Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options

Wasim, Muhammad; Awan, Fazli Rabbi; Khan, Haq Nawaz; Tawab, Abdul; Iqbal, Mazhar; Ayesha, Hina

doi:10.1007/s10528-017-9825-6

Cited by 49 publications

(37 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The establishment of newborn screening programs has successfully decreased the prevalence of homocystinuria and other aminoacidopathies. Yet, the majority of these disorders arise due to consanguineous marriages [48]. The consanguinity rate reached 40% among first cousins in the Middle East and up to 60% in intermarriages between relatives.…”

Section: The Prevalence Of Cbs and Associated Mutations In The Mena Rmentioning

confidence: 99%

The Spectrum of Mutations of Homocystinuria in the MENA Region

Al-Sadeq

Nasrallah

2020

Genes

View full text Add to dashboard Cite

Homocystinuria is an inborn error of metabolism due to the deficiency in cystathionine beta-synthase (CBS) enzyme activity. It leads to the elevation of both homocysteine and methionine levels in the blood and urine. Consequently, this build-up could lead to several complications such as nearsightedness, dislocated eye lenses, a variety of psychiatric and behavioral disorders, as well as vascular system complications. The prevalence of homocystinuria is around 1/200,000 births worldwide. However, its prevalence in the Gulf region, notably Qatar, is exceptionally high and reached 1:1800. To date, more than 191 pathogenic CBS mutations have been documented. The majority of these mutations were identified in Caucasians of European ancestry, whereas only a few mutations from African-Americans or Asians were reported. Approximately 87% of all CBS mutations are missense and do not target the CBS catalytic site, but rather result in unstable misfolded proteins lacking the normal biological function, designating them for degradation. The early detection of homocystinuria along with low protein and methionine-restricted diet is the best treatment approach for all types of homocystinuria patients. Yet, less than 50% of affected individuals show a significant reduction in plasma homocysteine levels after treatment. Patients who fail to lower the elevated homocysteine levels, through high protein-restricted diet or by B6 and folic acid supplements, are at higher risk for cardiovascular diseases, neurodegenerative diseases, neural tube defects, and other severe clinical complications. This review aims to examine the mutations spectrum of the CBS gene, the disease management, as well as the current and potential treatment approaches with a greater emphasis on studies reported in the Middle East and North Africa (MENA) region.

show abstract

Section: The Prevalence Of Cbs and Associated Mutations In The Mena Rmentioning

confidence: 99%

The Spectrum of Mutations of Homocystinuria in the MENA Region

Al-Sadeq

Nasrallah

2020

Genes

View full text Add to dashboard Cite

show abstract

“…MSUD was first reported by Menkes et al (2) in 1954. MSUD is a rare autosomal recessive disorder with an incidence of 1 in 185,000 children worldwide (3). However, the incidence in some regions is expected to be higher due to an increased rate of consanguineous marriages (4).…”

Section: Introductionmentioning

confidence: 99%

Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease

et al. 2019

View full text Add to dashboard Cite

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by mutations in genes that encode subunits of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. Impairment of the BCKD complex results in an abnormal accumulation of branched-chain amino acids and their corresponding branched-chain keto acids in the blood and cerebrospinal fluid, which are neurovirulent and may become life-threatening. An 11-day-old boy was admitted to the hospital with paroxysmal spasticity of lower extremities. Of note, his 10-year-old sister presented similar symptoms during the neonatal period, and her condition was diagnosed as MSUD when she was 1.5 years old. Genetic screening was performed, and the boy and his sister exhibited two novel compound heterozygous mutations in the branched chain keto acid dehydrogenase E1 subunit β (BCKDHB) gene: A substitution from guanine to adenine in the coding region at position 1,076 (c.1,076G>A) in exon 10 and a deletion of a thymine at position 705 (c.705delT) in exon 6. The missense mutation c.1076G>A results in an amino acid substitution from arginine to lysine at position 359 (p.Arg359Lys), whereas the mutation c.705delT results in the replacement of a cysteine at position 235 with a stop codon (p.Cys235Ter). Neither of the BCKDHB alleles in the compound heterozygote patients is able to generate normal E1β subunits, resulting in a possible impairment of the activity of the BCKD complex. In the present study, it was hypothesized that the two novel heterozygous mutations in the BCKDHB gene found in the Chinese family may be responsible for the phenotype of the two siblings with MSUD.

show abstract

“…Dentro de las categorías en que se clasifican los EIM se encuentran las alteraciones fisiológicas de los aminoácidos, denominadas aminoacidopatías. Una de las maneras en que se pueden detectar es mediante ensayos genéticos (Wasim, et. al.…”

Section: Manejo Nutricional Actual De La Pku En Niñosunclassified

Manejo nutricional actual de la Phenylketonuria PKU en niños

Ríos

2020

View full text Add to dashboard Cite

La fenilcetonuria es una enfermedad metabólica hereditaria que requiere de un tratamiento nutricional de por vida el cual pretende mantener los niveles de PHE en sangre bajos para evitar daño neurológico, pero además debe proveer un adecuado aporte de proteína y energía, así como mantener un adecuado estado nutricional desde el momento del diagnóstico (López-Mejía, Vergara-Vázquez & Guillén-López, 2019). Debido a esto, se pretendió evidenciar el tratamiento nutricional brindado a pacientes pediátricos con PKU según datos recientes sobre el tema con la presente revisión bibliográfica.

show abstract

Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options

Cited by 49 publications

References 67 publications

The Spectrum of Mutations of Homocystinuria in the MENA Region

The Spectrum of Mutations of Homocystinuria in the MENA Region

Paroxysmal spasticity of lower extremities as the initial symptom in two siblings with maple syrup urine disease

Manejo nutricional actual de la Phenylketonuria PKU en niños

Contact Info

Product

Resources

About