Pearson syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: Sideroblastic anemia with marrow cell vacuolization and exocrine pancreatic dysfunction
Pearson marrow-pancreas syndrome [IBIS]
Number of Symptoms 76
OrphanetNr: 699
OMIM Id: 557000
ICD-10: D64.0
UMLs:
MeSH:
MedDRA: 10062941
Snomed: 237985009

Prevalence, inheritance and age of onset:

Prevalence: 60 cases [Orphanet]
Inheritance: Mitochondrial
7581370; 25691415 [IBIS]
Age of onset: Neonatal
Infancy
7581370; 25691415 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Constitutional neutropenia with extra-haematopoietic manifestations
 -Rare genetic disease
 -Rare immune disease
Constitutional sideroblastic anemia
 -Rare genetic disease
 -Rare hematologic disease
Metabolic disease with intestinal involvement
 -Rare gastroenterologic disease
 -Rare genetic disease
Mitochondrial disease with eye involvement
 -Rare eye disease
 -Rare genetic disease
Mitochondrial oxidative phosphorylation disorder due to a large-scale single deletion of mitochondrial DNA
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease
Syndrome with hypoparathyroidism
 -Rare endocrine disease
 -Rare genetic disease

Comment:

Pearson marrow-pancreas syndrome is a multisystem mitochondrial disorder due to mtDNA deletions or rearrangements characterized by bone marrow failure and pancreatic insufficiency. Children who survive the severe bone marrow dysfunction in childhood develop Kearns–Sayre syndrome later in life (PMID:25691415). Direct repeats (4-13 bp) were consistently present in the wild-type mtDNA at the boundaries of the deletions. Deletion-dimers, deletion-multimers or duplications were observed in association with deletions (PMID:7581370).

Symptom Information: Sort by abundance 

1
 (HPO:0002039) Anorexia Rare [IBIS] 5% (n=21) 7581370 IBIS 62 / 7739
2
 (HPO:0002028) Chronic diarrhea 25691415 IBIS 51 / 7739
3
 (HPO:0008872) Feeding difficulties in infancy Occasional [IBIS] 25% (n=4) 25691415 IBIS 153 / 7739
4
 (HPO:0002013) Vomiting Occasional [IBIS] 10% (n=21) 7581370 IBIS 191 / 7739
5
 (HPO:0012544) Elevated aldolase level 25691415 IBIS 1 / 7739
6
 (HPO:0003155) Elevated alkaline phosphatase 25691415 IBIS 52 / 7739
7
 (HPO:0000816) Abnormality of Krebs cycle metabolism 25691415 IBIS 3 / 7739
8
 (HPO:0003128) Lactic acidosis Very frequent [IBIS] 100% (n=4) 25691415 IBIS 116 / 7739
9
 (HPO:0003648) Lacticaciduria 25691415 IBIS 6 / 7739
10
 (HPO:0001942) Metabolic acidosis Occasional [IBIS] 25% (n=4) 25691415 IBIS 81 / 7739
11
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 25691415 IBIS 492 / 7739
12
 (HPO:0001508) Failure to thrive Very frequent [IBIS] 100% (n=4) 25691415 IBIS 454 / 7739
13
 (HPO:0012145) Abnormality of multiple cell lineages in the bone marrow Very frequent [IBIS] 100% (n=4) 25691415 IBIS 11 / 7739
14
 (HPO:0005528) Bone marrow hypocellularity Frequent [IBIS] 75% (n=4) 25691415 IBIS 31 / 7739
15
 (HPO:0001980) Megaloblastic bone marrow 25691415 IBIS 5 / 7739
16
 (HPO:0001876) Pancytopenia Frequent [IBIS] 50% (n=4) 25691415 IBIS 89 / 7739
17
 (HPO:0002901) Hypocalcemia Occasional [IBIS] 25% (n=4) 25691415 IBIS 56 / 7739
18
 (HPO:0003076) Glycosuria 25691415 IBIS 32 / 7739
19
 (HPO:0003572) Low plasma citrulline Frequent [IBIS] 75% (n=4) 25691415 IBIS 7 / 7739
20
 (HPO:0005961) Hypoargininemia Occasional [IBIS] 25% (n=4) 25691415 IBIS 7 / 7739
21
 (HPO:0012025) Abnormality of ornithine metabolism Occasional [IBIS] 25% (n=4) 25691415 IBIS 1 / 7739
22
 (HPO:0003112) Abnormality of serum amino acid levels 25691415 IBIS 2 / 7739
23
 (HPO:0003355) Aminoaciduria 25691415 IBIS 65 / 7739
24
 (HPO:0003344) 3-Methylglutaric aciduria 1447663 IBIS 6 / 7739
25
 (HPO:0003161) 4-Hydroxyphenylpyruvic aciduria 25691415 IBIS 4 / 7739
26
 (HPO:0003287) Abnormality of mitochondrial metabolism 25691415 IBIS 12 / 7739
27
 (HPO:0011902) Abnormal hemoglobin Very frequent [Orphanet] 25691415 IBIS 18 / 7739
28
 (HPO:0001903) Anemia Frequent [IBIS] Very frequent [Orphanet] 75% (n=4) 25691415 IBIS 289 / 7739
29
 (HPO:0001972) Macrocytic anemia 25691415 IBIS 26 / 7739
30
 (HPO:0001924) Sideroblastic anemia 25691415 IBIS 12 / 7739
31
 (HPO:0011273) Anisocytosis Occasional [IBIS] 25% (n=4) 25691415 IBIS 8 / 7739
32
 (HPO:0005518) Erythrocyte macrocytosis 25691415 IBIS 13 / 7739
33
 (HPO:0100651) Type I diabetes mellitus Very frequent [Orphanet] 22424738 IBIS 44 / 7739
34
 (HPO:0002719) Recurrent infections Frequent [IBIS] 75% (n=4) 25691415 IBIS 107 / 7739
35
 (HPO:0001875) Neutropenia Occasional [IBIS] 25% (n=4) 25691415 IBIS 83 / 7739
36
 (HPO:0001397) Hepatic steatosis 25691415 IBIS 75 / 7739
37
 (HPO:0001992) Organic aciduria Very frequent [Orphanet] 25691415 IBIS 28 / 7739
38
 (HPO:0001252) Muscular hypotonia Frequent [IBIS] Very frequent [Orphanet] 50% (n=4) 25691415 IBIS 990 / 7739
39
 (HPO:0001281) Tetany Occasional [IBIS] 25% (n=4) 25691415 IBIS 20 / 7739
40
 (HPO:0001254) Lethargy Occasional [IBIS] 25% (n=4) 25691415 IBIS 104 / 7739
41
 (HPO:0009886) Trichorrhexis nodosa 25691415 IBIS 12 / 7739
42
 (HPO:0001596) Alopecia 25691415 IBIS 162 / 7739
43
 (HPO:0002024) Malabsorption Very frequent [Orphanet] 25691415 IBIS 142 / 7739
44
 (HPO:0001396) Cholestasis Occasional [IBIS] 25% (n=4) 25691415 IBIS 136 / 7739
45
 (HPO:0002910) Elevated hepatic transaminases 25691415 IBIS 158 / 7739
46
 (HPO:0001395) Hepatic fibrosis 25691415 IBIS 67 / 7739
47
 (HPO:0200119) Acute hepatitis 25691415 IBIS 2 / 7739
48
 (HPO:0002240) Hepatomegaly 25691415 IBIS 467 / 7739
49
 (HPO:0012090) Abnormality of pancreas morphology Very frequent [Orphanet] 25691415 IBIS 31 / 7739
50
 (HPO:0001738) Exocrine pancreatic insufficiency Very frequent [IBIS] 100% (n=4) 25691415 IBIS 23 / 7739
51
 (HPO:0001737) Pancreatic cysts Occasional [IBIS] 25% (n=4) 25691415 IBIS 15 / 7739
52
 (HPO:0100732) Pancreatic fibrosis 25691415 IBIS 12 / 7739
53
 (HPO:0001735) Acute pancreatitis Occasional [IBIS] 25% (n=4) 25691415 IBIS 6 / 7739
54
 (HPO:0100027) Recurrent pancreatitis Occasional [IBIS] 25% (n=4) 25691415 IBIS 3 / 7739
55
 (HPO:0012091) Abnormality of pancreas physiology Very frequent [Orphanet] 25691415 IBIS 3 / 7739
56
 (HPO:0012093) Abnormality of endocrine pancreas physiology Occasional [IBIS] 25% (n=4) 25691415 IBIS 4 / 7739
57
 (HPO:0000846) Adrenal insufficiency 22424738 IBIS 24 / 7739
58
 (HPO:0000818) Abnormality of the endocrine system 22424738 IBIS 26 / 7739
59
 (HPO:0001000) Abnormality of skin pigmentation Very frequent [Orphanet] 25691415 IBIS 105 / 7739
60
 (HPO:0000980) Pallor 25691415 IBIS 52 / 7739
61
 (HPO:0012573) Global proximal tubulopathy Very frequent [IBIS] 100% (n=4) 25691415 IBIS 4 / 7739
62
 (HPO:0001994) Renal Fanconi syndrome Very frequent [IBIS] 100% (n=4) 25691415 IBIS 12 / 7739
63
 (HPO:0000124) Renal tubular dysfunction Very frequent [IBIS] 100% (n=4) 25691415 IBIS 46 / 7739
64
 (HPO:0000093) Proteinuria 25691415 IBIS 169 / 7739
65
 (HPO:0001873) Thrombocytopenia Frequent [IBIS] 50% (n=4) 25691415 IBIS 224 / 7739
66
 (HPO:0002919) Ketonuria 25691415 IBIS 18 / 7739
67
 (HPO:0009025) Increased connective tissue 25691415 IBIS 11 / 7739
68
 (HPO:0003689) Multiple mitochondrial DNA deletions 25691415 IBIS 12 / 7739
69
 (MedDRA:10048804) Kearns-Sayre syndrome 25691415 IBIS 1 / 7739
70
 (MedDRA:10028154) Multi-organ failure 22424738 IBIS 3 / 7739
71
 (OMIM) 3-hydroxyisobutyric aciduria 25691415 IBIS 2 / 7739
72
 (OMIM) Exocrine pancreatic dysfunction 25691415 IBIS 1 / 7739
73
 (OMIM) Heteroplasmic mtDNA deletion 25691415 IBIS 2 / 7739
74
 (OMIM) Increased ketone body or lactate/pyruvate plasma ratios 25691415 IBIS 1 / 7739
75
 (OMIM) Mitochondrial deletions 25691415 IBIS 1 / 7739
76
 (OMIM) Vacuolization of marrow precursors 7581370 IBIS 1 / 7739

Associated genes:

mtDNA deletions or rearrangements;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information: