Fanconi anemia differential diagnosis: Difference between revisions
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*Fanconi Anemia must be differentiated from other diseases that cause Pancytopenia, Congenital anomalies, and associated with malignancy such as Aplastic Anemia, Rare chromosomal breakage syndrome and inherited bone marrow failure. | *Fanconi Anemia must be differentiated from other diseases that cause Pancytopenia, Congenital anomalies, and associated with malignancy such as Aplastic Anemia, Rare chromosomal breakage syndrome and inherited bone marrow failure. | ||
*As Fanconi Anemia resembles with variety of other diseases that causes pancytopenia | *As Fanconi Anemia resembles with variety of other diseases that causes pancytopenia. | ||
*Must be differentiated on basis on congenital anomalies and chromosomal breakage test. | *Must be differentiated on basis on congenital anomalies and chromosomal breakage test. | ||
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|+ | |+ | ||
|- style="background: #4479BA; color: #FFFFFF; text-align: center;" | |- style="background: #4479BA; color: #FFFFFF; text-align: center;" | ||
| colspan=" | | colspan="3" rowspan="2" |'''Clinical manifestations''' | ||
| rowspan="3" |Pathophysiology | |||
| colspan="1" rowspan=" | ! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Para-clinical findings | ||
! rowspan=" | | colspan="1" rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |'''Gold standard''' | ||
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Additional findings | |||
|- | |- | ||
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab Findings | |||
! | ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging | ||
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Histopathology | |||
|- | |- | ||
|Disease | |||
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptom | |||
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physical exam | |||
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Blood profile | |||
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptom | ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Anamalies | ||
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physical exam | |||
! style="background: #4479BA; color: #FFFFFF; text-align: center;" | | |||
! style="background: #4479BA; color: #FFFFFF; text-align: center;" | | |||
|- | |- | ||
|Fanconi Anemia | |||
|Short stature, delicate features, upper limbs absent or hypoplastic thumbs, supernumerary, bifid clinodactyly | |Short stature, delicate features, upper limbs absent or hypoplastic thumbs, supernumerary, bifid clinodactyly | ||
infection, petechia, pallor | |||
|Skin – Generalized hyperpigmentation; hypopigmented areas; large freckles, café-au-lait spots | |Skin – Generalized hyperpigmentation; hypopigmented areas; large freckles, café-au-lait spots | ||
Head – Microcephaly or hydrocephaly; birdlike face, mid-face hypoplasia, Sprengel's deformity of neck, | |||
Eyes- Microphthalmia, ptosis, epicanthal folds, strabismus | Eyes- Microphthalmia, ptosis, epicanthal folds, strabismus | ||
| | |Inherited defect in DNA Repair causes loss of HSC that leads | ||
to bone marrow failure. | |||
|Anemia | |||
normocellular or hypercellular bone marrow | |||
|Gastrointestinal Atresias, imperforate | |||
anus, TE fistula, malrotation, | |||
| | |||
|Gastrointestinal | |||
Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis | Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis | ||
| | | | ||
|FA gene sequencing | |FA gene | ||
sequencing | |||
|Incrreased chromosomal breakage in response to mitomycin C or diepoxybutane (quite sensitive but not entirely specific) | |Incrreased chromosomal breakage in response to mitomycin C or diepoxybutane (quite sensitive but not entirely specific) | ||
|- | |- | ||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Acquired Aplastic Anemia | | style="background: #DCDCDC; padding: 5px; text-align: center;" |Acquired Aplastic Anemia | ||
| style="background: #F5F5F5; padding: 5px;" |infections | | style="background: #F5F5F5; padding: 5px;" |infections mucosal hemorrhage menorrhagia | ||
| style="background: #F5F5F5; padding: 5px;" |especially pallor and petechiae. | | style="background: #F5F5F5; padding: 5px;" |especially pallor and petechiae. | ||
The liver, spleen, and lymph nodes are typically enlarged in AA, if its enlarged it may suggest alternative diagnosis | |||
| style="background: #F5F5F5; padding: 5px;" | | |No known causes 70% cases, known cases are caused | ||
| style="background: #F5F5F5; padding: 5px;" | | by drugs, virus, radiation | ||
| style="background: #F5F5F5; padding: 5px;" |Anemia | |||
normocellular or hypercellular bone marrow | |||
| style="background: #F5F5F5; padding: 5px;" |Gastrointestinal Atresias, imperforate | |||
anus, TE fistula, malrotation, | |||
Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis | |||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" |hypocellular bone | ||
marrow | |||
| style="background: #F5F5F5; padding: 5px;" |rapid onset | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
|- | |- | ||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Paroxysmal nocturnal hemoglobinuria (PNH) | |||
| style="background: #F5F5F5; padding: 5px;" |Fatigue | | style="background: #F5F5F5; padding: 5px;" |Fatigue | ||
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●Hemoglobinuria | ●Hemoglobinuria | ||
Abdominal pain | |||
●Bone marrow suppression | ●Bone marrow suppression | ||
●Erectile dysfunction | ●Erectile dysfunction | ||
Chest pain | |||
●Thrombosis | ●Thrombosis | ||
Line 124: | Line 92: | ||
●Renal insufficiency | ●Renal insufficiency | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| | |Acquired mutation in PIGA gene --> problem in synthesis of | ||
DGI ---> complement mediated Intravascular hemolysis | |||
| style="background: #F5F5F5; padding: 5px;" |Anemia | | style="background: #F5F5F5; padding: 5px;" |Anemia | ||
normocellular or hypercellular bone marrow | |||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| style="background: #F5F5F5; padding: 5px;" |●Hypo/Hyper | |||
/Normo | |||
cellular, | |||
| style="background: #F5F5F5; padding: 5px;" |Flow cytometry | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
|- | |- | ||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Other inherited bone marrow failure syndromes | | style="background: #DCDCDC; padding: 5px; text-align: center;" |Other inherited bone marrow failure syndromes | ||
(Dyskeratosis congenita and other short telomere syndromes) | (Dyskeratosis congenita and other short telomere syndromes) | ||
| style="background: #F5F5F5; padding: 5px;" |'''Bone marrow failure''' | | style="background: #F5F5F5; padding: 5px;" |'''Bone marrow failure''' | ||
Classic mucocutaneous and additional dermatologic findings | Classic mucocutaneous and additional dermatologic findings | ||
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•Microcephaly | •Microcephaly | ||
Pulmonary disease (pulmonary fibrosis) | |||
●Endocrine/Growth/Urologic | ●Endocrine/Growth/Urologic | ||
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●Cancer | ●Cancer | ||
| | |(DC) and telomere related | ||
disorders, mutations in genes that maintain telomere length in | |||
rapidly dividing cells that lead | |||
to premature cell death, senescence, or genomic instability, which in turn results | |||
in impaired function and cellular homeostasis in many organs and tissues. | |||
| style="background: #F5F5F5; padding: 5px;" |Reticular dysgenesis | |||
| style="background: #F5F5F5; padding: 5px;" | | |||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" |Flow cytometry | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | - chromosomal breakage test. | ||
|- | |- | ||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Drug-induced or infection-associated pancytopenia | | style="background: #DCDCDC; padding: 5px; text-align: center;" |Drug-induced or infection-associated pancytopenia | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| | |||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
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| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
|- | |- | ||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Rare syndromes, | |||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Rare | Nijmegen breakage | ||
syndrome (''NBS''), | |||
Bloom syndrome | |||
(''BLM''), ataxia | |||
telangiectasia | |||
(''ATM''), LIG4 | |||
syndrome (''LIG4''), | |||
NHEJ1 deficiency | |||
(''NHEJ1''), Seckel syndrome ''(ATR)'', | |||
'' ''cohesinopathies | |||
Roberts | |||
syndrome (''ESCO2'') | |||
Warsaw | |||
breakage syndrome (''DDX11''). | |||
| style="background: #F5F5F5; padding: 5px;" |microcephaly, short stature increased | |||
malignancy | |||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
|NBS: chromosomal instability disorder caused by mutations in the nibrin ''(NBN)'' gene, | |||
DNA breaks are not efficiently repaired in the absence of nibrin, | |||
oxidative/alkylating stress damages the cells | |||
| style="background: #F5F5F5; padding: 5px;" |no specific findings | |||
| style="background: #F5F5F5; padding: 5px;" |Gastrointestinal Atresias, imperforate | |||
anus, TE fistula, malrotation, | |||
Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis | |||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" |abnormal chromosomal breakage test | ||
| style="background: #F5F5F5; padding: 5px;" |No bone | |||
marrow | |||
| style="background: #F5F5F5; padding: 5px;" | | failure | ||
|- | |- | ||
| style="background: #DCDCDC; padding: 5px; text-align: center;" |De novo myelodysplastic syndrome (MDS) | |||
| style="background: #F5F5F5; padding: 5px;" |MDS can arise de novo or secondary to another bone marrow disorder; | | style="background: #F5F5F5; padding: 5px;" |MDS can arise de novo or secondary to another bone marrow disorder; | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| | |||
| style="background: #F5F5F5; padding: 5px;" |bone marrow failure | |||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" |Positive | ||
chromosomal breakage tests | |||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" | | ||
| style="background: #F5F5F5; padding: 5px;" | | | style="background: #F5F5F5; padding: 5px;" |Negitive | ||
chromosomal breakage tests | |||
|} | |} | ||
Revision as of 16:59, 24 June 2018
Fanconi anemia Microchapters |
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Fanconi anemia differential diagnosis On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Fanconi Anemia must be differentiated from Aplastic Anemia, Paraoxysomal Nocturnal Hemoglobinuria, and Chromosomal breakage syndrome and Hereditary Bone marrow failure syndrome (Dyskeratosis congenita and other short telomere syndromes).
Differentiating X from other Diseases
- Fanconi Anemia must be differentiated from other diseases that cause Pancytopenia, Congenital anomalies, and associated with malignancy such as Aplastic Anemia, Rare chromosomal breakage syndrome and inherited bone marrow failure.
- As Fanconi Anemia resembles with variety of other diseases that causes pancytopenia.
- Must be differentiated on basis on congenital anomalies and chromosomal breakage test.
Preferred Table
Clinical manifestations | Pathophysiology | Para-clinical findings | Gold standard | Additional findings | ||||
---|---|---|---|---|---|---|---|---|
Lab Findings | Imaging | Histopathology | ||||||
Disease | Symptom | Physical exam | Blood profile | Anamalies | ||||
Fanconi Anemia | Short stature, delicate features, upper limbs absent or hypoplastic thumbs, supernumerary, bifid clinodactyly
infection, petechia, pallor |
Skin – Generalized hyperpigmentation; hypopigmented areas; large freckles, café-au-lait spots
Head – Microcephaly or hydrocephaly; birdlike face, mid-face hypoplasia, Sprengel's deformity of neck, Eyes- Microphthalmia, ptosis, epicanthal folds, strabismus |
Inherited defect in DNA Repair causes loss of HSC that leads
to bone marrow failure. |
Anemia
normocellular or hypercellular bone marrow |
Gastrointestinal Atresias, imperforate
anus, TE fistula, malrotation, Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis |
FA gene
sequencing |
Incrreased chromosomal breakage in response to mitomycin C or diepoxybutane (quite sensitive but not entirely specific) | |
Acquired Aplastic Anemia | infections mucosal hemorrhage menorrhagia | especially pallor and petechiae.
The liver, spleen, and lymph nodes are typically enlarged in AA, if its enlarged it may suggest alternative diagnosis |
No known causes 70% cases, known cases are caused
by drugs, virus, radiation |
Anemia
normocellular or hypercellular bone marrow |
Gastrointestinal Atresias, imperforate
anus, TE fistula, malrotation, Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis |
hypocellular bone
marrow |
rapid onset | |
Paroxysmal nocturnal hemoglobinuria (PNH) | Fatigue
●Dyspnea ●Hemoglobinuria Abdominal pain ●Bone marrow suppression ●Erectile dysfunction Chest pain ●Thrombosis ●Renal insufficiency |
Acquired mutation in PIGA gene --> problem in synthesis of
DGI ---> complement mediated Intravascular hemolysis |
Anemia
normocellular or hypercellular bone marrow |
●Hypo/Hyper
/Normo cellular, |
Flow cytometry | |||
Other inherited bone marrow failure syndromes
(Dyskeratosis congenita and other short telomere syndromes) |
Bone marrow failure
Classic mucocutaneous and additional dermatologic findings •Skin dyspigmentation •Nail irregularities •Leukoplakia •Premature graying/hair loss •Hyperhidrosis – 15 percent Ophthalmologic/Epiphora (excessive tearing/lacrimal duct stenosis) ●Neurologic/Cognitive •Developmental delay •Ataxia/cerebellar hypoplasia – approximately •Microcephaly Pulmonary disease (pulmonary fibrosis) ●Endocrine/Growth/Urologic features •Short stature •Intrauterine growth retardation •Hypogonadism/Undescended testes •Urethral stricture/phimosis •Osteoporosis and related complications |
Unlike Fanconi anemia, individuals with DC do not appear to have impaired fertility
●Dental manifestations (caries) ●Gastroenterologic/Hepatologic manifestations •Esophageal strictures •Liver disease (cirrhosis, fibrosis) or gastroenteropathy ●Cancer |
(DC) and telomere related
disorders, mutations in genes that maintain telomere length in rapidly dividing cells that lead to premature cell death, senescence, or genomic instability, which in turn results in impaired function and cellular homeostasis in many organs and tissues. |
Reticular dysgenesis | Flow cytometry | - chromosomal breakage test. | ||
Drug-induced or infection-associated pancytopenia | ||||||||
Rare syndromes,
Nijmegen breakage syndrome (NBS), Bloom syndrome (BLM), ataxia telangiectasia (ATM), LIG4 syndrome (LIG4), NHEJ1 deficiency (NHEJ1), Seckel syndrome (ATR), cohesinopathies Roberts syndrome (ESCO2) Warsaw breakage syndrome (DDX11). |
microcephaly, short stature increased
malignancy |
NBS: chromosomal instability disorder caused by mutations in the nibrin (NBN) gene,
DNA breaks are not efficiently repaired in the absence of nibrin, oxidative/alkylating stress damages the cells |
no specific findings | Gastrointestinal Atresias, imperforate
anus, TE fistula, malrotation, Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis |
abnormal chromosomal breakage test | No bone
marrow failure | ||
De novo myelodysplastic syndrome (MDS) | MDS can arise de novo or secondary to another bone marrow disorder; | bone marrow failure | Positive
chromosomal breakage tests |
Negitive
chromosomal breakage tests |