[MIM 617 384]

See also phenylKetonuria and tetrahydrobiopterin deficiency

Very rare: < 1/106 . Autosomal recessive transmission of a mutation of the DNAJC12 gene (10q21.3). This mutation should be looked  for in cases of hyperphenylalaninemia without mutation of the phenylalanine hydroxylase gene nor abnormality of the tetrahydropterin metabolism (BH4). DNAJC12 codes for a chaperone protein (from the DNA heat shock protein family) contributing to the correct deployment of the phenylalanine hydroxylase.

Clinical diagnostic criteria: hyperphenylalaninemia responding to the administration of BH4 with low dopamine and serotonin levels in  the CSF.

Without treatment, the phenotype is highly variable: moderate autistic disorders, hyperactivity with attention deficit, severe intellectual deficit, dystonia, parkinsonism.

Treatment: diet, BH4, L-dopa/carbidopa and 5-hydroxytryptophan as in case of tetrahydrobiopterin deficiency.

Anesthetic implications:

see tetrahydrobiopterin deficiency

References:

-        Blau  N, Aurora Martinez A, Hoffmann GF, Thöny B. 
DNAJC12 deficiency: A new strategy in the diagnosis of hyperphenylalaninemias.
Mol Genet Metab 2018;123(1):1-5.

-        Opladen T, Lopez-Laso E, Cortes-Saladelafont E, Pearson TS, Sivri HS et al.
Consensus guidelines for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies.
Orphanet J Rare Diseases 2020; 15:126

Updated: August 2020