Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

General Information (adopted from Orphanet):

Synonyms, Signs: MTDPS5
MITOCHONDRIAL DNA DEPLETION SYNDROME, ENCEPHALOMYOPATHIC FORM, WITH OR WITHOUT METHYLMALONIC ACIDURIA, AUTOSOMAL RECESSIVE, SUCLA2-RELATED
mtDNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria
Booth-Haworth-Dilling syndrome
Mitochondrial encephalomyopathy - aminoacidopathy
Number of Symptoms 66
OrphanetNr: 1933
OMIM Id: 612073
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 2 cases [Orphanet]
Inheritance: Mitochondrial inheritance
[Orphanet]
Age of onset: Neonatal
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial DNA depletion syndrome, encephalomyopathic form
 -Rare developmental defect during embryogenesis
 -Rare eye disease
 -Rare gastroenterologic disease
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0003355) Aminoaciduria 65 / 7739
2
(HPO:0012120) Methylmalonic aciduria 20 / 7739
3
(HPO:0000252) Microcephaly Very frequent [Orphanet] 832 / 7739
4
(HPO:0001349) Facial diplegia 16 / 7739
5
(HPO:0000508) Ptosis Very frequent [Orphanet] 459 / 7739
6
(HPO:0000486) Strabismus 576 / 7739
7
(HPO:0000505) Visual impairment Very frequent [Orphanet] 297 / 7739
8
(HPO:0000649) Abnormality of visual evoked potentials Very frequent [Orphanet] 34 / 7739
9
(HPO:0000602) Ophthalmoplegia 56 / 7739
10
(HPO:0000512) Abnormal electroretinogram Very frequent [Orphanet] 61 / 7739
11
(HPO:0000407) Sensorineural hearing impairment 524 / 7739
12
(HPO:0000365) Hearing impairment Very frequent [Orphanet] 539 / 7739
13
(HPO:0001257) Spasticity 251 / 7739
14
(HPO:0002540) Inability to walk 19 / 7739
15
(HPO:0001249) Intellectual disability 1089 / 7739
16
(HPO:0002066) Gait ataxia Very frequent [Orphanet] 327 / 7739
17
(HPO:0002194) Delayed gross motor development 37 / 7739
18
(HPO:0002448) Progressive encephalopathy 6 / 7739
19
(HPO:0003134) Abnormality of peripheral nerve conduction Very frequent [Orphanet] 38 / 7739
20
(HPO:0001332) Dystonia 197 / 7739
21
(HPO:0001315) Reduced tendon reflexes Very frequent [Orphanet] 160 / 7739
22
(HPO:0008945) Loss of ability to walk in early childhood 2 / 7739
23
(HPO:0001250) Seizures Very frequent [Orphanet] 1245 / 7739
24
(HPO:0006887) Intellectual disability, progressive 68 / 7739
25
(HPO:0000708) Behavioral abnormality Very frequent [Orphanet] 212 / 7739
26
(HPO:0001263) Global developmental delay 853 / 7739
27
(HPO:0002305) Athetosis 31 / 7739
28
(HPO:0009830) Peripheral neuropathy 206 / 7739
29
(HPO:0001265) Hyporeflexia 208 / 7739
30
(HPO:0000737) Irritability 93 / 7739
31
(HPO:0002514) Cerebral calcification Very frequent [Orphanet] 89 / 7739
32
(HPO:0011968) Feeding difficulties 240 / 7739
33
(HPO:0008872) Feeding difficulties in infancy 153 / 7739
34
(HPO:0001508) Failure to thrive 454 / 7739
35
(HPO:0004322) Short stature Very frequent [Orphanet] 1232 / 7739
36
(HPO:0004326) Cachexia Very frequent [Orphanet] 71 / 7739
37
(HPO:0011362) Abnormal hair quantity Very frequent [Orphanet] 92 / 7739
38
(HPO:0002912) Methylmalonic acidemia 14 / 7739
39
(HPO:0004337) Abnormality of amino acid metabolism Very frequent [Orphanet] 45 / 7739
40
(HPO:0003128) Lactic acidosis 116 / 7739
41
(HPO:0008972) Decreased activity of mitochondrial respiratory chain 34 / 7739
42
(HPO:0003236) Elevated serum creatine phosphokinase 214 / 7739
43
(HPO:0002747) Respiratory insufficiency due to muscle weakness 48 / 7739
44
(HPO:0003202) Skeletal muscle atrophy Very frequent [Orphanet] 281 / 7739
45
(HPO:0001324) Muscle weakness 859 / 7739
46
(HPO:0001252) Muscular hypotonia 990 / 7739
47
(HPO:0010547) Muscle flaccidity 466 / 7739
48
(HPO:0008947) Infantile muscular hypotonia 482 / 7739
49
(HPO:0000007) Autosomal recessive inheritance 2538 / 7739
50
(OMIM) Hyperkinetic movements 4 / 7739
51
(OMIM) Increased urinary carnitine esters 1 / 7739
52
(OMIM) Methylglutaconic aciduria, mild 1 / 7739
53
(OMIM) Aminoaciduria, intermittent 1 / 7739
54
(HPO:0030089) Abnormal muscle fiber protein expression Very frequent [Orphanet] 64 / 7739
55
(HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
56
(OMIM) Imaging shows signal abnormalities in basal ganglia 1 / 7739
57
(OMIM) Skeletal muscle tissue shows depletion of mitochondrial DNA (mtDNA) 1 / 7739
58
(OMIM) Methylmalonic aciduria, mild 2 / 7739
59
(OMIM) Crying, inconsolable 1 / 7739
60
(OMIM) Increased serum and CSF lactate 7 / 7739
61
(HPO:0003593) Infantile onset 249 / 7739
62
(OMIM) Psychomotor delay, severe 3 / 7739
63
(HPO:0002119) Ventriculomegaly Very frequent [Orphanet] 253 / 7739
64
(HPO:0002134) Abnormality of the basal ganglia 13 / 7739
65
(HPO:0002059) Cerebral atrophy 171 / 7739
66
(OMIM) Axonal and demyelinating peripheral neuropathy (in some patients) 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Mitochondrial DNA depletion syndrome-5 is an autosomal recessive disorder characterized by infantile onset of hypotonia, progressive neurologic deterioration, a hyperkinetic-dystonic movement disorder, external ophthalmoplegia, deafness, and variable renal tubular dysfunction. Laboratory studies often show mild methylmalonic aciduria (Carrozzo ...
Clinical Description OMIM Elpeleg et al. (2005) reported a small Muslim pedigree with an autosomal recessive encephalomyopathy associated with mtDNA depletion. The proband showed irritability and inconsolable crying in early infancy. She had severely delayed psychomotor development with marked muscle hypotonia, ...
Molecular genetics OMIM Elpeleg et al. (2005) identified a homozygous mutation in the SUCLA2 gene (603921.0001) in 2 first cousins from a consanguineous Muslim family with encephalomyopathy and mitochondrial DNA depletion syndrome-5. Urinary organic acid profiles were not reported in the ...
Population genetics OMIM Ostergaard et al. (2007) estimated the incidence of the encephalomyopathic form of mtDNA depletion syndrome with methylmalonic aciduria in the Faroe Islands to be 1 in 1,700.

Carrozzo et al. (2007) estimated the carrier and disease ...

Diagnosis GeneReviews SUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome is suspected in children with the following clinical findings [Elpeleg et al 2005, Carrozzo et al 2007, Ostergaard et al 2007b]:...
Clinical Description GeneReviews Pregnancy and birth are mostly unremarkable. Dysmaturity (relative absence of subcutaneous fat; wrinkling of the skin; prominent fingernails and toenails; and meconium staining of the skin and placental membranes, often associated with postmaturity or placental insufficiency) was reported in a few infants. With a few exceptions, birth weight and birth length were within the normal range. ...
Differential Diagnosis GeneReviews Mitochondrial DNA depletion syndrome, characterized by a reduction in mtDNA copy number, has been associated with mutations in eight nuclear genes: POLG, TK2, DGUOK, SUCLA2, SUCLG1, PEO1, MPV17, and RRM2B. The gene products are either involved in mtDNA replication or in regulation of the mitochondrial deoxyribonucleoside triphosphate (dNTP) pools needed for mtDNA replication. Inheritance for all the mtDNA depletion syndromes is autosomal recessive. ...
Management GeneReviews To establish the extent of disease in an individual diagnosed with SUCLA2-related mitochondrial DNA depletion syndrome, encephalomyopathic form, with mild methylmalonic aciduria, the following evaluations may be performed:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....