Table 1 Cohort of patients diagnosed with adult-onset of Cobalamin C disease

1

18/18

F

Lower limbs weakness

Neuropathy, psychiatric symptoms, seizures

273.3

c.1A > G

p.Met1Val

c.445_446del

p.Cys149HisfsTer16

[8]

2

18/19

F

Lower limbs weakness

Psychiatric symptoms, ataxia, cortical atrophy, thoracic cord atrophy, scoliosis

138

c.482G > A

.Arg161Gln

c.445_446del

p.Cys149HisfsTer16

[32]

3

18/19

F

Neuropsychiatric symptoms

Cognitive decline, neuropathy, psychiatric symptoms, ataxia, hyperintensity of basal ganglia and cerebellum, cervical and thoracic cord atrophy, scoliosis

69.5

c.482G > A

p.Arg161Gln

c.445_446del

p.Cys149HisfsTer16

[8]

4

18/20

M

Neuropsychiatric symptoms

Neuropathy, psychiatric symptoms, lower limb weakness, cortical atrophy, thoracic cord atrophy, scoliosis

193.4

c.482G > A

p.Arg161Gln

c.656_658del

p.Lys220ArgfsTer71

[8]

5

18/20

M

HUS

Nephrotic syndrome, hematuria, renal failure

–

c.82-12_82-9delTTTC

c.271dupA

p.Arg91LysfsTer14

[18]

6

18/39

F

Pulmonary embolism

Cognitive decline, neuropathy, psychiatric symptoms, myoclonus, dysarthria, dysmetria, adiadochocinesia, tetraparesis, seizures, recurrent thrombosis, glomerulonephritis, leukoencephalopathy, cortical atrophy, corpus callosum agenesis

172

c.365A > G

p.His122Arg

c.457C > T

p.Arg153Ter

[33]

7

19/19

F

HUS

Acute renal failure, nephrotic syndrome, hematuria, severe neurologic impairment

285

c.566G > A

p.Arg189His

c.271dupA

p.Arg91LysfsTer14

[31]

8

19/20

F

Psychiatric symptoms, cognitive decline

Anemia, cortical atrophy, thoracic cord atrophy, scoliosis

155

c.452A > G

p.His151Ala

c.452A > G

p.His151Ala

[32]

9

19/20

F

Neuropsychiatric symptoms, renal disease

Cognitive decline, psychiatric symptoms, renal dysfunction, anemia, cortical atrophy, cervical and thoracic cord atrophy

115.2

c.452A > G

p.His151Ala

c.452A > G

p.His151Ala

[8]

10

19/20

M

Legs paraplegia

Cognitive decline, neuropathy, bilateral legs paraplegia, deep veins thrombosis

27.9

–

–

[12]

11

19/29

M

Lower limbs weakness, cognitive decline

Ataxia, cortical atrophy, thoracic cord atrophy

114.2

c.482G > A

p.Arg161Gln

c.658_660del

p.Ala221GlyfsTer7

[8]

12

20/21

M

HUS

Renal failure, malignant hypertension

185

c.389A > G

p.Tyr130Cys

c.271dupA

p.Arg91LysfsTer14

[17]

13

20/22

F

Psychiatric symptoms

Isolated psychiatric presentation

128

c.365A > G

p.His122Arg

c.609G > A

p.Trp203Ter

[8]

14

20/22

M

Neurological symptoms

Cognitive decline, pyramidal signs, lower limb weakness, seizures, cortical atrophy, anorexia

230.97

c.482G > A

p.Arg161Gln

c.609G > A

p.Trp203Ter

[34]

15

20/34

F

Decline in renal function

Proteinuria, microhematuria, anemia

90

c.388 T > C

p.Tyr130His

c.666C > A

p.Tyr222Ter

[21]

16

22/22

F

Lower limbs weakness, cognitive decline

Increased tendon reflex in upper limbs, decreased tendon reflex in lower limbs, positive Babinski sign, neuropathy

79.8

c.482G > A

p.Arg161Gln

c.609G > A

p.Trp203Ter

[35]

17

23/23

M

Ataxia

Cognitive decline, numbness and partial paralysis in the lower limbs

167

c.392_394del

p.Gln131del

c.392_394del

p.Gln131del

[13]

18

23/23

M

Lower limbs weakness

Mild memory impairment, progressive spastic paraplegia, bilateral pyramidal tract signs

93.6

c.482G > A

p.Arg161Gln

c.609G > A

p.Trp203Ter

[32]

19

24/24

M

Neuropsychiatric symptoms

Cognitive decline, pyramidal signs, hyporeflexia, hyperesthesia, lower limbs weakness, anorexia, coma

100.22

c.482G > A

p.Arg161Gln

c.217C > T

p.Arg73Ter

[34]

20

24/25

F

Progressive gait disturbance

Myelopathy, lower limb weakness

125

c.347 T > C

p.Leu116Pro

c.271dupA

p.Arg91LysfsTer14

[36]

21

24/31

F

Neuropsychiatric symptoms

Lower limbs weakness, longitudinally extensive transverse myelitis in cervical spinal cord

75.4

c.463G > C

p.Gly155Arg

c.609G > A

p.Trp203Ter

[8]

22

25/27

M

Neurological symptoms

Cognitive decline, lower limbs weakness, pyramidal signs, cortical atrophy, coma

111.88

c.482G > A

p.Arg161Gln

c.440_441del

p.Cys149HisfsTer32

[34]

23

26/26

M

Lower limbs weakness

Progressive spastic paraplegia, pyramidal signs, generalized tonic–clonic seizures, optic nerve atrophy, cortical atrophy

97.7

c.565C > A

p.Arg189Ser

c.567dupT

p.1190YfsTer13

[32]

24

26/28

F

Maculopathy

Decreased central vision, mild photoaversion

–

c.482G > A

p.Arg161Gln

c.271dupA

p.Arg91LysfsTer14

[20]

25

26/30

M

Sensorimotor neuropathy

Ataxia, anorexia, impaired short-term memory, confusion, cognitive decline, deep vein thrombosis, peripheral pulmonary embolism, depression

264

c.482G > A

p.Arg161Gln

c.82-1G > A

[9]

26

26/33

F

Thrombotic microangiopathy

Nephrotic syndrome, renal failure, anemia

230

c.389A > G

p.Tyr130Cys

c.271dupA

p.Arg91LysfsTer14

[16]

27

28/29

M

Psychiatric symptoms

Cognitive decline, depression, euphoria, sleep disturbance, visual hallucinations, manic psychosis, lower limbs weakness, hyperreflexia, bilateral Babinski sign, visual decline, optic nerve atrophy, cortical atrophy

115.30

c.482G > A

p.Arg161Gln

c.658_660del

p.Ala221GlyfsTer7

[37]

28

28/29

M

Psychiatric symptoms

Euphoria, agitation, irritabilty, aggressiveness, mild memory impairment, bilateral paraplegia, pyramidal tract signs

75.7

c.482G > A

p.Arg161Gln

c.656_658del

p.Lys220ArgfsTer71

[32]

29

29/29

F

Low carnitine on daughter newborn screening

–

147

c.482G > A

p.Arg161Gln

c.81 + 1G > A

[38]

30

29/29

M

Subclinical neuropathy

–

–

–

–

[14]

31

29/29

M

Ataxia

Neuropathy

102.8

c.482G > A

p.Arg161Gln

c.656_658del

p.Lys220ArgfsTer71

[8]

32

29/29

M

Psychiatric symptoms

Seizures

103.3

c.482G > A

p.Arg161Gln

c.567dupT

p.1190YfsTer13

[8]

33

30/32

M

Psychiatric symptoms

Euphoria, agitation, auditory and visual hallucinations, mild memory impairment, paraplegia, pyramidal signs, mild optic nerve atrophy

115.3

c.482G > A

p.Arg161Gln

c.656_658del

p.Lys220ArgfsTer71

[32]

34

31/33

M

Psychiatric symptoms

Insomnia, exaggerated expression, euphoria, increased irritability, thoughts of worthlessness, reduced vocal expression, social withdrawal, anorexia, lower limbs weakness, patellar tendons hyperreflexia, blurred vision, pigmentary retinopathy, optic nerve atrophy, cortical atrophy

65.0

c.482G > A

p.Arg161Gln

c.658_660del

p.Ala221GlyfsTer7

[37]

35

31/36

F

Psychiatric symptoms

Depression and psychosis requiring hospitalization, lower limbs weakness, legs paresthesia, lower limbs hemiplegia, thrombosis

57

c.482G > A

p.Arg161Gln

c.271dupA

p.Arg91LysfsTer14

[39]

36

32/34

F

Sensorimotor neuropathy

Ataxia, apathy, confusion, tetraparesis, anxiety, inability of self-care and communication, respiratory failure, deep vein thrombosis, white matter abnormalities, spinal cord involvement

53.3

c.347 T > C

p.Leu116Pro

c.347 T > C

p.Leu116Pro

[9]

37

32/Deceased

M

Neuropathy, lower limbs weakness

Numbness of extremities, ataxia, dysphagia, paraplegia, optic nerve atrophy, leukoencephalopathy, spinal cord atrophy

–

–

–

[26]

38

33/40

F

Recurrent venous thrombosis

Glomerulonephritis

288

c.365A > G

p.His122Arg

c.271dupA

p.Arg91LysfsTer14

[33]

39

35/35

M

Ataxia

Urinary incontinence, positive Romberg and Babinki signs

136.5

c.482G > A

p.Arg161Gln

c.658_660del

p.Ala221GlyfsTer7

[11]

40

38/39

M

Limb weakness, Ataxia

Neuropathy, scoliosis

67.1

c.80A > G

p.Gln27Arg

c.609G > A

p.Trp203Ter

[8]

41

38/42

M

Seizures

Cognitive decline, leukoencephalopathy

230

–

–

[27]

42

40/40

M

Cognitive decline

Cognitive decline, delirium, auditory hallucinations, ataxia, upper and lower limb rigidity, urinary incontinence, positive Babinski sign, cortical atrophy, cerebellar anomalies

57.2

c.482G > A

p.Arg161Gln

c.1A > G

p.Met1Val

[35]

43

41/42

M

Psychiatric symptoms

Depression, apraxia, ataxia, spasticity, myelopathy, pulmonary embolism, leukoencephalopathy, cervical/dorsal spinal cord atrophy

228

c.565C > A

p.Arg189Ser

c.271dupA

p.Arg91LysfsTer14

[33]

44

44/Deceased

M

Psychiatric symptoms, Cognitive decline

Social withdrawal, dysarthria, ataxia, optic nerve atrophy, deep veins thrombosis and pulmonary embolism, leukoencephalopathy

–

–

–

[26]

45

45/46

M

Depression

Cognitive decline, social withdrawal, insomnia, visual hallucinations, difficulty in following complex reasoning, ataxia, positive Babinski sign, seizures, renal failure, proteinuria, HUS, anemia, leukoencephalopathy, cortical atrophy

130

c.395_397del

p.Arg132del

c.220delA

p.Met74CysfsTer2

Present report