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Cardiomyopathy-hypotonia-lactic acidosis syndrome(MPCD)

MedGen UID:
324373
Concept ID:
C1835845
Disease or Syndrome
Synonyms: Mitochondrial phosphate carrier deficiency; MPCD
SNOMED CT: Mitochondrial phosphate carrier deficiency (1187515001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SLC25A3 (12q23.1)
 
Monarch Initiative: MONDO:0012557
OMIM®: 610773
Orphanet: ORPHA91130

Definition

Mitochondrial phosphate carrier deficiency (MPCD) is an autosomal recessive disorder characterized by onset of cardiorespiratory insufficiency soon after birth. Patients usually require intervention in the neonatal period. The disorder may result in death in infancy, although those that survive have stabilization or amelioration of symptoms with age. Most affected individuals have hypotonia, delayed motor development, and exercise intolerance, but cognitive development is normal. Laboratory studies typically show increased serum lactate, although this may not be present. Muscle biopsy shows abnormal mitochondria and lipid accumulation. There is phenotypic variability likely depending on the location of the mutation (summary by Bhoj et al., 2015). [from OMIM]

Clinical features

From HPO
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
Cyanosis
MedGen UID:
1189
Concept ID:
C0010520
Sign or Symptom
Bluish discoloration of the skin and mucosa due to poor circulation or inadequate oxygenation of arterial or capillary blood.
Abnormal mitochondrial shape
MedGen UID:
868649
Concept ID:
C4023050
Finding
An anomaly in the surface contour of mitochondria.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCardiomyopathy-hypotonia-lactic acidosis syndrome
Follow this link to review classifications for Cardiomyopathy-hypotonia-lactic acidosis syndrome in Orphanet.

Professional guidelines

PubMed

Barski L, Golbets E, Jotkowitz A, Schwarzfuchs D
Eur J Intern Med 2023 Nov;117:38-44. Epub 2023 Jul 5 doi: 10.1016/j.ejim.2023.07.005. PMID: 37419787
Bering J, DiBaise JK
Nutr Clin Pract 2023 May;38 Suppl 1:S46-S58. doi: 10.1002/ncp.10978. PMID: 37115034
El-Hattab AW, Adesina AM, Jones J, Scaglia F
Mol Genet Metab 2015 Sep-Oct;116(1-2):4-12. Epub 2015 Jun 15 doi: 10.1016/j.ymgme.2015.06.004. PMID: 26095523

Recent clinical studies

Etiology

Barski L, Golbets E, Jotkowitz A, Schwarzfuchs D
Eur J Intern Med 2023 Nov;117:38-44. Epub 2023 Jul 5 doi: 10.1016/j.ejim.2023.07.005. PMID: 37419787
Khunti K, Del Prato S, Mathieu C, Kahn SE, Gabbay RA, Buse JB
Diabetes Care 2021 Dec;44(12):2645-2655. Epub 2021 Oct 8 doi: 10.2337/dc21-1318. PMID: 34625431Free PMC Article
Bagga A, Sinha A
Indian J Pediatr 2020 Sep;87(9):733-744. Epub 2020 Jun 26 doi: 10.1007/s12098-020-03318-8. PMID: 32591997
Karslioglu French E, Donihi AC, Korytkowski MT
BMJ 2019 May 29;365:l1114. doi: 10.1136/bmj.l1114. PMID: 31142480
Alexander RT, Bitzan M
Pediatr Clin North Am 2019 Feb;66(1):135-157. doi: 10.1016/j.pcl.2018.08.011. PMID: 30454739

Diagnosis

Hopkins PM, Girard T, Dalay S, Jenkins B, Thacker A, Patteril M, McGrady E
Anaesthesia 2021 May;76(5):655-664. Epub 2021 Jan 5 doi: 10.1111/anae.15317. PMID: 33399225
Pohanka M
Biomed Res Int 2020;2020:3419034. Epub 2020 Jun 17 doi: 10.1155/2020/3419034. PMID: 32685468Free PMC Article
Bagga A, Sinha A
Indian J Pediatr 2020 Sep;87(9):733-744. Epub 2020 Jun 26 doi: 10.1007/s12098-020-03318-8. PMID: 32591997
Alexander RT, Bitzan M
Pediatr Clin North Am 2019 Feb;66(1):135-157. doi: 10.1016/j.pcl.2018.08.011. PMID: 30454739
Wagner CA, Mohebbi N
J Nephrol 2010 Nov-Dec;23 Suppl 16:S165-9. PMID: 21170875

Therapy

Barski L, Golbets E, Jotkowitz A, Schwarzfuchs D
Eur J Intern Med 2023 Nov;117:38-44. Epub 2023 Jul 5 doi: 10.1016/j.ejim.2023.07.005. PMID: 37419787
Hopkins PM, Girard T, Dalay S, Jenkins B, Thacker A, Patteril M, McGrady E
Anaesthesia 2021 May;76(5):655-664. Epub 2021 Jan 5 doi: 10.1111/anae.15317. PMID: 33399225
Chand R, Swenson ER, Goldfarb DS
Curr Opin Nephrol Hypertens 2021 Mar 1;30(2):223-230. doi: 10.1097/MNH.0000000000000687. PMID: 33395037
Smith ZR, Horng M, Rech MA
Pharmacotherapy 2019 Sep;39(9):946-963. Epub 2019 Aug 29 doi: 10.1002/phar.2316. PMID: 31361914
Kam PC, Cardone D
Anaesthesia 2007 Jul;62(7):690-701. doi: 10.1111/j.1365-2044.2007.05055.x. PMID: 17567345

Prognosis

Alves CAPF, Zandifar A, Peterson JT, Tara SZ, Ganetzky R, Viaene AN, Andronikou S, Falk MJ, Vossough A, Goldstein AC
AJNR Am J Neuroradiol 2023 May;44(5):602-610. Epub 2023 Apr 6 doi: 10.3174/ajnr.A7837. PMID: 37024306Free PMC Article
Khunti K, Del Prato S, Mathieu C, Kahn SE, Gabbay RA, Buse JB
Diabetes Care 2021 Dec;44(12):2645-2655. Epub 2021 Oct 8 doi: 10.2337/dc21-1318. PMID: 34625431Free PMC Article
Napoleão A, Fernandes L, Miranda C, Marum AP
Nutrients 2021 Apr 15;13(4) doi: 10.3390/nu13041302. PMID: 33920973Free PMC Article
Alexander RT, Bitzan M
Pediatr Clin North Am 2019 Feb;66(1):135-157. doi: 10.1016/j.pcl.2018.08.011. PMID: 30454739
Allison MG, McCurdy MT
Emerg Med Clin North Am 2014 May;32(2):293-301. Epub 2014 Feb 19 doi: 10.1016/j.emc.2013.12.002. PMID: 24766933

Clinical prediction guides

Khunti K, Del Prato S, Mathieu C, Kahn SE, Gabbay RA, Buse JB
Diabetes Care 2021 Dec;44(12):2645-2655. Epub 2021 Oct 8 doi: 10.2337/dc21-1318. PMID: 34625431Free PMC Article
Napoleão A, Fernandes L, Miranda C, Marum AP
Nutrients 2021 Apr 15;13(4) doi: 10.3390/nu13041302. PMID: 33920973Free PMC Article
Hanna RM, Ghobry L, Wassef O, Rhee CM, Kalantar-Zadeh K
Blood Purif 2020;49(1-2):202-211. Epub 2019 Dec 18 doi: 10.1159/000504240. PMID: 31851983
El-Hattab AW, Adesina AM, Jones J, Scaglia F
Mol Genet Metab 2015 Sep-Oct;116(1-2):4-12. Epub 2015 Jun 15 doi: 10.1016/j.ymgme.2015.06.004. PMID: 26095523
Krejs GJ
Am J Med 1987 May 29;82(5B):37-48. doi: 10.1016/0002-9343(87)90425-6. PMID: 3035922

Recent systematic reviews

Aldafas R, Crabtree T, Alkharaiji M, Vinogradova Y, Idris I
Age Ageing 2024 Jan 2;53(1) doi: 10.1093/ageing/afad254. PMID: 38287703Free PMC Article
Davis JD, Sanchez-Ramos L, McKinney JA, Lin L, Kaunitz AM
Am J Obstet Gynecol 2023 May;228(5S):S1179-S1191.e19. Epub 2023 Mar 18 doi: 10.1016/j.ajog.2022.07.047. PMID: 37164492
Smith ZR, Horng M, Rech MA
Pharmacotherapy 2019 Sep;39(9):946-963. Epub 2019 Aug 29 doi: 10.1002/phar.2316. PMID: 31361914
Bianchetti DGAM, Amelio GS, Lava SAG, Bianchetti MG, Simonetti GD, Agostoni C, Fossali EF, Milani GP
Pediatr Nephrol 2018 Apr;33(4):673-681. Epub 2017 Dec 7 doi: 10.1007/s00467-017-3844-8. PMID: 29218437
Ramos-Casals M, Brito-Zerón P, Seror R, Bootsma H, Bowman SJ, Dörner T, Gottenberg JE, Mariette X, Theander E, Bombardieri S, De Vita S, Mandl T, Ng WF, Kruize A, Tzioufas A, Vitali C; EULAR Sjögren Syndrome Task Force
Rheumatology (Oxford) 2015 Dec;54(12):2230-8. Epub 2015 Jul 31 doi: 10.1093/rheumatology/kev200. PMID: 26231345Free PMC Article

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