Fasting Tolerance in MCADD-infants

Summary

MCAD deficiency (MCADD; #OMIM 201450) is the most common inherited disorder of mitochondrial fatty acid oxidation. Already before the introduction of population newborn bloodspot screening (NBS), large phenotypic heterogeneity was observed between MCADD-patients, ranging between deceased patients and asymptomatic subjects. Most clinically ascertained patients were homozygous for the common c.985A\>G ACADM mutation. After NBS, newborns with novel ACADM-genotypes have been identified and subjects can be classified as either severe/classical or mild/variant MCADD-patients.

Dietary management guidelines are based on expert opinion, limited experimental data summarized in one retrospective study on fasting tolerance in 35 MCADD patients. Interestingly, data are absent from fasting tolerance in MCADD patients between 0-6 months of age. These guidelines cause parental stress, especially for young patients. Moreover, the guidelines do not take into account the heterogeneity between patients, including the classification between severe versus mild MCADD-patients. The investigators question whether at least a subset of the MCADD-patients is overtreated with these guidelines.

Therefore, the investigators propose this pilot-study on fasting tolerance in 10 subjects with severe MCADD and 10 subjects with mild MCADD at the ages of two and six months. Differences between subsets of MCADD-patients will be studied longitudinally by both traditional metabolic parameters and unbiassed metabolomics, lipidomics and proteomics approach. This project will substantiate current management guidelines and aims to identify new (prognostic) biomarkers.

Conditions

• Mcad Deficiency

Interventions

OTHER

Fasting test

The included infants will be fasted according to local standardized procedures at the University Medical Centre Groningen. Fasting will take place under hourly blood glucose monitoring and bedside supervision by an experienced, dedicated pediatric nurse, in collaboration with a metabolic pediatrician, who will be available to attend the patient instantly. Furthermore, on request of parent(s) or guardian(s), a continuous blood glucose monitoring device can be used during the study visits. During study visit 1, at two months of life, fasting will be continued for maximally eight hours. During study visit 2, at six months of life, fasting will be continued for maximally twelve hours. Fasting will be ended prematurely in the following events: * blood glucose concentration drops \< 3.6 mmol/L; * the child shows symptoms/signs of a low blood glucose concentration; * patients parent(s) or guardian(s) request end of fast.

Sponsors & Collaborators

• University Medical Center Groningen

  lead OTHER

Principal Investigators

• Terry Derks, MD, PhD · Consultant pediatrician metabolic diseases

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

2 Months

Max Age

6 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-05-15

Primary Completion

2024-01-31

Completion

2024-01-31

Countries

• Netherlands

Study Locations