Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy
Abstract Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive mitochondrial disorder characterized by cumulative and progressive gastrointestinal and neurological findings. This retrospective observational study, aimed to explore the time of presentation, diagnosis...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-09-01
|
| Series: | JIMD Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jmd2.12315 |
| _version_ | 1811209812309966848 |
|---|---|
| author | Sema Kalkan Uçar Havva Yazıcı Ebru Canda Esra Er Fatma Derya Bulut Cenk Eraslan Hüseyin Onay Bridget Elizabeth Bax Mahmut Çoker |
| author_facet | Sema Kalkan Uçar Havva Yazıcı Ebru Canda Esra Er Fatma Derya Bulut Cenk Eraslan Hüseyin Onay Bridget Elizabeth Bax Mahmut Çoker |
| author_sort | Sema Kalkan Uçar |
| collection | DOAJ |
| description | Abstract Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive mitochondrial disorder characterized by cumulative and progressive gastrointestinal and neurological findings. This retrospective observational study, aimed to explore the time of presentation, diagnosis and clinical follow‐up of 13 patients with a confirmed MNGIE disease of Mediterranean origin. The mean age of symptom onset was 7 years (6 months−21 years) and the average diagnosis age was 15.4 years ±8.4. Four of 13 patients (30%) died before 30 years at the mean age of 19.7 years ±6.8. Cachexia and gastrointestinal symptoms were observed in all patients (100%). The mean body mass index standard deviation score at diagnosis was 4.8 ± 2.8. At least three subocclusive episodes were presented in patients who died in last year of their life. The main neurological symptom found in most patients was peripheral neuropathy (92%). Ten patients (77%) had leukoencephalopathy and the remaining three patients without were under 10 years of age. The new homozygous “Mediterranean” TYMP mutation, p.P131L (c.392 C > T) was associated with an early presentation and poor prognosis in nine patients (69%) from five separates families. Based on the observations from this Mediterranean MNGIE cohort, we propose that the unexplained abdominal pain combined with cachexia is an indicator of MNGIE. High‐platelet counts and nerve conduction studies may be supportive laboratory findings and the frequent subocclusive episodes could be a negative prognostic factor for mortality. Finally, the homozygous p.P131L (c.392 C > T) mutation could be associated with rapid progressive disease with poor prognosis. |
| first_indexed | 2024-04-12T04:46:20Z |
| format | Article |
| id | doaj.art-fa1e7a6b696a40c6a9e89adca314e9cc |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-04-12T04:46:20Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-fa1e7a6b696a40c6a9e89adca314e9cc2022-12-22T03:47:30ZengWileyJIMD Reports2192-83122022-09-0163548449310.1002/jmd2.12315Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathySema Kalkan Uçar0Havva Yazıcı1Ebru Canda2Esra Er3Fatma Derya Bulut4Cenk Eraslan5Hüseyin Onay6Bridget Elizabeth Bax7Mahmut Çoker8Department of Pediatrics, Division of Metabolism and Nutrition Ege University Medical Faculty Izmir TurkeyDepartment of Pediatrics, Division of Metabolism and Nutrition Ege University Medical Faculty Izmir TurkeyDepartment of Pediatrics, Division of Metabolism and Nutrition Ege University Medical Faculty Izmir TurkeyDepartment of Pediatrics, Division of Metabolism and Nutrition Ege University Medical Faculty Izmir TurkeyDepartment of Pediatrics, Division of Metabolism and Nutrition Çukurova University Medical Faculty Adana TurkeyDepartment of Radiology, Division of Neuroradiology Ege University Medical Faculty Bornova TurkeyDepartment of Genetics Ege University Medical Faculty Izmir TurkeyInstitute of Molecular and Clinical Sciences St George's University of London London UKDepartment of Pediatrics, Division of Metabolism and Nutrition Ege University Medical Faculty Izmir TurkeyAbstract Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive mitochondrial disorder characterized by cumulative and progressive gastrointestinal and neurological findings. This retrospective observational study, aimed to explore the time of presentation, diagnosis and clinical follow‐up of 13 patients with a confirmed MNGIE disease of Mediterranean origin. The mean age of symptom onset was 7 years (6 months−21 years) and the average diagnosis age was 15.4 years ±8.4. Four of 13 patients (30%) died before 30 years at the mean age of 19.7 years ±6.8. Cachexia and gastrointestinal symptoms were observed in all patients (100%). The mean body mass index standard deviation score at diagnosis was 4.8 ± 2.8. At least three subocclusive episodes were presented in patients who died in last year of their life. The main neurological symptom found in most patients was peripheral neuropathy (92%). Ten patients (77%) had leukoencephalopathy and the remaining three patients without were under 10 years of age. The new homozygous “Mediterranean” TYMP mutation, p.P131L (c.392 C > T) was associated with an early presentation and poor prognosis in nine patients (69%) from five separates families. Based on the observations from this Mediterranean MNGIE cohort, we propose that the unexplained abdominal pain combined with cachexia is an indicator of MNGIE. High‐platelet counts and nerve conduction studies may be supportive laboratory findings and the frequent subocclusive episodes could be a negative prognostic factor for mortality. Finally, the homozygous p.P131L (c.392 C > T) mutation could be associated with rapid progressive disease with poor prognosis.https://doi.org/10.1002/jmd2.12315clinical overviewmitochondrial neurogastrointestinal encephalomyopathythymidine phosphorylase |
| spellingShingle | Sema Kalkan Uçar Havva Yazıcı Ebru Canda Esra Er Fatma Derya Bulut Cenk Eraslan Hüseyin Onay Bridget Elizabeth Bax Mahmut Çoker Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy JIMD Reports clinical overview mitochondrial neurogastrointestinal encephalomyopathy thymidine phosphorylase |
| title | Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy |
| title_full | Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy |
| title_fullStr | Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy |
| title_full_unstemmed | Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy |
| title_short | Clinical spectrum of early onset “Mediterranean” (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy |
| title_sort | clinical spectrum of early onset mediterranean homozygous p p131l mutation mitochondrial neurogastrointestinal encephalomyopathy |
| topic | clinical overview mitochondrial neurogastrointestinal encephalomyopathy thymidine phosphorylase |
| url | https://doi.org/10.1002/jmd2.12315 |
| work_keys_str_mv | AT semakalkanucar clinicalspectrumofearlyonsetmediterraneanhomozygouspp131lmutationmitochondrialneurogastrointestinalencephalomyopathy AT havvayazıcı clinicalspectrumofearlyonsetmediterraneanhomozygouspp131lmutationmitochondrialneurogastrointestinalencephalomyopathy AT ebrucanda clinicalspectrumofearlyonsetmediterraneanhomozygouspp131lmutationmitochondrialneurogastrointestinalencephalomyopathy AT esraer clinicalspectrumofearlyonsetmediterraneanhomozygouspp131lmutationmitochondrialneurogastrointestinalencephalomyopathy AT fatmaderyabulut clinicalspectrumofearlyonsetmediterraneanhomozygouspp131lmutationmitochondrialneurogastrointestinalencephalomyopathy AT cenkeraslan clinicalspectrumofearlyonsetmediterraneanhomozygouspp131lmutationmitochondrialneurogastrointestinalencephalomyopathy AT huseyinonay clinicalspectrumofearlyonsetmediterraneanhomozygouspp131lmutationmitochondrialneurogastrointestinalencephalomyopathy AT bridgetelizabethbax clinicalspectrumofearlyonsetmediterraneanhomozygouspp131lmutationmitochondrialneurogastrointestinalencephalomyopathy AT mahmutcoker clinicalspectrumofearlyonsetmediterraneanhomozygouspp131lmutationmitochondrialneurogastrointestinalencephalomyopathy |