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Amish microcephaly: Long-term survival and biochemical characterization
Victoria Mok Siu1, Suzanne Ratko, Asuri N Prasad
1Department of Pediatrics, University of Western Ontario, London, Ontario, Canada.
American Journal of Medical Genetics. Part A
|June 29, 2010
Summary
Amish microcephaly (MCPHA) is a metabolic disorder causing severe congenital microcephaly. This study identifies a new patient and suggests persistent lactic acidemia may be a more consistent finding than alpha-ketoglutaric aciduria.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Amish microcephaly (MCPHA) is a rare metabolic disorder.
- Previously linked to SLC25A19 mutations and alpha-ketoglutaric aciduria.
- Characterized by severe infantile lethal congenital microcephaly.
Observation:
- A male patient with MCPHA from Ontario, Canada, with Amish ancestry is presented.
- Ultrasound revealed microcephaly at 21 weeks gestation.
- Facial appearance and brain MRI showed characteristic MCPHA features, including agenesis of the corpus callosum and spinal dysraphic state.
Findings:
- Urine alpha-ketoglutaric acid levels varied, being normal at birth and during crisis but elevated during metabolic stability.
- Severe lactic acidosis occurred during metabolic crises, responding to a high-fat diet.
- The patient exhibits severe microcephaly and profound developmental delay at age 7.
Implications:
- SLC25A19 transports deoxynucleotides and thiamine pyrophosphate (TPP).
- MCPHA phenotype may result from reduced activity of TPP-dependent mitochondrial enzymes.
- Persistent lactic acidemia may be a more common biochemical marker than alpha-ketoglutaric aciduria.
- Consider MCPHA in severe congenital microcephaly, especially with CNS malformations.
