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Malonic Acidemia

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Immediate steps after receiving a positive newborn screen for malonic acidemia

Other Names

MA
Malonic aciduria
Malonyl-CoA decarboxylase deficiency
Malonyl-coenzyme A decarboxylase deficiency
MLYCDD

ICD-10 Coding

P09.1, Abnormal newborn screening for inborn errors of metabolism

Disorder Category

Organic acidemia

Screening

Abnormal Finding

Elevated C3-DC (acylcarnitine)
Malonic acid in urine organic acids

Tested By

Tandem mass spectrometry (MS/MS); sensitivity=NA; specificity=NA

Description

Insufficient malonyl-CoA decarboxylase enzyme activity inhibits fatty acid regulation, resulting in the accumulation of malonic acid and its derivatives in the blood and urine. Although malonic aciduria presents most classically with developmental delay, epilepsy, dystonia, hypoglycemia, metabolic acidosis, and white matter lesions on brain MRI, it has a variable phenotype. Treatment involves carnitine supplementation, a low-fat diet supplemented with medium-chain triglycerides, and avoidance of metabolic stress/fasting. [Wightman: 2003]

Clinical Characteristics

With treatment, many of the sequelae may be prevented or ameliorated. However, the evidence is scarce due to insufficient patient numbers and no clear treatment guidelines. Developmental delays and hypotonia can be seen even with optimal treatment and without any episode of decompensation. Therapy is supportive, helping to promote normal growth and development.
Without treatment, disability is likely to progress as episodes of hypoglycemia and metabolic acidosis may lead to further respiratory distress, developmental delays, hypotonia, seizures, and cardiomyopathy. Significant variability in severity has been described with this condition, ranging from severe symptom onset within the first few weeks of life to some that have been found incidentally by newborn screening and have seemingly remained asymptomatic. Symptoms in some cases may be triggered by metabolic stress like prolonged fasting or infectious illnesses.
Initial symptoms/signs may include:
  • Respiratory distress
  • Hypotonia
  • Cardiomyopathy
  • Seizures
  • Vomiting
  • Poor feeding
  • Diarrhea
  • Lethargy
  • Hypoglycemia
  • Metabolic acidosis
More commonly, malonic acidemia presents in infancy or later childhood. Signs/symptoms include:
  • Developmental delay
  • Seizures
  • Failure to thrive
  • Hypotonia

Incidence

As many as 55 cases have been reported in medical literature. [Zhao: 2023]

Inheritance

Autosomal recessive

Primary Care Management

Next Steps After a Positive Screen

  • Contact the family and evaluate the infant for vomiting, poor feeding, lethargy, and ketonuria.
  • Provide emergency treatment/referral for evidence of hypoglycemia, acidosis, or seizures.
  • Consult with a pediatric metabolic specialist the same day (or as soon as possible).
  • Initiate confirmatory/diagnostic testing as recommended by the specialist (see below).
  • Provide the family with basic information about malonic acidemia and its management.

Confirming the Diagnosis

  • To confirm the diagnosis, work with Newborn Screening Services (see OH providers [1]).
  • Quantitative plasma acylcarnitine profile (C3-DC is elevated[MN1] ) and urine organic acids (elevated malonic acid)
  • If results are consistent with malonic acidemia, obtain molecular genetic testing.

If the Diagnosis is Confirmed

  • For evaluation and ongoing collaborative management, consult Medical Genetics (see OH providers [0]).
  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill.
  • Support implementation and maintenance of a high-carbohydrate, low-fat diet with medium-chain triglyceride supplements. Oral L-carnitine supplementation is often indicated.
  • Promptly treat infections, fever, and gastroenteritis with IV fluids containing glucose and admit to hospital.
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
  • Provide initial consultation and ongoing collaboration, particularly for dietary management.
  • Refer for genetic counseling for the family: Genetic Testing and Counseling (see OH providers [1]).

Resources

Information & Support

After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis - You Are Not Alone; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.

For Professionals

Malonic Aciduria (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.

For Parents and Patients

Malonic Aciduria (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Baby's First Test: Malonic Acidemia (Genetic Alliance)
Information about early signs, follow-up testing, treatment, accessing care, and expected outcomes. Provides links to support services.

Organic Acidemia Association (OAA)
A nonprofit organization that provides information, support, events, connections with other parents, a discussion board, and nutrition and recipe ideas.

Tools

ACT Sheet for Elevated C3-Acylcarnitine (ACMG) (PDF Document 347 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithm for Malonic Aciduria (Elevated C3-DC) (ACMG) (PDF Document 155 KB)
Resource for clinicians to help confirm diagnosis; American College of Medical Genetics.

Services for Patients & Families in Ohio (OH)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Studies

Malonic Aciduria (ClinicalTrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.

Helpful Articles

PubMed search for malonic aciduria in children

Footitt EJ, Stafford J, Dixon M, Burch M, Jakobs C, Salomons GS, Cleary MA.
Use of a long-chain triglyceride-restricted/medium-chain triglyceride-supplemented diet in a case of malonyl-CoA decarboxylase deficiency with cardiomyopathy.
J Inherit Metab Dis. 2010. PubMed abstract

Authors & Reviewers

Initial publication: March 2007; last update/revision: November 2023
Current Authors and Reviewers:
Author: Meera Nagarajan, MD
Senior Author: Brian J. Shayota, MD, MPH
Reviewer: Nancy C. Rose, MD
Authoring history
2023: update: Meera Nagarajan, MDA; Brian J. Shayota, MD, MPHSA
2017: update: Nicola Longo, MD, Ph.D.A
2011: first version: Nicola Longo, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

Footitt EJ, Stafford J, Dixon M, Burch M, Jakobs C, Salomons GS, Cleary MA.
Use of a long-chain triglyceride-restricted/medium-chain triglyceride-supplemented diet in a case of malonyl-CoA decarboxylase deficiency with cardiomyopathy.
J Inherit Metab Dis. 2010. PubMed abstract

Wightman PJ, Santer R, Ribes A, Dougherty F, McGill N, Thorburn DR, FitzPatrick DR.
MLYCD mutation analysis: evidence for protein mistargeting as a cause of MLYCD deficiency.
Hum Mutat. 2003;22(4):288-300. PubMed abstract

Zhao C, Peng H, Jiang N, Liu Y, Chen Y, Liu J, Guo Q, Wu Z, Wang L.
A case of malonyl coenzyme A decarboxylase deficiency with novel mutations and literature review.
Front Pediatr. 2023;11:1133134. PubMed abstract / Full Text