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Combined malonic and methylmalonic aciduria(CMAMMA)

MedGen UID:
481944
Concept ID:
C3280314
Disease or Syndrome
Synonyms: CMAMMA
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). [HPO:curators]
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: CMAMMA - combined malonic and methylmalonic aciduria (702365002); Combined malonic and methylmalonic aciduria (702365002)
 
Gene (location): ACSF3 (16q24.3)
OMIM®: 614265
Orphanet: ORPHA289504

Definition

Combined malonic and methylmalonic aciduria (CMAMMA) is a condition characterized by high levels of certain chemicals, known as malonic acid and methylmalonic acid, in the body. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine, although both are elevated.The signs and symptoms of CMAMMA can begin in childhood. In some children, the buildup of acids causes the blood to become too acidic (ketoacidosis), which can damage the body's tissues and organs. Other signs and symptoms may include involuntary muscle tensing (dystonia), weak muscle tone (hypotonia), developmental delay, an inability to grow and gain weight at the expected rate (failure to thrive), low blood sugar (hypoglycemia), and coma. Some affected children have an unusually small head size (microcephaly).Other people with CMAMMA do not develop signs and symptoms until adulthood. These individuals usually have neurological problems, such as seizures, loss of memory, a decline in thinking ability, or psychiatric diseases.
[from GHR]

Clinical features

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.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency of loose or watery bowel movements.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Ketoacidosis
MedGen UID:
67434
Concept ID:
C0220982
Pathologic Function
Acidosis resulting from accumulation of ketone bodies.
Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Finding
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Methylmalonic aciduria
MedGen UID:
343266
Concept ID:
C1855119
Disease or Syndrome
Increased concentration of methylmalonic acid in the urine.
Global developmental delay
MedGen UID:
892935
Concept ID:
C4020875
Pathologic Function
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Generalized clonic seizures
MedGen UID:
869081
Concept ID:
C4023499
Disease or Syndrome
Seizures with regularly repetitive myoclonus, involving the same muscle groups, at a frequency of about 2-3 c/sec.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCombined malonic and methylmalonic aciduria
Follow this link to review classifications for Combined malonic and methylmalonic aciduria in Orphanet.

Recent clinical studies

Etiology

Sloan JL, Johnston JJ, Manoli I, Chandler RJ, Krause C, Carrillo-Carrasco N, Chandrasekaran SD, Sysol JR, O'Brien K, Hauser NS, Sapp JC, Dorward HM, Huizing M; NIH Intramural Sequencing Center Group., Barshop BA, Berry SA, James PM, Champaigne NL, de Lonlay P, Valayannopoulos V, Geschwind MD, Gavrilov DK, Nyhan WL, Biesecker LG, Venditti CP
Nat Genet 2011 Aug 14;43(9):883-6. doi: 10.1038/ng.908. PMID: 21841779Free PMC Article

Diagnosis

Sloan JL, Johnston JJ, Manoli I, Chandler RJ, Krause C, Carrillo-Carrasco N, Chandrasekaran SD, Sysol JR, O'Brien K, Hauser NS, Sapp JC, Dorward HM, Huizing M; NIH Intramural Sequencing Center Group., Barshop BA, Berry SA, James PM, Champaigne NL, de Lonlay P, Valayannopoulos V, Geschwind MD, Gavrilov DK, Nyhan WL, Biesecker LG, Venditti CP
Nat Genet 2011 Aug 14;43(9):883-6. doi: 10.1038/ng.908. PMID: 21841779Free PMC Article

Prognosis

Sloan JL, Johnston JJ, Manoli I, Chandler RJ, Krause C, Carrillo-Carrasco N, Chandrasekaran SD, Sysol JR, O'Brien K, Hauser NS, Sapp JC, Dorward HM, Huizing M; NIH Intramural Sequencing Center Group., Barshop BA, Berry SA, James PM, Champaigne NL, de Lonlay P, Valayannopoulos V, Geschwind MD, Gavrilov DK, Nyhan WL, Biesecker LG, Venditti CP
Nat Genet 2011 Aug 14;43(9):883-6. doi: 10.1038/ng.908. PMID: 21841779Free PMC Article
Alfares A, Nunez LD, Al-Thihli K, Mitchell J, Melançon S, Anastasio N, Ha KC, Majewski J, Rosenblatt DS, Braverman N
J Med Genet 2011 Sep;48(9):602-5. Epub 2011 Jul 23 doi: 10.1136/jmedgenet-2011-100230. PMID: 21785126

Clinical prediction guides

Sloan JL, Johnston JJ, Manoli I, Chandler RJ, Krause C, Carrillo-Carrasco N, Chandrasekaran SD, Sysol JR, O'Brien K, Hauser NS, Sapp JC, Dorward HM, Huizing M; NIH Intramural Sequencing Center Group., Barshop BA, Berry SA, James PM, Champaigne NL, de Lonlay P, Valayannopoulos V, Geschwind MD, Gavrilov DK, Nyhan WL, Biesecker LG, Venditti CP
Nat Genet 2011 Aug 14;43(9):883-6. doi: 10.1038/ng.908. PMID: 21841779Free PMC Article
Alfares A, Nunez LD, Al-Thihli K, Mitchell J, Melançon S, Anastasio N, Ha KC, Majewski J, Rosenblatt DS, Braverman N
J Med Genet 2011 Sep;48(9):602-5. Epub 2011 Jul 23 doi: 10.1136/jmedgenet-2011-100230. PMID: 21785126
Gregg AR, Warman AW, Thorburn DR, O'Brien WE
J Inherit Metab Dis 1998 Jun;21(4):382-90. PMID: 9700595

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