Microcephaly, Amish type (MCPHA), also known as thiamine metabolism dysfunction syndrome 3 (THMD3), is a lethal, autosomal recessive condition characterized by severe congenital microcephaly, elevated levels of alpha-ketoglutarate in the urine, and premature death. This disorder has been observed in Old Order Amish families. Patients have a homozygous point mutation in SLC25A19 that encodes the mitochondrial TPP transporter. TPP, the activated form of thiamine, is an essential cofactor of three thiamine-dependent mitochondrial enzymes. Thiamine metabolism dysfunction syndrome 4 (THMD4) is an allelic disorder with a milder phenotype. THMD4 is characterized by bilateral striatal degeneration and progressive polyneuropathy.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
05 Endocrine, nutritional or metabolic diseases
Metabolic disorders
Disorders of metabolite absorption or transport
5C63 Disorders of vitamin or non-protein cofactor absorption or transport
H00990 Microcephaly, Amish type
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD20 Syndromes with central nervous system anomalies as a major feature
H00990 Microcephaly, Amish type
