Fatal infantile lactic acidosis with methylmalonic aciduria

General Information (adopted from Orphanet):

Synonyms, Signs: MTDPS9
LACTIC ACIDOSIS, FATAL INFANTILE, FORMERLY
Number of Symptoms 37
OrphanetNr: 17
OMIM Id: 245400
ICD-10: E87.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

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

Symptom Information: Sort by abundance 

1
 (HPO:0008335) Renal aminoaciduria 1 / 7739
2
 (HPO:0012120) Methylmalonic aciduria 20 / 7739
3
 (HPO:0000365) Hearing impairment rare [HPO:skoehler] 539 / 7739
4
 (HPO:0001298) Encephalopathy 72 / 7739
5
 (HPO:0001250) Seizures 1245 / 7739
6
 (HPO:0010864) Intellectual disability, severe 120 / 7739
7
 (HPO:0001251) Ataxia 413 / 7739
8
 (HPO:0002317) Unsteady gait 45 / 7739
9
 (HPO:0001263) Global developmental delay 853 / 7739
10
 (HPO:0002275) Poor motor coordination 6 / 7739
11
 (HPO:0011968) Feeding difficulties 240 / 7739
12
 (HPO:0001508) Failure to thrive 454 / 7739
13
 (HPO:0001510) Growth delay 295 / 7739
14
 (HPO:0000975) Hyperhidrosis 64 / 7739
15
 (HPO:0000951) Abnormality of the skin 147 / 7739
16
 (HPO:0001943) Hypoglycemia 131 / 7739
17
 (HPO:0002148) Hypophosphatemia 43 / 7739
18
 (HPO:0003128) Lactic acidosis 116 / 7739
19
 (HPO:0005941) Intermittent hyperpnea at rest 1 / 7739
20
 (HPO:0002093) Respiratory insufficiency 410 / 7739
21
 (HPO:0002878) Respiratory failure 57 / 7739
22
 (HPO:0003202) Skeletal muscle atrophy 281 / 7739
23
 (HPO:0001252) Muscular hypotonia 990 / 7739
24
 (HPO:0003200) Ragged-red muscle fibers 37 / 7739
25
 (OMIM) Inability to sit or hold head up 1 / 7739
26
 (OMIM) Delayed psychomotor development, severe 14 / 7739
27
 (HPO:0002059) Cerebral atrophy 171 / 7739
28
 (OMIM) Decreased activity and protein levels of respiratory chain complexes I, II, III, and IV 1 / 7739
29
 (HPO:0003812) Phenotypic variability 129 / 7739
30
 (OMIM) Increased lactate in spinal fluid 1 / 7739
31
 (OMIM) Hypotonia, axial, severe 1 / 7739
32
 (OMIM) Widening of the ventricles 1 / 7739
33
 (HPO:0003593) Infantile onset 249 / 7739
34
 (OMIM) Cox-negative fibers seen on muscle biopsy 1 / 7739
35
 (MedDRA:10059396) Mitochondrial DNA depletion 5 / 7739
36
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
37
 (OMIM) Brain MRI shows lesions in the basal ganglia 2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Mitochondrial DNA depletion syndrome-9 is a severe autosomal recessive disorder characterized by infantile onset of hypotonia, lactic acidosis, severe psychomotor retardation, progressive neurologic deterioration, and excretion of methylmalonic acid. Some patients die in early infancy (summary by Rouzier ...
Clinical Description OMIM - Early Descriptions

Erickson (1965) reported a mentally retarded brother and sister with familial infantile lactic acidosis. They had relatives who died in infancy, perhaps of the same condition. The diagnosis was suggested by discrepancy between ...
Molecular genetics OMIM In a consanguineous family of Pakistani origin with autosomal recessive fatal infantile lactic acidosis, Ostergaard et al. (2007) found a combined respiratory chain enzyme deficiency associated with mitochondrial DNA depletion. To identify the disease-causing gene, they performed single-nucleotide ...