HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients
3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is a rare inborn error of leucine degradation and ketone body synthesis, caused by homozygous or compound heterozygous disease-causing variants in HMGCL. To understand the natural history of this disease, we reviewed the biochemi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.880464/full |
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| author | Majid Alfadhel Majid Alfadhel Basma Abadel Hind Almaghthawi Muhammad Umair Zuhair Rahbeeni Eissa Faqeih Mohammed Almannai Ali Alasmari Mohammed Saleh Wafaa Eyaid Wafaa Eyaid Ahmed Alfares Ahmed Alfares Fuad Al Mutairi Fuad Al Mutairi |
| author_facet | Majid Alfadhel Majid Alfadhel Basma Abadel Hind Almaghthawi Muhammad Umair Zuhair Rahbeeni Eissa Faqeih Mohammed Almannai Ali Alasmari Mohammed Saleh Wafaa Eyaid Wafaa Eyaid Ahmed Alfares Ahmed Alfares Fuad Al Mutairi Fuad Al Mutairi |
| author_sort | Majid Alfadhel |
| collection | DOAJ |
| description | 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is a rare inborn error of leucine degradation and ketone body synthesis, caused by homozygous or compound heterozygous disease-causing variants in HMGCL. To understand the natural history of this disease, we reviewed the biochemical, clinical, and molecular data of 62 patients from 54 different families with confirmed HMG-CoA lyase deficiency (HMGCLD) diagnosis from Saudi Arabia. The majority of the affected individuals were symptomatic. At initial diagnosis, 38 patients (61.29%) presented with hypoglycemia and 49 patients (79.03%) developed metabolic acidosis. In 27 patients (43.54%), the disorder manifested in the neonatal period, mostly within the first days of life, while 35 (56.45%) patients were diagnosed within the first year of life or beyond. All the patients were alive and developed long-term neurological complications during data collection, which may significantly influence their quality of life. Common neurological findings include seizures 17/62 (27.41%), hypotonic 3/62 (4.83%), speech delay 7/62 (11.29%), hyperactivity 4/62 (4.83%), developmental delay 6/62 (9.677%), learning disability 15/62 (24.14%), and ataxic gate 1/62 (1.612%). An MRI of the brain exhibited nonspecific periventricular and deep white matter hyperintense signal changes in 16 patients (25.80%) and cerebral atrophy was found in one (1/62; 1.612%) patient. We identified a founder variant [c.122G>A; p.(Arg41Gln)] in 48 affected individuals (77.41%) in the HMGCL gene. This is the largest cohort of HMGCLD patients reported from Saudi Arabia, signifying this disorder as a likely life-threatening disease, with a high prevalence in the region. Our findings suggest that diagnosis at an early stage with careful dietary management may avoid metabolic crises. |
| first_indexed | 2024-04-14T04:54:35Z |
| format | Article |
| id | doaj.art-1a76d79b4d1d4643b0a6276b01de203b |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-14T04:54:35Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-1a76d79b4d1d4643b0a6276b01de203b2022-12-22T02:11:11ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-05-011310.3389/fgene.2022.880464880464HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi PatientsMajid Alfadhel0Majid Alfadhel1Basma Abadel2Hind Almaghthawi3Muhammad Umair4Zuhair Rahbeeni5Eissa Faqeih6Mohammed Almannai7Ali Alasmari8Mohammed Saleh9Wafaa Eyaid10Wafaa Eyaid11Ahmed Alfares12Ahmed Alfares13Fuad Al Mutairi14Fuad Al Mutairi15Genetics and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City MNG-HA, Riyadh, Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi ArabiaGenetics and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City MNG-HA, Riyadh, Saudi ArabiaGenetics and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City MNG-HA, Riyadh, Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi ArabiaMedical Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaSection of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi ArabiaGenetics and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City MNG-HA, Riyadh, Saudi ArabiaSection of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi ArabiaSection of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi ArabiaGenetics and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City MNG-HA, Riyadh, Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi ArabiaDepartment of Pediatrics, College of Medicine, Qassim University, Qassim, Saudi ArabiaDivision of Translational Pathology, Department of Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi ArabiaGenetics and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City MNG-HA, Riyadh, Saudi ArabiaMedical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is a rare inborn error of leucine degradation and ketone body synthesis, caused by homozygous or compound heterozygous disease-causing variants in HMGCL. To understand the natural history of this disease, we reviewed the biochemical, clinical, and molecular data of 62 patients from 54 different families with confirmed HMG-CoA lyase deficiency (HMGCLD) diagnosis from Saudi Arabia. The majority of the affected individuals were symptomatic. At initial diagnosis, 38 patients (61.29%) presented with hypoglycemia and 49 patients (79.03%) developed metabolic acidosis. In 27 patients (43.54%), the disorder manifested in the neonatal period, mostly within the first days of life, while 35 (56.45%) patients were diagnosed within the first year of life or beyond. All the patients were alive and developed long-term neurological complications during data collection, which may significantly influence their quality of life. Common neurological findings include seizures 17/62 (27.41%), hypotonic 3/62 (4.83%), speech delay 7/62 (11.29%), hyperactivity 4/62 (4.83%), developmental delay 6/62 (9.677%), learning disability 15/62 (24.14%), and ataxic gate 1/62 (1.612%). An MRI of the brain exhibited nonspecific periventricular and deep white matter hyperintense signal changes in 16 patients (25.80%) and cerebral atrophy was found in one (1/62; 1.612%) patient. We identified a founder variant [c.122G>A; p.(Arg41Gln)] in 48 affected individuals (77.41%) in the HMGCL gene. This is the largest cohort of HMGCLD patients reported from Saudi Arabia, signifying this disorder as a likely life-threatening disease, with a high prevalence in the region. Our findings suggest that diagnosis at an early stage with careful dietary management may avoid metabolic crises.https://www.frontiersin.org/articles/10.3389/fgene.2022.880464/fullKetogenesishypoglycemiaHMG-CoA lyaseSaudi Arabiaketone body synthesisacidosis |
| spellingShingle | Majid Alfadhel Majid Alfadhel Basma Abadel Hind Almaghthawi Muhammad Umair Zuhair Rahbeeni Eissa Faqeih Mohammed Almannai Ali Alasmari Mohammed Saleh Wafaa Eyaid Wafaa Eyaid Ahmed Alfares Ahmed Alfares Fuad Al Mutairi Fuad Al Mutairi HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients Frontiers in Genetics Ketogenesis hypoglycemia HMG-CoA lyase Saudi Arabia ketone body synthesis acidosis |
| title | HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients |
| title_full | HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients |
| title_fullStr | HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients |
| title_full_unstemmed | HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients |
| title_short | HMG-CoA Lyase Deficiency: A Retrospective Study of 62 Saudi Patients |
| title_sort | hmg coa lyase deficiency a retrospective study of 62 saudi patients |
| topic | Ketogenesis hypoglycemia HMG-CoA lyase Saudi Arabia ketone body synthesis acidosis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.880464/full |
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