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Corticosterone methyloxidase type 2 deficiency(FHHA1B)

MedGen UID:
483046
Concept ID:
C3463917
Disease or Syndrome
Synonyms: 18-OXIDASE DEFICIENCY; ALDOSTERONE DEFICIENCY DUE TO DEFICIENCY OF STEROID 18-OXIDASE; ALDOSTERONE DEFICIENCY II; CMO II DEFICIENCY; Corticosterone Methyloxidase Type II Deficiency; STEROID 18-OXIDASE DEFICIENCY
SNOMED CT: CMO II deficiency (47757001); Corticosterone methyl oxidase type II deficiency (47757001)
 
Gene (location): CYP11B2 (8q24.3)
 
Monarch Initiative: MONDO:0012524
OMIM®: 610600

Definition

CMO type II deficiency is an autosomal recessive disorder caused by a defect in the final biochemical step of aldosterone biosynthesis, the 18-hydroxylation of 18-hydroxycorticosterone (18-OHB) to aldosterone. This enzymatic defect results in decreased aldosterone and salt-wasting associated with an increased serum ratio of 18-OHB to aldosterone. In CMO II deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18-OHB. These patients have a low ratio of corticosterone to 18-OHB (Portrat-Doyen et al., 1998). The CYP11B2 gene product also catalyzes an earlier step in aldosterone biosynthesis: the 18-hydroxylation of corticosterone to 18-OHB. A defect in that enzymatic step results in CMO type I deficiency (204300), an allelic disorder with an overlapping phenotype but distinct biochemical features. In CMO I deficiency, aldosterone is undetectable, whereas its immediate precursor, 18-OHB, is low or normal (Portrat-Doyen et al., 1998). [from OMIM]

Additional description

From MedlinePlus Genetics
The hyponatremia, hyperkalemia, and metabolic acidosis associated with corticosterone methyloxidase deficiency can cause nausea, vomiting, dehydration, low blood pressure, extreme tiredness (fatigue), and muscle weakness. Affected infants often experience failure to thrive, which means they do not gain weight and grow at the expected rate. Severe cases of corticosterone methyloxidase deficiency can result in seizures and coma and can be life-threatening. However, affected individuals who survive infancy generally have a normal life expectancy, and the signs and symptoms of the disorder typically become milder or disappear by adulthood.

Corticosterone methyloxidase deficiency, also known as aldosterone synthase deficiency, is a disorder characterized by excessive amounts of sodium released in the urine (salt wasting), along with insufficient release of potassium in the urine, usually beginning in the first few weeks of life. This imbalance leads to low levels of sodium and high levels of potassium in the blood (hyponatremia and hyperkalemia, respectively). Individuals with corticosterone methyloxidase deficiency can also have high levels of acid in the blood (metabolic acidosis).  https://medlineplus.gov/genetics/condition/corticosterone-methyloxidase-deficiency

Clinical features

From HPO
Renal salt wasting
MedGen UID:
375868
Concept ID:
C1846347
Finding
A high concentration of one or more electrolytes in the urine in the presence of low serum concentrations of the electrolyte(s).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Orthostatic hypotension
MedGen UID:
43803
Concept ID:
C0020651
Disease or Syndrome
A form of hypotension characterized by a sudden fall in blood pressure that occurs when a person assumes a standing position.
Dehydration
MedGen UID:
8273
Concept ID:
C0011175
Disease or Syndrome
A condition resulting from the excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.
Hyperkalemia
MedGen UID:
5691
Concept ID:
C0020461
Finding
An abnormally increased potassium concentration in the blood.
Hyponatremia
MedGen UID:
6984
Concept ID:
C0020625
Finding
An abnormally decreased sodium concentration in the blood.
Increased circulating renin concentration
MedGen UID:
66818
Concept ID:
C0240783
Finding
An increased level of renin in the blood.
Decreased circulating aldosterone concentration
MedGen UID:
208996
Concept ID:
C0857899
Finding
Abnormally reduced levels of aldosterone.
Increased circulating corticosterone level
MedGen UID:
1694925
Concept ID:
C5139295
Finding
An abnormally elevated concentration of corticosterone in the blood.
Increased circulating 18-hydroxycortisone level
MedGen UID:
1706651
Concept ID:
C5209282
Finding
An abnormally elevated concentration of 18-Hydroxycorticosterone level in the blood circulation.

Recent clinical studies

Etiology

Kater CE, Biglieri EG, Rost CR, Schambelan M, Hirai J, Chang BC, Brust N
J Clin Endocrinol Metab 1985 Feb;60(2):225-8. doi: 10.1210/jcem-60-2-225. PMID: 2981240
Rösler A
J Clin Endocrinol Metab 1984 Oct;59(4):689-700. doi: 10.1210/jcem-59-4-689. PMID: 6384251

Diagnosis

Turan H, Dağdeviren Çakır A, Özer Y, Tarçın G, Özcabi B, Ceylaner S, Ercan O, Evliyaoğlu SO
J Clin Res Pediatr Endocrinol 2021 Jun 2;13(2):232-238. Epub 2020 Jun 16 doi: 10.4274/jcrpe.galenos.2020.2019.0216. PMID: 32539318Free PMC Article

Therapy

Santen RJ, Demers LM, Lynch J, Harvey H, Lipton A, Mulagha M, Hanagan J, Garber JE, Henderson IC, Navari RM
J Clin Endocrinol Metab 1991 Jul;73(1):99-106. doi: 10.1210/jcem-73-1-99. PMID: 1646219
de Jongh BM, Veldhuis JD, Drop SL, Nijenhuis LE, Dupont B
Tissue Antigens 1984 Jul;24(1):18-24. doi: 10.1111/j.1399-0039.1984.tb00392.x. PMID: 6592791

Clinical prediction guides

Portrat-Doyen S, Tourniaire J, Richard O, Mulatero P, Aupetit-Faisant B, Curnow KM, Pascoe L, Morel Y
J Clin Endocrinol Metab 1998 Nov;83(11):4156-61. doi: 10.1210/jcem.83.11.5258. PMID: 9814506
Santen RJ, Demers LM, Lynch J, Harvey H, Lipton A, Mulagha M, Hanagan J, Garber JE, Henderson IC, Navari RM
J Clin Endocrinol Metab 1991 Jul;73(1):99-106. doi: 10.1210/jcem-73-1-99. PMID: 1646219
Brautbar C, Theodor R, Sack J, Levene C, Dupont B, Levine LS, Sharon R, Smaller S, Cohen T, Rösler A
Tissue Antigens 1981 Feb;17(2):212-6. doi: 10.1111/j.1399-0039.1981.tb00685.x. PMID: 7233416

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