Table 3 IMDs associated with megaloblastic anemia
From: Blood cytopenias as manifestations of inherited metabolic diseases: a narrative review
Clinical signs | Biological signs | Gene (protein) | Specific biological sign | |
|---|---|---|---|---|
Impaired cobalamin absorption | ||||
Imerslund-Gräsbeck | Impaired absorption of B12 | Proteinuria Low plasmatic cobalamin | CUBN (cubulin) or AMN (amnionless) | ↘ plasmatic cobalamin |
Transcobalamin II deficiency | TCN2 (transcobalamin 2) | ↘ plasmatic cobalamin | ||
Impaired cobalamin metabolism | ||||
MMA | Developmental delay, progressive renal failure (tubulointerstitial nephritis), metabolic strokes, optic nerve atrophy | Metabolic acidosis, ketosis, hypoglycemia, hyperammonemia, neutropenia | Urinary organic acids: ↗ methylmalonic acid ↗ methylcitrate | |
MUT deficiency | MUT (methylmalonyl-CoA mutase) | |||
cblA type | MMAA (MMA type A protein) | |||
cblB type | MMAB (cobalamin adenosyltransferase) | |||
cblC type | MMACHC (MMA and homocystinuria type C protein) | |||
cblD type | MMADHC (MMA and homocystinuria type D protein) | |||
cblF type | LMRBD1 (Lysosomal cobalamin transport escort protein LMBD1) | |||
PA | Same as MMA + cardiomyopathy (9–23% of patients) | Same as MMA | PCCA (Propionyl-CoA Carboxylase Subunit Alpha) or PCCB (Propionyl-CoA Carboxylase Subunit Bêta) | Urinary organic acids: N methylmalonic acid↗ methylcitrate |
Methionine synthase reductase deficiency (cblE type) | Severe neonatal form: seizures, encephalopathy, hypotonia Adult attenuated form: psychiatric symptoms, acute neurological changes | MTRR (Methionine synthase reductase) | ↗ homocysteinemia and ↘ methioninemia | |
Methionine synthase deficiency (cblG) | MTR (5-Methyltetrahydrofolate-Homocysteine Methyltransferase) | |||
Impaired folate metabolism | ||||
MTHFD1 deficiency | Severe combined immunodeficiency with infections (repeated or opportunistic) and autoimmunity | MTHFD1 (methylenetetrahydrofolate dehydrogenase 1) | ↗homocysteine N methylmalonic acid, N methionine, N cobalamin, N folate | |
DHFR deficiency | DHFR (dihydrofolate reductase) | N total serum folate, N homocysteine, ↘ specific red blood cell folate levels ↘ CSF 5-methyl-tetrahydrofolate | ||
Formiminotransferase-cyclodeaminase deficiency | FTCD (Formiminotransferase-cyclodeaminase) | ↗ plasma and urine formiminoglutamic acid | ||
Impaired B1 metabolism | ||||
TRMA | Triad: megaloblastic anemia improving with B1 supplementation, diabetes mellitus, and deafness | SCLC19A2 (SCLC19A2) | ||