Mild clinical and biochemical phenotype in two patients with PMM2-CDG (congenital disorder of glycosylation Ia).
Phosphomannomutase 2 deficiency (PMM2-CDG) patients may present as mild phenotypes, with the cerebellum frequently involved. In those cases, false-negative results in screening may occur when applying conventional biochemical procedures. Our aim was to report two patients with a diagnosis of PMM2-CDG presenting with mild clinical phenotype. Patient 1-at 9 months of age, she presented with just psychomotor delay, tremor, hypotonia, and slight lipodystrophy. Patient 2-she presented at 8 months of age with psychomotor delay, hand stereotypes, hypotonia, convergent bilateral strabismus, and tremor but no lipodystrophy. Routine biochemical parameters including blood count, clotting factors, proteins, and thyroid hormone were normal in both cases. Cranial MRI evidenced mild cerebellar atrophy with moderate vermis hypoplasia. In case 1, sialotransferrin pattern showed very slightly increased disialotransferrin with no asialotransferrin, and in case 2, the transferrin pattern was impaired in the first study but nearly normal in the second. Nevertheless, in all the samples, quantification of the patterns obtained by capillary zone electrophoresis analysis gave results out of the control range. High residual PMM2 activity was observed in both cases and the genetic analysis showed that patient 1 was heterozygous for c.722G>C (p.C241S) and c.368G>A (p.R123Q) mutations, and patient 2 showed the c.722G>C and the c.470T>C (p.F157S) mutations in the PMM2 gene. We would like to stress the importance of the use of sensitive semiquantitative methods of screening for CDG in order to achieve early identification of patients with mild phenotypes. Intentional tremor was an atypical but remarkable clinical feature in both cases, and the global cerebellar atrophy with vermis hypoplasia reinforced the early clinical suspicion of a PMM2-CDG disease.
Clinical Biochemistry, Hospital Sant Joan de Déu, Barcelona, Spain.
M
M
Casado
M M
MM
O'Callaghan
R
R
Montero
C
C
Pérez-Cerda
B
B
Pérez
P
P
Briones
E
E
Quintana
J
J
Muchart
A
A
Aracil
M
M
Pineda
R
R
Artuch
D001921:Brain / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D018981:Congenital Disorders of Glycosylation / Q000235:genetics / Q000378:metabolism* / Q000523:psychology*; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000209:etiology / Q000523:psychology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020233:Gait Disorders, Neurologic / Q000209:etiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007223:Infant; D007525:Isoelectric Focusing; D008060:Lipodystrophy / Q000209:etiology; D008279:Magnetic Resonance Imaging; D009460:Neurologic Examination; D010641:Phenotype; D017875:Phosphotransferases (Phosphomutases) / Q000172:deficiency; D014168:Transferrin / Q000235:genetics / Q000378:metabolism
D014168:Transferrin; D004247:DNA; D017875:Phosphotransferases (Phosphomutases)