a | + | + | + | + | + | + |
| Elevated CK | + | + | + | n/a | + | + | + | + | + | + |
| Poor growth | + | + | + | − | n/a | + | − | − | − | − |
| Normal serum lactate levels (0.5–1.6 mmol/L) | + | + | + | n/a | +++ | + | + | n/a | + | + |
| Height (%ile) | 5th | 5th | <5th | 50th | n/a | <5th | 25th | 25–50th | 50th | 10th |
| Weight (%ile) | 5th | 25th | n/a | 50th | n/a | <5th | 50th | 25–50th | 50th | 10th |
| HC (%ile) | 50th | 50th | 75th | n/a | n/a | n/a | 25–50th | 50th | 25th | |
| Hypotonia | + | + | − | − | − | − | + | + | − | + |
| Hepatomegaly | − | + Hepatosplenomegaly | + | − | n/a | − | n/a | n/a | − | − |
| Abnormal gait | − | + | − | − | − | n/a | + | + | − | n/a |
| Frequent falls | − | − | − | − | +++ | n/a | + | n/a | − | n/a |
| VSD | − | + | − | − | − | + | − | − | − | − |
| Learning disability | + | − | + | + | + | n/a | n/a | + | + | + |
| Extrapyrimidal signs at which age | − | +10 years | − | − | +++ 25 years 23 years 23 years |
− | − | − | − | +4 years |
| Other features | Muscular cramps Proximal myopathy |
Dysmorphism, abnormal MRI showing white matter changes. Hemolytic anemia, low IgG, B, T, and NK cells. Massive hepatosplenomegaly | Easy fatiguability and muscle pain with walking long distances Increased liver periportal echogenicity on ultrasound abdomen |
Hyperactivity | Calf muscle hypertrophy Seizures Muscular cramps Tremors Postural dystonia |
Dysmorphism: short neck, doughy skin, lax joints, down turned lower lip, tented upper lip, and mild syndactly Coarse liver on ultrasound abdomen |
Positive Gower sign | Seizures Hyperactivity |
Myopathic face Choreoathetoid movement of hands and legs and orofacial dyskinesia | |
| Family history | CS parents | NCS parents (same tribe); three unaffected sisters, two unaffected brothers | CS parents (1st cousins); three unaffected siblings | CS parents; | CS parents; three similarly affected brothers | NCS parents; one unaffected sister | CS parents; two unaffected siblings | CS parents; two similarly affected brothers; one similarly affected sister (deceased at age 2); one unaffected sister | CS parents | CS parents |
HOM homozygous, F female, M male, “+” present, “−” absent, HC head circumference, %ile percentile, n/a not available, VSD ventricular septal defect, CS consanguineous, NCS nonconsanguineous