Molecular Genetic Analysis of a Patient with Moderate Hemophilia A and Psychomotor Developmental Delay

Hemophilia A is an inherited X-linked recessive trait and because of deficiency or complete absence of coagulation factor VIII patients present with increased bleeding symptoms (especially joint bleeding). The severity and frequency of bleeding episodes depend on the factor VIII activity and manifest as mild, moderate and severe hemophilia A.

Here we present a case of a boy with moderate hemophilia A. The factor VIII activity (one stage method) was 3.5% (normal range: 60–100%) and the PTT (partial thromboplastin time) was prolonged to 56 s (normal 28–40 s). At 1 month of age, the patient underwent surgery for pylorus stenosis in the presence of plasmatic factor VIII. Von Willebrand Factor antigen (VWF) and the activity of factors IX, XI and XII were within normal limits. The other blood parameters (blood smear, other coagulation parameters, C-reactive protein) were normal.

Interestingly, the patient later additionally presented with psychomotor developmental retardation. The details of the developmental pattern of the patient are shown in [Table 1]. The patient also showed uncoordinated movement and had the tendency to hit himself. However, he did not demonstrate ataxia. MRI scan which was performed for correlation of behavior to anatomy was normal.

Table 1 Developmental feature with respect to the age of the patient.

Age of patient	Developmental delay
15–16 months	– Able to walk, but unstable walking
2.5 years	– Difficulty remembering names of objects from a picture book – Unable to identify a picture
3 years	Language delay: – Spoke only a few words (eg mother, father, car) – Unable to form sentences Fine motor deficiency: – Difficulty performing tasks like putting beads on a string
4.5 years	– Displayed restlessness – Failed to understand simple instructions – Showed no response to requests
6 years	Behavioural perception problems: – Displayed autistic features and avoided eye contact

The family history revealed that the patient’s biological mother had low school performance and social/behavioral problems. She had spent part of her life living on the streets and gave birth at the age of 17 years. She also demonstrated moderate sensorineural deficiency (hearing problems). The maternal grandparents of the patient were consanguineous. 3 of the patient’s relatives suffered from mental retardation, delayed speech development and social/behavioural problems ([Fig. 1]).

Fig. 1 Pedigree tree for the patient and his family. The consanguineous maternal grandparents of the patient are shown. The patient and his siblings are shown in the order of birth (patient: eldest).