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Methylmalonic acidemia with homocystinuria is an inherited disorder in which the body is unable to properly process protein building blocks (amino acids), certain fats (lipids), and a waxy fat-like substance called cholesterol. When the condition begins early in life, affected individuals typically have failure to thrive, IUGR, pallor, hypotonia, seizures. Most infants and children with this condition have microcephaly, delayed development and intellectual disability¹ . Less common features of the condition include eye problems and a blood disorder called megaloblastic anemia. When methylmalonic acidemia with homocystinuria begins in adolescence or adulthood, the signs and symptoms usually include psychiatric changes and cognitive problems ² .
In addition, these individuals can begin to lose previously acquired mental and movement abilities, resulting in a decline in school or work performance, difficulty controlling movements, memory problems, speech difficulties, a decline in intellectual function (dementia), or an extreme lack of energy (lethargy). The most common form of the condition, called methylmalonic acidemia with homocystinuria, cblC type, is estimated to affect 1 in 200,000 newborns worldwide.Methylmalonic acidemia with homocystinuria can be caused by mutations in one of several genes: MMACHC, MMADHC, LMBRD1, ABCD4, or HCFC1. Methylmalonic acidemia with homocystinuria is usually inherited in an autosomal recessive pattern ³ .
A 3-years Male Child Born Of Third-degree Consanguineous Marriage Presented With:
|Test Name||Sample Type||Method|
|Whole Exome Sequencing||2-4 EDTA Blood||Next Generation Sequencing||Mean coverage of 80-100X coverage. Target coverage 200X|
Whole Exome Sequencing: A homozygous likely pathogenic variant was found in the MMACHC gene (Table.1)
|Gene & Transcript||Variant||Location||Zygosity||Disorder (OMIM)||Inheritance|
|Exon 3||Homozygous||Methylmalonic aciduria &
Homocystinuria CblC type (277400)
|Mr. Nadir Aman||Genetic Counselor||Compilation|
|Ms. Vineeta Singh||Vice President-Scientific Affairs||Exome Analysis|