Demographic and clinical features of glutaric acidemia type 1; a high frequency among isolates in Upper Egypt

Zaki, Osama K.; Elabd, Heba Salah Abd-Elkhalek; Ragheb, Shaimaa Gad; Ghoraba, Dina A.; Elghawaby, Ahmed Essam

doi:10.1016/j.ejmhg.2014.01.001

Cited by 4 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This incidence is comparable to or higher than other metabolic disorders that are currently screened for by either selective or NBS methods. For example, glutaric aciduria type 1 has a birth prevalence of ~1 in 100,000, propionic aciduria ~1 in 100,000 – 150,000 and beta-ketothiolase deficiency has an estimated birth prevalence that ranges from 1 in 232,000 – <1 in a million [25–27]. Our results suggest that HIBCH may not be as rare as previously thought supporting the need for greater awareness of and appropriate diagnostic work-up for HIBCH deficiency.…”

Section: Discussionmentioning

confidence: 54%

Successful diagnosis of HIBCH deficiency from exome sequencing and positive retrospective analysis of newborn screening cards in two siblings presenting with Leigh's disease

Stiles

Ferdinandusse

Besse

et al. 2015

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

Purpose 3-hydroxyisobutryl-CoA hydrolase (HIBCH) deficiency is a rare disorder of valine metabolism. We present a family with the oldest reported subjects with HIBCH deficiency and provide support that HIBCH deficiency should be included in the differential for elevated hydroxy-C4-carnitine in newborn screening (NBS). Methods Whole exome sequencing (WES) was performed on one affected sibling. HIBCH enzymatic activity was measured in patient fibroblasts. Acylcarnitines were measured by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Disease incidence was estimated using a cohort of 61,434 individuals. Results Two siblings presented with infantile-onset, progressive neurodegenerative disease. WES identified a novel homozygous variant in HIBCH c.196C>T; p.Arg66Trp. HIBCH enzymatic activity was significantly reduced in patients’ fibroblasts. Acylcarnitine analysis showed elevated hydroxy-C4-carnitine in blood spots of both affected siblings, including in their NBS cards, while plasma acylcarnitines were normal. Estimates show HIBCH deficiency incidence as high as 1 in ~130,000 individuals. Conclusion We describe a novel family with HIBCH deficiency at the biochemical, enzymatic and molecular level. Disease incidence estimates indicate HIBCH deficiency may be under-diagnosed. This together with the elevated hydroxy-C4-carnitine found in the retrospective analysis of our patient’s NBS cards suggests that this disorder could be screened by NBS programs and should be added to the differential diagnosis for elevated hydroxy-C4-carnitine which is already measured in most NBS programs using MS/MS.

show abstract

Section: Discussionmentioning

confidence: 54%

Successful diagnosis of HIBCH deficiency from exome sequencing and positive retrospective analysis of newborn screening cards in two siblings presenting with Leigh's disease

Stiles

Ferdinandusse

Besse

et al. 2015

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

show abstract

“…Glutaric acidemia (GA) was detected in 40/320 (12.5%): by elevation of glutarylcarnitine (C5DC) in dried blood spot samples. The diagnosis was confirmed by the detection of elevated peaks of urinary glutaric and 3-OH glutaric acids by GC/MS, which are the diagnostic metabolites according to the findings of the researchers [22,27,28].…”

Section: Discussionmentioning

confidence: 82%

“…Glutaric acidemia type 1 (GA-1) is caused by the defect in functional glutaryl-CoA dehydrogenase (GCDH) activity, an important enzyme in the catabolism of l-tryptophan, l-lysine, and l-hydroxylysine, leads to the accumulation of glutaric acid, 3-hydroxyglutaric acid (3-OH-GA), and occasionally glutaconic acid in the different body fluids [28]. Propionic acidemia (PA) was detected in 32/320 (10%) by elevations of C3 and the ratio of C3:C2 in dried blood spot samples.…”

Section: Discussionmentioning

confidence: 99%

Inherited metabolic disorders in a cohort of Egyptian children

Abdelsattar

Obada

El-Hawy

et al. 2022

Egypt Liver Journal

Self Cite

View full text Add to dashboard Cite

Background Inborn errors of metabolism (IEMs) represent a special challenge in pediatric practice. Despite the unquestionable clinical significance of newborn screening, it just offers a snapshot of an extremely minor subgroup of metabolic disorders. So, it is crucial to use multiple techniques for accurate diagnosis of a wider spectrum of IEMs early in infancy to prevent overwhelming irreversible neurological complications in a cohort of high-risk Egyptian pediatrics. This study included four thousand and eighty suspected IEMs patients. They were referred to the Chromatography Unit, Clinical Biochemistry and Molecular Diagnostics Laboratories, National Liver Institute (NLI) for laboratory assessment in the period from March 2016 to November 2020. Separation of amino acids and acylcarnitines using tandem mass spectrometry (LC/MS) and organic acids using gas chromatography mass spectrometry (GC/MS) was done. Results Three hundred and twenty (320/4080, 7.8%) patients were diagnosed with IEMs. The following disorders were identified: organic acidopathies—200 (62.5%) including methylmalonic acidemia (MMA) (48/320, 15%), glutaric academia (GA) (40/320, 12, 5%), propionic acidemia (PA), (32/320, 10%), isovaleric acidemia (IVA) (40/320, 12.5%), methylcrotonyl glyceinuria (16/320, 5%), and orotic acidemia (24/320, 7.5%); amino acidopathies—80 (25%) including maple syrup urine disease (MSUD) (32/320, 10%), phenylketonuria (24/320, 7.5%), homocystinuria (16/320, 5%), and nonketotic hyperglycinemia (8/320, 2.5%) in addition to fatty acid disorders (FAO): 24 (7.5%) and lactic academia (LA), 16 (5%). Conclusion Early detection of IEMs by rapid non-invasive techniques. LC/MS and GC/MS. is a crucial process for early diagnosis of different types of IEMs to install therapeutic clue in a group of high-risk Egyptian pediatrics for proper treatment and better outcome

show abstract

“…occurring during febrile illness or other catabolic states) like acute or chronic onset of MD in infants, gait abnormalities or (truncal) muscular hypotonia. 5,45,[88][89][90][91][92][93][94][95][96][97] Individuals with late-onset form may present with unspecific neurologic signs like polyneuropathy, incontinence, headache, earlyonset dementia, epilepsy or tremor. 21,40,44,57 Neuroradiologic abnormalities occur frequently in all patients and are summarised in Table S3.…”

Section: Targeted Diagnostic Work-up Due To Suggestive Clinical Bioch...mentioning

confidence: 99%

“…Beside macrocephaly, suggestive clinical signs comprise acute neurologic manifestations (e.g. occurring during febrile illness or other catabolic states) like acute or chronic onset of MD in infants, gait abnormalities or (truncal) muscular hypotonia 5,45,88–97 . Individuals with late‐onset form may present with unspecific neurologic signs like polyneuropathy, incontinence, headache, early‐onset dementia, epilepsy or tremor 21,40,44,57 .…”

Section: Diagnostic Proceduresmentioning

confidence: 99%

Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision

Boy

Mühlhausen²,

Maier

et al. 2022

J of Inher Metab Disea

View full text Add to dashboard Cite

Glutaric aciduria type 1 is a rare inherited neurometabolic disorder of lysine metabolism caused by pathogenic gene variations in GCDH (cytogenic location: 19p13.13), resulting in deficiency of mitochondrial glutaryl-CoA dehydrogenase (GCDH) and, consequently, accumulation of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid and glutarylcarnitine detectable by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Depending on residual GCDH activity, biochemical high and low excreting phenotypes have been defined. Most untreated individuals present with acute onset of striatal damage before age 3 (to 6) years, precipitated by infectious diseases, fever or surgery, resulting in irreversible, mostly dystonic movement disorder with limited life expectancy. In some patients, striatal damage develops insidiously. In recent years, the clinical phenotype has been extended by the finding of extrastriatal abnormalities and cognitive dysfunction, preferably in the high excreter group, as well as chronic kidney failure. Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and For affiliation refer to page 29

show abstract

Demographic and clinical features of glutaric acidemia type 1; a high frequency among isolates in Upper Egypt

Cited by 4 publications

References 12 publications

Successful diagnosis of HIBCH deficiency from exome sequencing and positive retrospective analysis of newborn screening cards in two siblings presenting with Leigh's disease

Successful diagnosis of HIBCH deficiency from exome sequencing and positive retrospective analysis of newborn screening cards in two siblings presenting with Leigh's disease

Inherited metabolic disorders in a cohort of Egyptian children

Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: Third revision

Contact Info

Product

Resources

About