Search Our Scientific Publications & Authors

Am J Med Genet A 2022 May 23;188(5):1443-1447. Epub 2022 Jan 23.

Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Liver transplantation (LT) has been used for many years as a therapeutic option for certain inborn errors of metabolism (IEMs). Here we present one institution's 27 years of experience with LT in IEMs. Our objective is to assess the outcomes of IEM patients who have undergone LT, which we hypothesize to be generally successful for prevention of metabolic decompensation. Read More

Orphanet J Rare Dis 2020 06 19;15(1):154. Epub 2020 Jun 19.

National Clinical Research Centre for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, 95# Yong-an Road, Xi Cheng District, Beijing, 100050, China.

Background: Patients with isolated methylmalonic acidemia (MMA) usually experience recurrent episodes of acute metabolic decompensation or metabolic stroke, require frequent hospitalization, and have a relatively high mortality rate. The aim of our study was to assess factors predicting the in-hospital death of pediatric patients with isolated MMA. We performed a retrospective study using data from the Hospital Quality Monitoring System, a national inpatient database in China collected from 2013 to 2017. Read More

JIMD Rep 2020 Jan 22;51(1):89-104. Epub 2020 Jan 22.

Department of Internal Medicine, Erasmus University Medical Center Center for Lysosomal and Metabolic Disease Rotterdam The Netherlands.

Introduction: New neurological symptoms in methylmalonic acidemia (MMA) patients after liver and/or kidney transplantation (LKT) are often described as metabolic stroke-like-events. Since calcineurin inhibitors (CNIs) are a well-known cause of new neurological symptoms in non-MMA transplanted patients, we investigated the incidence of CNI-induced neurotoxicity including posterior reversible encephalopathy syndrome (PRES) in post-transplanted MMA patients.

Methods: We report the two MMA patients treated with LKT in our center. Read More

Mol Genet Metab 2019 12 17;128(4):444-451. Epub 2019 Oct 17.

Children's National Rare Disease Institute, Children's National Health System, Washington DC 20010, United States. Electronic address:

Methylmalonic acidemia (MMA) is a propionate pathway disorder caused by dysfunction of the mitochondrial enzyme methylmalonyl-CoA mutase (MMUT). MMUT catalyzes the conversion of methylmalonyl-CoA to succinyl-CoA, an anaplerotic reaction which feeds into the tricarboxylic acid (TCA) cycle. As part of the pathological mechanisms of MMA, previous studies have suggested there is decreased TCA activity due to a "toxic inhibition" of TCA cycle enzymes by MMA related metabolites, in addition to reduced anaplerosis. Read More

Int J Mol Sci 2019 May 29;20(11). Epub 2019 May 29.

Department of Neurology, Karolinska University Hospital, 141 86 Stockholm, Sweden.

Methylmalonic aciduria (MMA-uria) is seen in several inborn errors of metabolism (IEM) affecting intracellular cobalamin pathways. Methylmalonyl-CoA epimerase (MCE) is an enzyme involved in the mitochondrial cobalamin-dependent pathway generating succinyl-CoA. Homozygous mutations in the corresponding gene have been shown in children to cause MCE deficiency with isolated MMA-uria and a variable clinical phenotype. Read More

Front Pediatr 2019 21;7:87. Epub 2019 Mar 21.

Intensive Care Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

MMA is a rare autosomal recessive disorder with the manifestation of recurrent and severe episodes of acute metabolic decompensation or a variety of long-term complications that require timely treatment. While conventional long-term medical and dietary management cannot prevent rapid progression of conditions in patients with severe complications, LT, or CKLT has become an option. We reviewed the literature for MMA patients undergoing LT/CKLT published since 2006, and data on metabolic decompensation status, protein dietary, neurological damage, renal insufficiency, and developmental delay before and after transplantations were compared to evaluate the clinical value of the procedure in the treatment of MMA. Read More

Mol Genet Metab 2018 11 24;125(3):235-240. Epub 2018 Aug 24.

Center for Neuroscience, Children Neuroscience, Medical System, George Washington University, Washington, DC, United States. Electronic address:

Background: Continuous EEG studies demonstrate that neonates with seizures due to cerebral pathology, such as hypoxia ischemia, exhibit predominantly electrographic seizures (i.e. those only detected with EEG because they lack clinical features). Read More

AJNR Am J Neuroradiol 2015 Jan 4;36(1):194-201. Epub 2014 Sep 4.

Genetics and Molecular Biology Branch (J.L.S., I.M., C.P.V.).

Background: Bilateral infarcts confined to the globus pallidus are unusual and occur in conjunction with only a few disorders, including isolated methylmalonic acidemia, a heterogeneous inborn error of metabolism. On the basis of neuroradiographic features of metabolic strokes observed in a large cohort of patients with methylmalonic acidemia, we have devised a staging system for methylmalonic acidemia-related globus pallidus infarcts.

Materials And Methods: Forty patients with isolated methylmalonic acidemia and neurologic symptoms underwent clinical brain MR imaging studies, which included 3D-T1WI. Read More

Mov Disord 2014 Jun 21;29(7):870. Epub 2014 Apr 21.

Centro de Medicina Genómica y Metabolismo, Fundación Cardiovascular de Colombia, Colombia; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, USA.

J Pediatr 2011 Nov 23;159(5):862-4. Epub 2011 Jul 23.

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Methylmalonic acidemia (MMA) is a heterogeneous disorder, with onset from infancy to adulthood and varying degrees of organ involvement and severity. Cardiac disease is a known lethal complication of other organic acidemias, but has not been associated with MMA. We identified 3 patients with MMA and cardiac disease. Read More

Expert Rev Neurother 2008 Nov;8(11):1731-41

Department of Neurology, University of South Florida College of Medicine, Tampa, FL 33606, USA.

The association of genetic factors and cerebral infarction (CI) has long been established. A positive family history alone is a recognized risk factor for CI and vascular events in general. However, there are certain inherited conditions that further increase the risk of stroke. Read More

Am J Transplant 2007 Dec 1;7(12):2782-7. Epub 2007 Oct 1.

Department of Transplant Surgery, National Center for Child Health and Development, Tokyo, Japan.

Application of liver transplantation to methylmalonic acidemia (MMAemia) is controversial because MMAemia is caused by a systemic defect of methylmalonyl-CoA mutase. The clinical courses of seven pediatric patients with MMAemia undergoing living donor liver transplantation (LDLT) were reviewed. Serum and urinary methylmalonic acid (MMA) levels were found to be significantly decreased after LDLT, whereas serum and urinary MMA levels did not return to normal in any patient. Read More

J Pediatr 2002 Feb;140(2):261-3

Liver Unit, Birmingham Children's Hospital, United Kingdom.

It is believed that liver transplantation may improve the outcome of early onset methylmalonic acidemia. We report a case of methylmalonic acidemia in which successful liver transplantation in infancy failed to prevent neurologic damage caused by a metabolic stroke. Read More

J Pediatr 1989 Sep;115(3):499-500

J Pediatr 1988 Dec;113(6):1022-7

Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia.

We report four patients with methylmalonic acidemia who developed acute extrapyramidal disease after metabolic decompensation. The neurologic findings resulted from bilateral destruction of the globus pallidus with variable involvement of the internal capsules. This complication was unrelated to a specific gene defect responsible for methylmalonic acidemia or to cyanocobalamin administration. Read More