Red cell disorders

Gene: SLC4A1

Green List (high evidence)

Cryohydrocytosis
>10 families with monoallelic variants (majority missense)
Cryohydrocytosis is characterised by a mild stomatocytic haemolytic state with hyperbilirubinemia. Individuals display an increase in red cell membrane permeability to sodium and potassium in the cold. Patients present with fatigue, splenomegaly, mild anaemia, and pseudohyperkalaemia due to a potassium leak from the RBCs.
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Distal renal tubular acidosis 4 with haemolytic anaemia
>10 families reported with biallelic variants (deletion, missense)
Distal renal tubular acidosis 4 with haemolytic anaemia is characterised by haemolytic anaemia, and abnormal red cell properties (microcytosis, reticulocytosis). Other features include, height and weight less than the third percentile, lethargy, pallor, hyperchloremic metabolic acidosis, nephrocalcinosis, isothenuria, rachitic bone changes and hepatosplenomegaly.
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Ovalocytosis, SA type
>10 families reported with monoallelic variants *founder variant SLC4A1delta27 (27-bp deletion) in Southeast Asian population
Ovalocytosis in characterised by varying degrees of haemolytic anaemia and abnormal red cell properties (stomatocytic, ovalocytic, rigid and resistant to malarial parasite invasion). Other features include intermittent jaundice and abdominal pain due to pigment gall stones and enlarged spleen.
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Spherocytosis, type 4
>10 families reported with mono-allelic variants (missense, duplications, deletions)
Spherocytosis is characterised by the presence sphere-shaped erythrocytes (spherocytes) with increased osmotic fragility in peripheral smears with varying degrees of haemolytic anaemia, splenomegaly and jaundice (Hyperbilirubinemia). These characteristics can commonly lead to aplastic crisis, haemolytic episodes and the need for a splenectomy.
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Green- all phenotypes

Created: 14 Sep 2021, 1:21 a.m. | Last Modified: 14 Sep 2021, 1:21 a.m.

Panel Version: 0.128

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Cryohydrocytosis MIM# 185020; Distal renal tubular acidosis 4 with haemolytic anaemia MIM# 611590; Ovalocytosis, SA type MIM# 166900; Spherocytosis, type 4 MIM# 612653

Publications

• 16227998
• 15211439
• 10926824
• 7949112
• 16392641
• 8640229
• 16227998
• 8640229
• 16227998