Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2017

Open Access 01-12-2017 | Letter to the Editor

Combined methylmalonic acidemia and homocysteinemia presenting predominantly with late-onset diffuse lung disease: a case series of four patients

Authors: Jinrong Liu, Yun Peng, Nan Zhou, Xiaorong Liu, Qun Meng, Hui Xu, Shunying Zhao

Published in: Orphanet Journal of Rare Diseases | Issue 1/2017

Login to get access

Abstract

Combined methylmalonic acidemia (MMA) and homocysteinemia are a group of autosomal recessive disorders caused by inborn errors of cobalamin metabolism, including CblC, D, F, and J, with cblC being the most common subtype. The clinical manifestations of combined MMA and homocysteinemia vary, but typically include neurologic, developmental and hematologic abnormalities.
We report 4 children with combined MMA and homocysteinemia who presented predominantly with late-onset diffuse lung diseases (DLD). Of these, 3 accompanied by pulmonary arterial hypertension (PAH), 1 accompanied by hypertension, and 2 accompanied by renal thrombotic microangiopathy (TMA), which was confirmed by renal biopsy. This confirms combined MMA and homocysteinemia should be considered in the differential diagnosis of DLD with or without PAH or renal TMA.
Literature
1.
Arroliga AC, Sandur S, Jacobsen DW, Tewari S, Mustafa M, Mascha EJ, et al. Association between hyperhomocysteinemia and primary pulmonary hypertension. Respir Med. 2003;97(7):825–9.CrossRefPubMed
2.
Wuillemin WA, Solenthaler M. Hyperhomocysteinemia: a risk factor for arterial and venous thrombosis. Vasa. 1999;28(3):151–5.CrossRefPubMed
3.
Profitlich L, Kirmse B, Wasserstein MP, Diaz G, Srivastava S. Resolution of cor pulmonale after medical management in a patient with cblC-type methylmalonic aciduria and homocystinuria: a case report. Cases J. 2009;2:8603.CrossRefPubMedPubMedCentral
4.
Gunduz M, Ekici F, Ozaydin E, Ceylaner S, Perez B. Reversible pulmonary arterial hypertension in cobalamin-dependent cobalamin C disease due to a novel mutation in the MMACHC gene. Eur J Pediatr. 2014;173(12):1707–10.CrossRefPubMed
5.
Iodice FG, Di Chiara L, Boenzi S, Aiello C, Monti L, Cogo P, et al. Cobalamin C defect presenting with isolated pulmonary hypertension. Pediatrics. 2013;132(1):e248–51.CrossRefPubMed
6.
Komhoff M, Roofthooft MT, Westra D, Teertstra TK, Losito A, van de Kar NC, et al. Combined pulmonary hypertension and renal thrombotic microangiopathy in cobalamin C deficiency. Pediatrics. 2013;132(2):e540–44.CrossRefPubMed
7.
Grangé S, Bekri S, Artaud-Macari E, Francois A, Girault C, Poitou AL, et al. Adult-onset renal thrombotic microangiopathy and pulmonary arterial hypertension in cobalamin C deficiency. Lancet. 2015;386(9997):1011–2.CrossRefPubMed
8.
George JN. Cobalamin C, deficiency-associated thrombotic microangiopathy: uncommon or unrecognised? Lancet. 2015;386(9997):1012.CrossRefPubMed
9.
Qi YH, Qi JG, Liu YP, Yan H, Liu XQ, Zhang X, et al. Clinical analysis and follow-up study of cardiavascular system involvement in 10 children withmethylmalonic aciduria combined with hyperhomocysteinemia. Zhongguo Dang Dai Er Ke Za Zhi. 2015;17(9):965–70.PubMed
10.
Lerner-Ellis JP, Tirone JC, Pawelek PD, Doré C, Atkinson JL, Watkins D, et al. Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. Nat Genet. 2006;38(1):93–100.CrossRefPubMed
11.
Huemer M, Scholl-Bürgi S, Hadaya K, Kern I, Beer R, Seppi K, et al. Three new cases of late onset cblC defect and review of the literature illustrating when to consider inborn errors of metabolism beyond infancy. Orphanet J Rare Dis. 2014;9:161.CrossRefPubMedPubMedCentral
12.
Wang F, Han L, Yang Y, Gu X, Ye J, Qiu W, et al. Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China. J Inherit Metab Dis. 2010;33 Suppl 3:S435–42.CrossRefPubMed
13.
Liu MY, Yang YL, Chang YC, Chiang SH, Lin SP, Han LS, et al. Mutation spectrum of MMACHC in Chinese patients with combined methylmalonic aciduria and homocystinuria. J Hum Genet. 2010;55(9):621–6.CrossRefPubMed
14.
Li QL, Song WQ, Peng XX, Liu XR, He LJ, Fu LB. Clinical characteristics of hemolytic uremic syndrome secondary to cobalamin C disorder in Chinesechildren. World J Pediatr. 2015;11(3):276–80.CrossRefPubMed
15.
Beck BB, van Spronsen F, Diepstra A, Berger RM, Kömhoff M. Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity. Pediatr Nephrol. 2016 Jun 11. [Epub ahead of print]
16.
Bouts AH, Roofthooft MT, Salomons GS, Davin JC. CD46-associated atypical hemolytic uremic syndrome with uncommon course caused by cblC deficiency. Pediatr Nephrol. 2010;25(12):2547–8.CrossRefPubMedPubMedCentral
17.
De Bie I, Nizard SD, Mitchell GA. Fetal dilated cardiomyopathy: an unsuspected presentation of methylmalonic aciduria and hyperhomocystinuria, cblC type. Prenat Diagn. 2009;29(3):266–70.CrossRefPubMed
18.
Brandstetter Y, Weinhouse E, Splaingard ML, Tang TT. Cor pulmonale as a complication of methylmalonic acidemia and homocystinuria (Cbl-C type). Am J Med Genet. 1990;36(2):167–71.CrossRefPubMed
19.
Agarwal R, Feldman GL, Poulik J, Stockton DW, Sood BG. Methylmalonic acidemia presenting as persistent pulmonary hypertension of the newborn. J Neonatal Perinatal Med. 2014;7(3):247–51.PubMed
20.
Baumgartner ER, Wick H, Maurer R, Egli N, Steinmann B. Congenital defect in intracellular cobalamin metabolism resulting in homocysteinuria and methylmalonic aciduria. I. Case report and histopathology. Helv Paediatr Acta. 1979;34(5):465–82.PubMed
21.
Russo P, Doyon J, Sonsino E, Ogier H, Saudubray JM. A congenital anomaly of vitamin B12 metabolism: a study of three cases. Hum Pathol. 1992;23(5):504–12.CrossRefPubMed
Metadata
Title
Combined methylmalonic acidemia and homocysteinemia presenting predominantly with late-onset diffuse lung disease: a case series of four patients
Authors
Jinrong Liu
Yun Peng
Nan Zhou
Xiaorong Liu
Qun Meng
Hui Xu
Shunying Zhao
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2017
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-017-0610-8

Other articles of this Issue 1/2017

Orphanet Journal of Rare Diseases 1/2017 Go to the issue

Research

Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family

Research

Indirect estimation of the prevalence of spinal muscular atrophy Type I, II, and III in the United States

Letter to the Editor

Expanding the clinical and mutational spectrum of B4GALT7-spondylodysplastic Ehlers-Danlos syndrome

Research

Pain and quality of life evaluation in patients with localized epidermolysis bullosa simplex

Research

STUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations

Research

TuberOus SClerosis registry to increase disease Awareness (TOSCA) – baseline data on 2093 patients