METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblC TYPE

Question 1

What is  METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblC TYPE?

Accepted Answer

rare (1:100.000, >550 cases)
autosomal recessive
mutation in the MMACHC gene
Methylmalonic aciduria and homocystinuria, cblC type is the most common inborn error of vitamin B(12) (cobalamin) metabolism [Lerner-Ellis JP 2006, De Simone L 2018].
partial CblC-type MMA can onset with severe metabolic aHUS [Chen M et al. 2017]

Question 2

Gibt es eine deutsche Bezeichnung?

Accepted Answer

Methylmalonazidämie mit Homocystinurie Typ cbl C

Question 3

What is the link to OMIM ?

Accepted Answer

OMIN 277400

Question 4

Which enzymes are involved?

Accepted Answer

methylmalonyl-CoA mutase, methionine synthase, inability of the cell to convert Cbl to both of its active forms (MeCbl, AdoCbl)

Disease	METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, cblC TYPE
Synonym	VITAMIN B12 METABOLIC DEFECT WITH METHYLMALONICACIDEMIA AND HOMOCYSTINURIA
OMIM	277400 OMIM = Online Mendelian Inheritance of Men
Orphanet	79282
Protein (UniProt)	methylmalonyl-CoA mutase, methionine synthase, inability of the cell to convert Cbl to both of its active forms (MeCbl, AdoCbl)
Gene locus	1p34.1
ICD	E72.1
Summary	rare (1:100.000, >550 cases) autosomal recessive mutation in the MMACHC gene Methylmalonic aciduria and homocystinuria, cblC type is the most common inborn error of vitamin B(12) (cobalamin) metabolism [Lerner-Ellis JP 2006, De Simone L 2018]. partial CblC-type MMA can onset with severe metabolic aHUS [Chen M et al. 2017]
Laboratory findings	Betaine normal/inc (urine) Homocysteine inc (plasma) Methylmalonic acid inc (urine) Hemoglobine normal/dec (blood) Homocysteine inc (urine) Methionine normal/dec (plasma) Protein inc (urine)
Symptoms	anemia neurological deterioration glossitis atrial septal defect behavior, abnormal or bizarre, confusion behavior, self-mutilating or destructive cardiac involvement, cardiac defects cardiomyopathy cerebral atrophy dementia developmental delay extrapyramidal signs failure to thrive feeding difficulties, poor feeding heart involvement Hemolytic-uremic-syndrome hydrocephalus hypotonia impaired visual acuity liver involvement or dysfunction low birthweight (small for gestational age) maculopathy megaloblastic anemia nystagmus psychosis retinopathy seizures small for gestational age (SGA), intrauterine growth retardation (IUGR) stomatitis Amino acids, plasma ataxia diarrhea early death Encephalopathic crisis, acute hematuria hemolysis hydrops fetalis lethargy, drowsiness, apathy mental retardation metabolic acidosis microcephaly (<2 SD for age) neutropenia (decreased neutrophils) onset, adolescent onset, adulthood onset, childhood onset, fetus onset, infancy onset, neonatal onset, variable age Organic acids, urine pulmonary hypertension renal failure, acute/chronic retinal or macular degeneration skin defects thromboembolism thrombopenia, thrombocytopenia vomiting